METHOD AND MARKERS FOR THE DIAGNOSIS OF RENAL DISEASES

METHODE ET MARQUEURS DE DIAGNOSTIC DES MALADIES RENALES

English Abstract

The present invention relates to means and methods for the diagnosis of a
renal disease,
particularly to differential diagnosis. Renal diseases of particular interest
in the context of
the invention are IgA-nephropathy, membranous glomerulonephritis (MGN),
minimal-change-disease (MCD), focal segemental glomerulosclerosis (FSGS), and
diabetic
nephropathy. Particularly, the method comprises (a) measuring the presence or
the absence
of a polypeptide marker in a urine sample, wherein the polypeptide marker is
selected from
the group of polypeptide markers shown in tables 1 to 22, and (b) comparing
the
probability of the presence of this marker in a disease patient to the
probability of the
presence of this marker in a control patient, wherein the individual
probabilities are as
indicated in the tables, and wherein (c1) if the probability of the presence
of this marker in
a disease patient is higher than the probability of the presence of this
marker in a control
patient, the presence of this marker is indicative for a higher probability of
having the
disease, or (c2) if the probability of the presence of this marker in a
disease patient is lower
than the probability of the presence of this marker in a control patient, the
absence of the
marker is indicative for a higher probability of having the disease.

Claims

Claims

1. Use of the presence of at least one polypeptide marker in a urine sample
for the
diagnosis of a renal disease, wherein the polypepgide marker is selected from
the
group of polypeptide markers as shown in tables 1 to 22.

2. The use according to claim 1, wherein the renal disease is chosen from the
group
consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

3. The use according to claim 1, wherein the renal disease is IgA-nephropathy.

4. The use according to claim 1, wherein diagnosis relates to differential
diagnosis.
between at least two diseases chosen from the group consisting of IgA-
nephropathy,
MGN, MCD, FSGS, and diabetic nephropathy.

5. The use according to any of claims 1 to 4, wherein the polypeptide marker
is selected
from the group of polypeptide markers as shown in tables 1 to 13.

6. The use according to claim 3, wherein the polypeptide marker is selected
from the
group of polypeptide markers as shown in tables 11 to 13.

7. A method for the diagnosis of a renal disease, the method comprising:
a) measuring the presence or the absence of a polypeptide marker in a urine
sample, wherein the polypeptide marker is selected from the group of
polypeptide markers shown in tables 1 to 22, and
b) comparing the probability of the presence of this marker in a disease
patient to
the probability of the presence of this marker in a control patient, wherein
c1) if the probability of the presence of this marker in a disease patient is
higher than
the probability of the presence of this marker in a control patient, the
presence of
this marker is indicative for a higher probability of having the disease
rather than
the control condition, or



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c2) if the probability of the presence of this marker in a disease patient is
lower than
the probability of the presence of this marker in a control patient, the
absence of
the marker is indicative for a higher probability of having the disease rather
than
the control condition.

8. The method according to claim 7, wherein the individual probabilities in
step b) are
as indicated in the tables.

9. The method according to any of claims 7 to 8, wherein the control
represents the
healthy condition.

10. The method according to any of claims 7 to 9, wherein the control
represents a renal
disease, particularly chosen from the group consisting of IgA-nephropathy,
MGN,
MCD, FSGS, and diabetic nephropathy.

11. The method according to any of claims 7 to 9, wherein the polypeptide
marker is
selected from the group of polypeptide markers shown in tables 11 to 13.

12. The method according to any of claims 7 to 11, wherein the method
comprises
detecting a plurality of the polypeptide markers, preferably at least 3, more
preferably at least 10, most preferably at least 50 of the polypeptide
markers.

13. The method according to any of claims 7 to 12, wherein ELISA, quantitative
Western Blot, radio-immuno-assay, surface plasmon resonance, array, gel
electrophoresis, capillary electrophoresis, gas phase ion spectrometry, or
mass
spectrometry is used for detecting the presence of the marker or markers.

14. The method according to any of claims 7 to 13, wherein the polypeptide
markers in.
the sample are separated by capillary electrophoresis. before measurement.

15. The method according to claim 14, wherein mass spectrometry is used for
detecting
the presence of the marker or markers.

16. Use of capillary electrophoresis-mass spectrometry for the diagnosis,
particularly
differential diagnosis, of a renal disease in vitro.



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17. The use according to claim 16, wherein the renal disease is selected from
the group
consisting of IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

18. Use of capillary electrophoresis-mass spectrometry for the differential
diagnosis
between at least two renal diseases selected from the group consisting of IgA-
nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.

Description

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mosaiques diagnostics and therapeutics AG July ~, 2004
M62 704CA BO/mei
Method and markers for the diagnosis of renal diseases
The present invention relates to the diagnosis, particularly differential
diagnosis, of renal
diseases.
IO
The number of patients presenting with renal diseases has been increasing in
the recent
years. Thus, renal diseases present an increasing problem to the health
system. Many renal
diseases are irreversible, therefore an early diagnosis and/or a differential
diagnosis of
renal diseases is important. Early diagnosis and a therapy precisely tailored
to each
particular disease could reduce the number of patients requiring dialysis and
could also
reduce the high cardiovascular risk of the patients.
Currently, precise diagnosis and/or differential diagnosis relies mostly on
kidney biopsies.
Although biopsies serve as the current "gold standard" in renal diagnostics,
biopsies have
2o the disadvantage of being invasive and therefore being conducted only on
selected patients.
Urine analysis is a different approach to diagnose renal diseases. However,
currently only
few parameters of urine are routinely measured, for example creatinin, urea,
albumin,
blood cells (such as leukocytes and erythrocytes), bacteria, sugar,
urobilinogen, bilirubin
and pH value. The diagnostic value of these analyses is limited, as they lack
sufficient
sensitivity and/or selectivity, particularly for differential diagnosis.
Several attempts have been made to analyze the proteins contained in urine.
V. Thongboonkerd et al. have used two-dimensional polyacrylarnide gel
electrophoresis
(2D-PAGE) in combination with matrix-assisted laser desorption ionization-time-
of flight
(MALDI-TOF) mass spectrometry followed by mass fingerprinting to investigate
normal
human urinary proteins. A total of 67 protein forms of 47 unique proteins was
. identified
(V. Thongboonkerd et al. (2001). Proteomic analysis of normal human urinary
proteins


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isolated by acetone precipitation or ultracentrifugation. Kidney
International, vol. 62, p.
1461- I 469).
C.S. Spahr et al. have digested the proteins contained in urine samples with
trypsin and
identified 751 peptides from 124 proteins by means of liquid chromatography-
tandem
mass spectrometry (C.S. Spahr et al. (2001). Towards defining the urinary
proteome using
liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated
tryptic
digest. Proteomics vol. 1, p. 93-107).
1o These studies relate only to healthy individuals. The studies have not
addressed the
question whether alterations in presence of urinary polypeptides can bewsed
for diagnosis
or differential diagnosis of renal diseases.
It has been proposed to use the presence or absence of polypeptides in urine
for the
diagnosis of membranous glomerulonephritis (MGN) (von Neuhoff et al. (2004).
Mass
Spectrometry for the Detection of Differentially Expressed Proteins: A
Comparison of
Surface-Enhanced Laser Desorption/Ionization and Capillary
Electrophoresis/Mass
Spectrometry. Rapid Communications in Mass Spectrometry, vol. 18: 149-156).
However,
samples of only 8 patients were used in the study, which was mainly concerned
with the
2o comparison of different analysis methods. The actual diagnostic value of
the markers has
remained unclear.
Consequently, there is need for a fast and simple methods and means for
diagnosis,
particularly differential diagnosis, of renal diseases.
Accordingly, the object the present invention is to provide methods and means
fox the
diagnosis of renal diseases, particularly for differential diagnosis of renal
diseases. It is an
particular object of the present invention to provide methods and means for
the diagnosis
and/or differential diagnosis of IgA-nephropathy, which is the most common
3o glomerulopathy.
According to a first aspect of the present invention, the problem is solved by
the use of the
presence of at least one polypeptide marker in a urine sample for the
diagnosis, preferably
the differential diagnosis, of a renal disease, wherein the polypeptide marker
is selected
from the group of polypeptide markers as shown in table 1 to 22.


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In the context of the present invention, it has been found that with the help
of the
polypeptide markers as shown in table 1 to 22 it is possible to reliably
diagnose or
differentially diagnose, respectively, different renal diseases.
The present invention has numerous advantages compared to the state of the
art. First, the
presence of the polypeptide markers according to the invention can be
determined in urine
samples. Therefore, there is no need to take biopsies. Thus, the present
invention allows a
simplified and fast diagnosis of renal diseases, allowing to screen patients
regularly for the
presence of renal diseases and to diagnose renal diseases at early stages.
Furthermore, the
1 o polypeptide markers according to the invention can be used for
differential diagnosis
between different renal diseases. The high number of markers identified
according to the
present invention allows to increase both specificity and sensitivity of
diagnosis as
compared to the use of only a single or a small number of markers. Also, the
present
invention provides methods which allow to measure said polypeptide markes
without the
use of specific ligands such as antibodies or aptamers.
The polypeptide markers as shown in the tables have been identified by a
method, named
capillary electrophoresis-mass spectrometry (CE-MS), which will be described
further
below. Furthermore, the method has been described in detail in von Neuhoff et
al. (2004)
2o (Mass Spectrometry for the Detection of Differentially Expressed Proteins:
A Comparison
of Surface-Enhanced Laser Desorption/Ionization and Capillary
Electrophoresis/Mass
Spectrometry. Rapid Communications in Mass Spectrometry, vol. 18: 149-156).
Starting
from the parameters defining the polypeptide markers, it is possible by
methods known in
the art to identify the sequence of the corresponding polypeptides and then to
synthesize or
produce the corresponding polypeptides, e.g. with the help of protein
synthesis or
expression of the corresponding gene in appropriate cells.
The markers are defined by there mass and their migration time in capillary
electrophoresis
(CE), particularly mass and their migration time obtained according to Example
1. It is
3o known that CE migration times can vary, typically in the range of 5 min,
more typically in
the range of 3 minutes. However, the sequence of markers being eluted is
typically the
same or very similar for each CE system applied. The system can be calibrated
by use of
polypeptides which are present in almost any urine sample, e.g. by the
polypeptides given
in tables 23 or 24. Furthermore, the polypeptides given in SEQ IZ? NO: 1 to
SEQ ID NO: 5
can serve for calibration.


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Variation of the masses between measurements or between different mass
spectrometers is
relatively small, typically it is in the range of plus or minus 0.05%.
In table l, polypeptide markers are listed which are preferred for the
discrimination
between healthy individuals and individuals suffering from a renal disease,
particularly
from a glomerulonephritis or glomerulopathy.
In table 2, polypeptide markers are listed, which are preferred for a
discrimination between
FSGS and the healthy condition.
io
In table 3, polypeptide markers are listed, which can be used for differential
diagnosis
between FSGS and MCD.
In table 4, polypeptide markers are listed, which are preferred for a
differential diagnosis of
FSGS and MGN.
In table 5, polypeptide markers are listed, which are preferred for a
differential diagnosis
between FSGS on the one hand, and MCD or MGN on the other hand.
In table 6, polypeptide markers are listed, which are preferred for diagnosis
of MCD as
compared to the healthy condition.
In table 7, polypeptide markers are listed, which are preferred for
differential diagnosis
between MCD and MGN.
In table 8, polypeptide markers are listed, which are preferred for
differential diagnosis
between MCD on the one hand, and FSGS or MGN on the other hand.
In table 9, polypeptide markers are listed, which are preferred for diagnosis
of MGN as
3o compared to the healthy condition.
In table 10, polypeptide markers are listed, which are preferred for
differential diagnosis
between MGN on the one hand, and FSGS or MCD on the other hand.
In table 1l, polypeptide markers are listed, which are preferred for diagnosis
of IgA-
nephropathy or MGN on the one hand as compared to the healthy condition.


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In table 12, polypeptide markers are listed, which are preferred for diagnosis
of IgA-
nephropathy as compared to the healthy condition.
In table 13, polypeptide markers are listed, which are preferred for
differential diagnosis
between IgA-nephropathy and MGN.
In table 14, polypeptides are fisted with their respective frequency in
healthy, FSGS, MCD,
and MGN patients.
1o In table 1 S, polypeptides are listed which have been used for differential
diagnosis between
healthy individuals and renal patients using support vector machines according
to Example
1.
In table 16, polypeptides are listed which have been used for differential
diagnosis between
healthy, FSGS, MCD, and MGN patients using random forest analysis according to
Example 1.
In table 17, polypeptides are listed which have been used for differential
diagnosis between
MCD and MGN patients using using support vector machines according to Example
1:
In table 18, polypeptides are listed which have been used for differential
diagnosis between
MCD and FSGS patients using using support vector machines according to Example
I .
In table I9, polypeptides are listed which have been used for differential
diagnosis between
MGN and FSGS patients using using support vector machines according to Example
1.
In table 20 and 21, polypeptides are listed which have been identified in von
Neuhoff et al.
(2004), which has been cited above. .
3o In table 22, polypeptides are listed which can be used for diagnosis of
diabetes and/or
diabetic nephropathy.
In table 23, polypeptides are listed, which are preferred as internal
standards to standardize
the CE-time.


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In table 24, polypeptides are listed, which are preferred as internal
standards to standardize
the CE-time if the pressure method (0.3 to 1 psi) according to Example 1 is
used. These
standards are e.g. preferred as internal standards in diagnosis of IgA-
nephropathy.
In table 2S, clinical data of renal patients are listed whose samples were
used for
identification of polypeptide markers according to Example 1. Abbreviations:
CsA, .
Cyclosporin A; PS , prednisolone; +, frequent relapse; -, currently no
immunosuppression;
~, clinically unclear whether MCD or FSGS.
to The polypeptide maxkers used according to the present invention can be
identified and
their presence can be measured in urine samples. Urine samples can be taken as
known in
the state of the art. Preferably, midstream urine is used in the context of
the present
invention.
The polypeptide markers used according to the present invention can be gene
expression
products such as proteins, peptides, and fragments or other degradation
products . of
proteins or peptides. They carp be modified by posttranslational
modifications, e.g. by
glycosylation, phoshorylation, alkylation or disulfide bond. It is known that
fragments and
degradation products can have a different diagnostic value and/or
physiological role than
2o the protein or peptide they have been derived from. For example, in
different diseases,
different proteolytic degradation products or fragments can be found. It is
also considered
to be within the scope of the present invention if the urine sample is
pretreated to
chemically modify the polypeptide markers contained in the urine and to
measure these
chemically modified polypeptide markers. The polypeptide markers according to
the
present invention have a molecular mass between 400 and 20 000 Da,
particularly between
700 and 14000 Da, more particularly between 800 and 11000 Da.
Preferred polypeptide markers according to the present invention are listed in
tables 1 to .
22, particularly in tables 1 to 21, more particularly in tables 1 to 13.
3o Preferred polypeptides for use as internal standards are listed in tables
23 to 24.
Preferred are also polypeptide markers which are listed in table 1, but not in
table 14
and/or 15 and/or 16 and/or 17 andlor 18 and/or 19 and/or 20 andlor 21 and/or
22.
Preferred are also polypeptide markers which axe listed in table 2, but not in
table 14
and/or 15 andlor 16 and/or 18.
Preferred are also polypeptide markers which are listed in table 3, but not in
table 14
and/or 16 and/or 18.


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Preferred are also polypeptide markers which are listed in table 4, but not in
table 14
and/or 16 and/or 19.
Preferred are also polypeptide markers which are listed in table 5, but not in
table 14
and/or 16 and/or 18 and/or 19.
Preferred . are also polypeptide markers which are listed in table 6, but not
in table 14
and/or 16.
Preferred are also polypeptide markers which are listed in table 7, but not in
table 14
and/or 16 and/or 17.
Preferred are also polypeptide markers which are listed in table 8, but not in
table 14
l o and/or 16.
Preferred are also polypeptide markers which are Listed in table 9, but not in
table 14
and/or 16 and/or 20 andlor 2I .
Preferred are also polypeptide markers which are listed in table 10, but not
in table 14
and/or 16.
Preferred are also polypeptide markers which are listed in table 11, but not
in table 14
andlor 16.
Renal disease according to the present invention relates to any kind of renal
disease or
kidney dysfunction known to the person skilled in the art, for example IgA-
nephropathy,
2o MGN (membranous glomerulonephritis), MCD (minimal-change disease), FSGS
(focal-
segmental glomerulosclerosis), or diabetic nephropathy. Particularly, renal
disease relates
to a glomerulopathy such as IgA-nephropathy, MGN, MCD, or FSGS. Even more
particularly renal disease relates to IgA-nephropathy, MCD, or FSGS. Most
particularly,
renal disease relates tn IgA-nephropathy
The glomerulopathies are a subgroup of renal diseases. Glomerulopathies
comprise a
several diseases of different etiology. Glomerulopathies are characterized by
pathomorphological changes in rnalpighian corpuscles, glomerulus, and Bowman's
_
capsule. As a consequence of these changes, further pathomorphological changes
may
3o appear in other parts of the nephron and interstice.
IgA-nephropathy is also known as Berger-Nephritis. IgA-nephropathy is the most
common
glomerulopathy. It may be a specif c, kidney-limited, form of purpura
Schoenlein-Henoch
(also known as anaphylactoid purpura) with increased plasma concentration of
IgA. The
3s histopathology includes all forms of glomerular lesions and deposits of IgA
in the
mesangium. Clinically, IgA nephropathy presents as micro- and macro-
hematouria.
Therapy may be attempted with ACE inhibitors and omega-3 fatty acids.
Progression of


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the disease occurs over the course of several years and includes transition
into progressive
renal insufficiency.
MGN is characterized by thickening of the basal membrane and granular
subepithelial IgG
s deposits. MGN becomes frequently manifest in the between the age of 40 and
50. It is
frequently caused by medicaments, e.g. gold, D-penicillamine, or ACE
inhibitors. Therapy
of MGN may be attempted with glucocorticoids or cyclophosphamide. MGN is a
nephrotic
syndrome, a transition into progressive renal insufficiency may take several
years.
1o MCD is also known as lipoid nephrosis. MCD is the most common cause of a
nephrotic
syndrome in children. The etiology of the disease is unknown. Histologically,
no or only
very discrete changes can be found. Therapy of MCD may include treatment with
glucocorticoids, , cyclosporin A, or cyclophosphamide. In children, the
disease
spontaneously heals in 90% of the cases, in adults in 50% of the cases. A
transition into
15 FSGS is possible.
FSGS is also known as IgM-nephropathy. FSGS is typically characterized by
deposits of
IgM and C3 in the mesangium. Clinically, it becomes manifest as a nephrotic
syndrome.
Therapy of FSGS may include treatment with glucocorticoids, cyclosporin A; or
2o cyclophosphamide._ Prognosis is poor and includes transition into
progressive renal
insufficiency.
Diabetic nephropathy is also known as diabetic glomerulosclerosis. Diabetic
nephropathy
is the most common cause for requirement of dialysis treatment.
In summary, it is evident that renal diseases include a variety of diseases
which may show
quite similar histology. However, etiology, treatment, and prognosis can be
quite different
for each disease. For example, IgA-nephropathy requires different treatment
from any
other glomerulopathy described above: In IgA-nephropathy, treatment with ACE
inhibitors
3o may be attempted, which would not be recommendable in the case of MGN.
Therefore,
fast and reliable diagnosis is of great importance for treatment.
In the context of the present invention, diagnosing or diagnosis means that,
for an
individual patient, the probability of having the.respective disease is
determined.
Diagnosis may also include confirming a preliminary diagnosis, particularly a
preliminary
diagnosis established by a different method.


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Furthermore, in a preferred embodiment, diagnosis according to the present
invention
particularly relates to "differential diagnosis". The term "differential
diagnosis" relates to
distinguishing between two different diseases, i.e. to determining for an
individual patient
the probability of having a certain first disease as compared to having a
certain second
disease. More particularly, differential diagnosis according to the present
invention relates
to distinguishing between at least two renal diseases chosen from the group
consisting of
IgA-nephropathy, MGN, MCD, FSGS, and diabetic nephropathy.
In another embodiment; the present invention relates to a method for the
differential
diagnosis of a renal disease, the method comprising:
a) measuring the presence or the absence of a polypeptide marker in a urine
sample, wherein the polypeptide marker is selected from the group of
polypeptide markers shown in table 1 to 22, and
b) comparing the probability of the presence of this marker in a disease
patient to
the probability of the presence of this marker in a control patient, wherein
2o cl) if the probability of the presence of this marker in a disease patient
is higher than
the probability of the presence of this marker in a contral patient, the
presence of
this marker is indicative for a higher probability of having the disease
rather than
the control condition, or
c2) if the probability of tlae presence of this marker in a disease patient is
lower than
the probability of the presence of this marker in a control patient, the
absence of
the marker is indicative for a higher probability of having the disease rather
than
the control condition.
3o Preferably, the individual probabilities according to step b) are as
indicated in the tables.
The term '°measuring" according to the present invention relates to
determining the
presence of a polypeptide or other substance of interest.
The decision whether a polypeptide marker is present or absent may depend on
definition
of a suitable threshold value. The threshold value can either be defined
through the
sensitivity of the method of measurement, or it can be defined at will. The
threshold in the


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context of the present invention is 25 finol/~.l in a sample which has been
injected into a
mass spectrometer according to Example 1. However, this threshold may be the
same
when other methods are used. This threshold coincides with the detection
threshold of a
typical mass spectrometer. This threshold corresponds approximately to a
concentration of
the polypeptide marker in the urine sample of 50-5000 pmol/l. If different
thresholds are to
be used (e.g. when using another detection method), the corresponding
probabilities may
differ, but can easily be established by the person skilled in the art.
The "disease patient" according to the present invention is suffering from a
renal disease.
to Particularly, the disease is at least one from the group consisting of IgA-
nephropathy,
MGN, MCD, FSGS, and diabetic nephropathy.
The "control patient" can either be healthy or suffering from a disease
different from the
one the disease patient is suffering from, i.e. the control patient can either
represent the
healthy condition or a disease or group of diseases. Particularly, the
represented disease is
at least one from the group consisting of IgA-nephropathy, MGN, MCD, FSGS, and
diabetic nephropathy.
Tables 1 to 14, 16, 20, 21, and 22 list the probability (also designated as
"frequency") of a
2o given polypeptide marker being present in a urine sample of a healthy
control patient or a
control patient suffering from a certain disease. The discrimination factor
indicates the
difference between the probability of presence in the disease as compared to a
given
control condition. The discrimination factor can easily be calculated from the
respective
probabilities. The higher the discrimination factor, the better is the
potential of the given
marker to distinguish between the disease and the control condition. An
absolute value of
the discrimination factor of 0.40 or higher is preferred.
The person skilled in the art is able to establish similar tables for the
polypeptide. markers
by himself and/or to refine the data contained in the tables, e.g. based on
further patient
3o data and/or according to different thresholds for the presence of the
polypeptide marker.
For diagnosis, the probability of the presence of the polypeptide marker in a
disease patient
is compared to the probability of the presence of this marker in a control
patient, wherein
the individual probabilities are as indicated in the tables. If the
probability of the presence
of this marker in a clisease patient is higher than the probability of the
presence of this
marker in a control patient, then the presence of this marker in the sample is
indicative that
the patient from whom the sample originates has a higher probability of having
the disease


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rather than the control condition. If the probability of the presence of this
marker in a
disease patient is lower than the probability of the presence of this marker
in a control
patient, then the absence of this marker in the sample is indicative that the
patient from
whom the sample originates has a higher probability of having the disease
rather than the
control condition.
For example, a given marker may have a probability of 73% of being present in
a control
representing IgA-nephropathy but a probability of 0% of being present in a
control
representing the healthy condition. If this marker is present in the sample,
then the
individual is diagnosed as having a 73% probability of suffering from IgA-
nephropathy as
compared to being healthy. If this marker is not present in the sample, then
the individual
is diagnosed as having a 73% probability of being healthy instead of suffering
from IgA-
nephropathy.
is Thus, diagnosis can be established according to statistical methods
familiar to the 'person
skilled in the art.
The invention can be carried out using only one of the polypeptide markers or
using a
plurality of the polypeptide markers. Preferably, presence of a plurality of
polypeptide
2o markers is measured. Preferably at least 3 of the markers, more preferably
at least 10 of the
markers, even more preferably at least 20, most preferred at least 50 of the
markers
according to the present invention are measured.
An advantage of the present invention is that it provides a multitude of
suitable markers.
25 Measuring a plurality of marker can increase both sensitivity and
selectivity of diagnosis.
Therefore, also markers which show low discrimination factors between the
disease and
control can be used for diagnosis if they are combined with other markers.
If a plurality of polypeptide markers is used, a "pattern" is be generated
which contains the
3o information about the presence for each marker measured. This pattern can
then be
compared to the pattern of probabilities of presence of the polypeptide
markers in a disease
or control patient. Each table represents a pattern of probabilities of
finding given
polypeptide markers in certain disease and control patients.
35 Therefore, in a preferred embodiment, the present invention relates to a
method for the
differential diagnosis of a renal disease, the method comprising:


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a) establishing a pattern of presence or absence for a plurality of
palypeptide
markers in a urine sample, wherein at least one polypeptide marker is selected
from the group of polypeptide markers shown in table 1 to 22, and
b) comparing the probability of finding this pattern in a disease patient to
the
probability of finding this pattern in a control patient, wherein
cl) if the probability of finding the pattern in a disease patient is higher
than the
probability of the finding the pattern in a control patient, finding this
pattern is
indicative for a higher probability of having the disease rather than the
control
condition, or
c2) if the prabability of finding the pattern in a disease patient is lower
than the
probability of the finding the pattern in a control patient, finding this
pattern is
indicative for a lower probability of having the disease rather than the
control
condition, or -
Preferably, the individual probability for the at least one polypeptide marker
according to
step b) is as indicated in the tables.
Comparison of the found pattern with the probability of finding the pattern in
a disease or
control patient can be performed according to statistical mefhods known in the
art.
Preferably, automated methods are employed, e.g. CART-analysis, random forest
analysis,
and support vector machines (SVM, see e.g. Xiong. M., et al. (2001). Biomarker
identification by feature wrappers. CJenome Research vol. 11, p. 1878-1887).
Comparison
can also be performed simultaneously for several different patterns and the
probability of
finding them.
Thus, the measured pattern is typically compared to the probability of finding
the pattern in
at least two different conditions. An example for diagnosis and differential
diagnosis of
renal diseases according to this method is shown in Fig. 3.
If necessary, the urine samples may be pre-treated before measurement of the
palypeptide
marker. Particularly, lipids, nucleic acids or polypeptides may be purified
from the sample
according to methods known in the art, including filtration, centrifugation,
or extraction
methods such as chloroform/phenol extraction.


CA 02473814 2004-07-13
-13-
Measuring the presence of a polypeptide marker can be done by any method known
in the
art.
Preferred methods include gas phase ion spectrometry, such as laser
desorption/ionization
mass spectrometry, surface enhanced laser desorption/ionization time-of flight
mass
spectrometry (SELDI-TOF MS) and CE-MS. These spectrometry methods allow to
measure the polypeptide markers without the need for ligands such as
antibodies or
aptamers.
to Urine sample generally are highly complex, i.e. they contain numerous
polypeptides. In
case of high complexity, a spectrometric analysis becomes difficult. To reduce
the
complexity of the sample, the polypeptides contained in the sample may be
separated by
any suitable means, e.g. by electrophoretic separation, affinity-based
separation, or
separation based on ion exchange chromatography. Particular examples include
gel
electrophoresis, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE),
capillary
electrophoresis, metal-affinity chromatography, immobilized metal-affinity
chromatography (IMAC), affinity chromatography based on lectins, liquid
chromatography, high pressure liquid chromatography (HPh,C), and reversed-
phase HPLC,
cation exchange chromatography, and selectively binding surfaces (such as the
surfaces
used in SELDI-TOF, see below).
2D-PAGE is commonly used for polypeptide separation aaad can be combined with
mass
spectrometry (MS) yielding identification of individual polypeptides. Over
1000 protein
spots can be discerned with 2D-PAGE. However, each single spot must be
analysed
separately by MS/MS for identification.
SELDI (surface enhanced laser desorption/ionization) time-of flight mass
spectrometry is
currently applied in many fields of biomedical sciences.
3o In the SELDI system, the ProteinChip Arrays are the most important
component. They are
narrow metal strips carrying 8 or 16 spots in a row on the surface. Samples to
be analyzed
are directly applied to the spots, either as a standing drop or in volumes up
to 500 ~1, by
using sample holders called "bioprocessors" as supporting units. They are
placed onto the
arrays during incubation and washing steps and removed again afterwards. The
different
types of arrays belong to two main series: chromatographic arrays, presenting
hydrophobic, hydrophilic, canon-exchanging, anion- exchanging or immobilized
metal ion


CA 02473814 2004-07-13
-14-
affinity-surfaces, and preactivated arrays with chemical groups to allow the
covalent
coupling of proteins. Preferably, a chip with ration-exchange surfaces is
used. As the
ProteinChip Arrays do not only support the sample but specifically interact
with the
biomolecules, the composition of the analyte depends on the array type used
and the
washing conditions applied. This explains why the SELDI-process can be defined
as a
further development of the traditional MALDI (matrix assisted laser desorption
/
ionization)-technique. In the SELDI-process, only on those polypeptides are
measured that
actually bind to the chip surface.
1o After binding of sample proteins, the energy absorbing matrix is applied to
each spot. The
matrix rapidly crystallizes and the analysis can start immediately.
The ProteinChip Arrays are placed into the ProteinChip Reader for analysis.
The reader is
a TOF (time-of flight) mass spectrometer in which the proteins are desorbed
and ionized
with the help of a laser beam. As the crystallized proteins are equally
distributed on the
spot surface, the ionizing laser beam always hits a representative average of
the molecules
in the analyte, allowing quantitative calculations. After ionization, the
proteins are
accelerated by an electric field to fly down the flight tube, before reaching
the detector.
The flight time between the laser striking the array surface and the molecules
reaching the
2o detector at the end of the flight tube enables the system to accurately
determine the mass of
the protein species present in the sample (for more detailed information on
the method see
the following review: Merchant: M and Weinberger SR (2000). Recent
advancements in
surface-enhanced laser desorption / ionization - time of flight mass
spectrometry.
Electrophoresis vol. 212, p. 1164-1177).
However, the most preferred method is CE-MS, in which capillary
electrophoresis (CE) is
coupled to mass spectrometry (.MS). CE-MS has been described in detail
elsewhere (see
e.g. German patent application DE 100 21 737, and Kaiser, T., et al.,
Capillary
Electrophoresis coupled mass spectrometry to establish polypeptide patterns in
dialysis
3o fluids. J Chromatogr A, vol. 1013, p. 157-171(2003)).


CA 02473814 2004-07-13
-15-
CE is known to the person skilled in the art. In brief, the sample is loaded
onto an
electrophoresis capillary and a voltage of up to 50 kV, typically up to 30 kV,
is applied.
Typical capillaries are fused silica capillaries, i.e. glas capillaries
comprising an outer
sheath as mechanical support and to improve mechanical flexibility, e.g. a
sheath made of
thermoplastic material. Typically, the capillary is untreated, i.e. it shows
hydroxy-groups
on its inside. However, the capillary may also be coated on the inside. E.g.,
hydrophobic
coating can be used to improve discriminatory power. In addition to the
voltage, also
pressure may be applied, which is typically in the range of 0 to 1 psi. The
pressure can also
be applied or increased during the run.
to
To improve discriminatory power, also a stacking protocol can be applied when
loading
the sample: Before loading of the sample, a base is loaded, then the sample is
loaded, then
an acid. The principle is to capture the analyte ions between a base and an
acid. If voltage
is applied, the positively charges analyte ions move towards the base. There,
they get
negatively charged and move into the opposite direction towards the acid,
where they get
positively charged. This stacking repeats itself until acid and base are
neutralized. Then,
the separation starts from a well concentrated sample.
The sample is contained in an appropriate buffer in which polypeptides are
soluble, e.g.
2o phosphate buffer. For CE-MS coupling, it is preferred to use volatile
solvents and to work
under mostly salt-free conditions to avoid contamination of the =MS. Examples
comprise
acetonitrile, isopropanol, methanol, and the like. The solvents can also be
combined with
water and a weak acid (e.g. 0.1% formic acid), the latter to protonate the
analyte. The
polypeptides in the sample are separated according to size and charge, which
determine the
run-time in the capillary. CE is characterized by high separating power and
short time of
analysis.
For subsequent MS analysis, either fractions collected from the CE can be
analyzed as
separate batches or, preferably, the CE system can be coupled via a suitable
interface to the
3o mass spectrometer to allow continous flow analysis. Alternatively, the flow
from the CE
may be used to generate continuous "separation tracks", which can be analyzed
separately.


CA 02473814 2004-07-13
-16-
In the mass spectrometer, ions generated from the sample are analyzed
according to the
mass/charge (m/z) quotient. Using mass spectrometry, it is possible to
routinely analyze 10
finol (i.e. 0.1. ng of a 10 kDa polypeptide) with a precision of ~ 0.01%.
Experimentally, it
is possible to analyze even less than 0.1 finol.
Any type of mass spectrometer can be used. In mass spectrometers, an ion-
generating
device is coupled with an suitable analyzer. For example, the electrospray
ionization (ESI)
interfaces are most commonly used to produce ions from liquid samples, whereas
MALDI
is most commonly used to produce ions from individually processed samples.
Different
1o kinds of analyzers are available, e.g. ion trap analyzers or time-of flight
(TOF) analyzers.
Both ESI and MALDI can be combined with essentially all types of mass
spectrometers,
although ESI has usually been combined with ion traps, whereas MALDI has
usually been
combined with TOF.
A preferred CE-MS method according to the present invention includes capillary
electrophoresis coupled online via ESI to a TOF analyzer.
The CE-MS technique permits to measure the presence of several hundred
polypeptide
markers simultaneously in a short time in a small volume with high
sensitivity. Once the
2o presence of the polypeptide markers has been measured, a pattern of the
measured
polypeptide markers is generated and can be compared to a disease pattern by
any of the
methods described further above. However, in many cases it will be sufficient
for
diagnosis to measure only one or a limited number of the markers.
~ The polypeptide sequences can be determined according to methods well-known
to the
person skilled in the art (see e.g. C.S. Spahr et al. (2001). Towards defining
the urinary
proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an
unfractionated tryptic digest. Proteomics vol. l, p. 93-107).
3o Depending on the type of polypeptide marker, it is possible to measure its
presence or
absence by further means. For example, if the polypeptide is biologically
active, its
presence may be determined by cellular or enzymatic assays.

f
CA 02473814 2004-07-13
-17-
Presence of a polypeptide earl also be determined by ose of ligands binding to
the
polypeptide of interest. Binding according to the present invention includes
both covalent
and non-covalent binding.
s A ligand according to the present invention can be any peptide, polypeptide,
nucleic acid,
or other substance binding to the polypeptide of interest. It is well known
that
polypeptides, if obtained or purified from the human or animal body, can be
modified, e.g.
by glycosylation. A suitable ligand according to the present invention may
bind the
polypeptide also via such sites.
1o
Preferred ligands include antibodies; nucleic acids, peptides or polypeptides,
and aptamers,
e.g. nucleic acid or peptide aptamers. For many polypeptides, suitable ligands
are
commercially available. Furthermore, methods to generate suitable ligands are
well-known
in the art. For example, identification and production of suitable antibodies
or aptamers is
15 also offered by commercial suppliers.
The term "antibody" as used herein includes both polyclonal and monoclonal
antibodies,
as well as fragments thereof, such as Fv, Fab and F(ab)2 fragments that are
capable of
binding antigen or hapten.
Preferably, the ligand should bind specifically to the polypeptide to be
measured. "Specific
binding" according to the present invention means that the ligand should not
bind
substantially to ("cross-react" with) another polypeptide or substance present
in the sample
investigated. Preferably, the specifically bound protein or isoform should be
bound with at
least 3 times higher, more preferably at least 10 times higher and even more
preferably at
least 50 times higher affinity than any other relevant polypeptide.
Non-specific binding may be tolerable, particularly if' the investigated
peptide or
polype;ptide can still be distinguished and measured unequivocally, e.g.
according to its
3o size on a Western Blot, or by its relatively higher abundance; in the
sample.
A method for measuring the presence of a polypeptide of interest may comprise
the steps
of (a) contacting a polypeptide with a specifically binding ligand, (b)
(optionally)
removing non-bound ligand, (c) measuring the presence or amount of bound
ligand.


CA 02473814 2004-07-13
- 1g -
Binding of the ligand can be measured by any method known in the art: First,
binding of a
ligand may be measured directly, e.g. by NMR or surface plasmon resonance.
Second, the
ligand also serves as a substrate of an enzymatic activity o~f the peptide or
polypeptide of
interest, an enzymatic reaction product may be measured (e.g. the presence of
a protease
can be measured by measuring the amount of cleaved substrate, e.g. by Western
Blot).
Third, the ligand may be coupled covalently or non-covalently to a label
allowing detection
and measurement of the ligand.
1 o Labeling may be done by direct or indirect methods. Direct labeling
involves coupling of
the label directly (covalently or non-covalently) to the ligand. Indirect
labeling involves
binding (covalently or non-covalently) of a secondary ligand to the first
ligand. The
secondary ligand should specifically bind to the first ligand. Said secondary
ligand may be
coupled with a suitable label and/or be the target (receptor) of tertiary
ligand binding to the
secondary ligand. The use of secondary, tertiary or even higher order ligands
is often used
to increase the signal. Suitable secondary and higher order ligands may
include antibodies,
secondary antibodies, and the well-known streptavidin-biotin system (Vector
Laboratories,
Inc.)
2o The ligand or substrate may also be "tagged" with one or more tags as known
in the art.
Such tags may then be targets for higher order ligands. Suitable tags include
biotin,
digoxygenin, His-Tag, Glutathion-S-Transferase, FLAG, GFP, myc-tag, influenza
A virus
haemagglutinin (HA), maltose binding protein, and the like. In the case of a
peptide or
polypeptide, the tag is preferably at the N-terminus and/or C-terminus.
'
Suitable labels are any labels detectable by an appropriate detection method.
Typical labels
include gold particles, latex heads, acridan ester, luminol, ruthenium,
enzymatically active
labels, radioactive labels, magnetic labels ("e.g. magnetic beads", including
paramagnetic
and superparamagnetic labels), and fluorescent labels.
Enzymatieally active labels include e.g. horseradish peroxidase, alkaline
phosphatase,
beta-Galactosidase, Luciferase, and derivatives thereof. Suitable substrates
for detection


CA 02473814 2004-07-13
° -19-
include di-amino-benzidine (DAB), 3,3'-5,5°-tetramethylbenzidine, NBT-
BCIP (4-vitro
blue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl-phosphate, available
as ready-
made stock solution from Roche Diagnostics), CDP-StarTM (Amersham
Biosciences),
ECFTM (Amersham Biosciences). A suitable enzyme-substrate combination may
result in a
colored reaction product, fluorescence or chemoluminescence, which can be
measured
according to methods known in the art.
Typical' fluorescent labels include fluorescent proteins (such as GFP and its
derivatives),
Cy3, CyS, Texas Red, Fluorescein, the Alexa dyes (e.g. Alexa 568), and quantum
dots.
to
Typical radioactive labels include 355 l2sh 3zP~ 33P~ and the like.
Thus, suitable measurement methods according the present invention also
include
precipitation (particularly immunoprecipitation), electrochemiluminescence
(electro-
generated chemiluminescence), RIA (radioimmunoassay), ELISA (enzyme-linked
immunosorbent assay), sandwich enzyme immune tests, electrochemiluminescence
sandwich immunoassays (ECLL~), dissociation-enhanced lanthanide fluoro immuno
assay
(DELFIA), scintillation proximity assay (SPA), turbidimetry, nephelometry,
latex-
enhanced turbidimetry or nephelometry, or solid phase i~:nmune tests. Further
methods
2o known in the art (such as gel electrophoresis, 2D gel electrophoresis, SDS
polyacrylamide
gel electrophoresis (SDS-PAGE), Western Blotting), can be used alone or in
combination
with labeling or other detection methods as described above.
The ligand may also be present on an array. Said array contains at least one
additional
ligand, which may be directed 'against a peptide, polypeptide or a nucleic
acid of interest.
Said additional ligand may also be directed against a peptide, polypeptide or
a nucleic acid
of no particular interest in the context of the present invention. Preferably,
ligands for at
least five, more preferably at least 10, even more preferably at least 20
polypeptide
markers according to the present invention are contained on the array.
According to the present invention, the term "array" refers to a solid-phase
or gel-like
carrier upon which at least two compounds are attached or bound in one-, two-
or three-


CA 02473814 2004-07-13
-20-
dimensional arrangement. Such arrays (including "gene chips", "protein chips",
antibody
arrays and the like) are generally known to the person skilled in the art and
typically
generated on glass microscope slides, specially coated glass slides such as
polycation-,
nitrocellulose- or biotin-coated slides, cover slips, and membranes such as,
for example,
membranes based on nitrocellulose or nylon.
The array may include a bound ligand or at least two cells expressing each at
least one
ligand.
1o It is also contemplated to use "suspension arrays" as arrays according to
the present
invention (Nolan JP, Sklar LA. (2002). Suspension array technology: evolution
of the flat-
array paradigm. Trends Biotechnol. vol. 20(1), p: 9-12). In such suspension
arrays, the
carrier, e.g. a microbead or microsphere, is present in suspension. The array
consists of
different microbeads or microspheres, possibly labeled, carrying different
ligands.
The invention further relates to a method of producing arrays as defined
above, wherein at
least one ligand is bound to the carrier material in addition to other
ligands.
Methods of producing such arrays, for example based on solid-phase chemistry
and photo-
labile protective groups, are generally known (US 5,744,305). Such arrays can
also be
brought into contact with substances or substance libraries and tested for
interaction, for
example for binding or change of conformation. Therefore, arrays comprising a
polypeptide marker according to the present invention may be used for
identifying ligands
binding specifically to said peptides or polypeptides.
To determine the sequence of .a polypeptide, it should be purified to the
highest level
achievable. However, the polypeptide does not need to be completely isolated.
For
example, it is enough to have the polypeptide detectable as a coomassie-
stained band in a
polyacrylamide gel. The corresponding gel piece can then be cut out and used
for the next
3o identification steps. After purification of the polypeptide, it can be;
enzymatically digested
with trypsin and the molecular weights of the resulting fragments determined
using any
suitable method, for example mass spectrometry. Using mass spectrometry, each
polypeptide displays a characteristic "fingerprint" of fragments allowing its
identification


CA 02473814 2004-07-13
-21 -
by database searches. In case that the polypeptide to be identified is not
present in the
database or if the researcher wants to have a closer characterization for any
reasons, the
polypeptide fragments can also be sequenced according to methods known in the
art.
CE-MS allows particularly easy determination of the polypeptide sequences. The
capillary
electrophoresis elution time for each marker is listed in the tables. Thus, it
is possible to
collect the fraction containing the polypeptide at relatively high purity. If
a single fraction
contains insufficient material, fractions of more than one experiment may be
pooled.
1o Sequences of some of the polypeptide markers are listed as SEQ ID NO: 1 to
5. Their
masses as measured by CE-MS and their respective sequences are as follows:
SEQ mass sequence description


ID NO: [Da]


1 8765,9 FTFHADICTLSEKERQIKKQTALVEL fragment of human


albumin, C-terminus


VKHKPKATKEQLKAVMDDFAAFV amino acids 531-609.


EKCCKADDKETCFAEEGKKLVAAS


QAALGL


2 10046,3 TYVPKEFNAETFTFHADICTLSEKER ft'agment of human


albumin, C-terminus,


QIKKQTALVELVKHKPKATKEQL:KA wino acids 520
to


VMDDFAAFVEKCCKADDKETCFAE 609.


EGKKLVAASQAALGL


3 950.0 GGRPSRPPQ fragment of Salivary


proline-rich protein


4 1292.5 GFRHRHPDEAA fragment of alpha


fibrinogen


5 1448.8 GLITLIGINPSLHT fragment of olfactory


receptor 8B4


Figure legends:
Fig. 1 Depiction of the information from a crude CE-~MS analysis (A) as a
three
dimensional contour plot (left side). Here a contour plot of urine from a
healthy
volunteer is shown, mass per charge on the Y-axis a gainst the retention time
in min
(X-axis), signal intensity colour coded. Next, the signal to noise is
calculated and
2o the noise removed, thus leaving only actual signals (B). The software
calculates the
actual mass (C) based on both isotopic distribution and conjugated masses.
This


CA 02473814 2004-07-13
-22-
results in a table of up to 1500 polypeptides defined via their mass and
retention
time. As an example, bottom right shows 17 polypel9tides found in the sample.
CE-
t, CE-time (migration time) ; int., intensity; m.p.c., mass per charge, cal.
m.,
calculated mass.
Fig. 2 Contour plots of polypeptides (actual masses) for healthy subj ects
(NC) and for
patients with focal-segmental glomerulosclerosis (FSGS), minimal-change
disease
(MCD) and membranous glomerulonephritis (MGT are shown. The upper mass
limit for each plot (i.e. the maximum value along thc; X-axis) is indicated on
the top
to left of each plot. As evident, the contour plots differ significantly
between the
healthy subjects and the 1-enal disease groups.
Fig. 3 Flow sheet for diagnosis and differential diagnosis of renal diseases
(example).
Samp., sample; MS-dat., MS-data; Disea., disease; Y, yes; N, no; n.d., no
disease;
d.n., diabetic nephropathy, FSGS, FSGS; MGN, MGN; MCD, MCD; IgA, IgA-
nephropathy, diff., differential diagnosis
The invention is further illustrated by the following examples:
Example 1
Participants:
After local Ethics Committee approval, informed consent was obtained from all
participants. We examined a group of 57 healthy individuals with normal renal
function in
order to establish normal urinary protein patterns with CE-MS. In addition, we
studied 44
patients with biopsy-proven minimal-change disease (n: _. 16; MCD), membranous
glomerulonephritis (n = 18; MGN), and focal-segmental glomerulosclerosis (n =
10;
FSGS) (Table 1).
CE-MS Analysis:
Spot urine samples were collected from all participants in the morning after
voiding the
first urine. Samples were prepared as described in detail elsewhere (Wittke S,
Fliser D,
Haubitz M, et aI: Determination of peptides and proteins in human urine with
CE-MS -
suitable tool for the establishment of new diagnostic markers. J Chroryccetogr
A 1013:173-


CA 02473814 2004-07-13
-23-
181, 2003). The CE-MS analysis was established as described previously (Kaiser
T,
Hermann A, Kielstein JT, et al: Capillary Electrophoresis coupled mass
spectrometry to
establish polypeptide patterns in dialysis fluids. J Chromatogr A 1013: 157-
171, 2003),
using a Beckman Coulter PACE system coupled to a Mariner TOF mass spectrometer
(ABI). CE capillaries were from Beckman, ID/OD 751360 ~m and 90 cm in length.
The
mobile phase used contained 30% methanol and 0.5% formic acid in water. The
same
liquid was used for the sheath flow, which was applied at 2 ul/min. Sample
injection was
performed with pressure: 1 psi for 20 sec. Under these conditions about 100 nl
of sample
could be injected. For sample stacking, the following protocol was applied:
injection of 1M
l0 NH3 for 7 sec., injection of sample, injection of 2M formic acid for 5 sec.
The subsequent
CE-MS run was performed at +30 kV with the sequence of the following
pressures: 40 min
at 0 psi, 2 min at 0.1 psi, 2 min at 0.2 psi, 2 min at 0.3 psi, 2 min at 0.4
psi, 80 min at 0.5
psi. For diagnosis of IgA-nephropathy, the following pressure sequence was
used: 40 min
at 0.3 psi, 2 min at 0.4 psi, 2 min at 0.6 psi, 2 min at 0.8 psi, 80 min at 1
psi. After each
run, the CE capillary was rinsed for 5 min with 0.1 M NaOH, followed by 5 min
with
water and 5 min with running buffer.
Statistical analysis:
2o For discrimination between healthy subjects and different groups of
patients with renal
diseases we used the method of Random Forests and the corresponding S-Plus
program
version 6/2002 Breiman L: Random Forests.
(http://oz.berkeley.edu/users/bre~man/randomforest2001.pdf). In this
procedure, a series of
PP subsets of fixed size is selected randomly from all candidate PP. For each
subset, a
classification tree as described in the Classification and Regression Tree
(CART) analysis
is generated (Steinberg D, Colla P: CART - Classification and Regression
trees. San
Diego, CA, Salford Systems 1997), resulting in a classification rule. The
forest prediction
is the unweight plurality of class votes of the series of classification
rules. Over-fitting is
not generated due to Iarge numbers of subset selections. The estimated
generalisation error
is unbiased due to the method of "out of bag" (oob) estimation: each tree is
grown on a
bootstrap sample of cases of the learning sample and the validation is
estimated on the
basis of those cases not selected in the bootstrap sample.
Further, discrimination between groups was also performed using support vector
machines.
This tool has the advantage of discriminating data in high dimensional
parameter space. Its
fast and stable algorithms showed good performance in the evaluation of
clinical markers
(Dieterle F, Muller-Hagedorn S, Liebich HM, Gauglitz G: Urinary nucleosides as
potential

't
CA 02473814 2004-07-13
-24-
tumor markers evaluated by learning vector quantization. Artif Intell.Med
28:265-279,
2003) and different areas of biological analyses like DNA arrays (Brown MP,
Grundy WN,
Lin D, et al: Knowledge-based analysis of microarray gene expression data by
using
support vector machines. Proc hTatl Acad Sci USA 97:262-267, 2000).
Normal urinary polypeptide pattern analysed with CE-MS:
A graphical depiction (contour plot) of a typical sample is presented in Fig.
1 (raw data).1n
one individual sample, between 900 and 2500 PP with molecular weights from 800
up to
l0 30.000 Dalton were detected. Under the conditions used for CE polypeptides
with higher
molecular weights tend to precipitate. Thus larger proteins in general cannot
be detected,
although some (e.g. albumin) can be visualised. A list of polypeptides present
with high
probability that were chosen as internal standards to assure sample
comparability is shown
in table 23. For analysis of protein-rich samples, such as samples from
suspected IgA-
nephropathy patients, higher pressure was applied and the polypeptides
according to table
24 were preferred as internal standards. Repeated analyses of identical
samples did not
reveal any significant differences under identical conditions of the CE-MS run
for an
individual sample.
2o The subsequent electronic data manipulation for one example is summarised
in Fig. 1.
Each run results in the crude spectrum depicted in the upper part of Fig. 1
and is composed
of single spectra (blow up Fig. I) generated every 3 seconds. CE-MS peaks were
identified
in the first data analysis run (Fig. lA). Next, the charge of each peak was
ascertained
utilising both isotopic distribution and conjugated peaks (Fig. 1B). As a
result, conjugated
peaks were summarised in one single peak and the real mass was calculated, as
shown in
Fig. 1 C. Initially, the samples were spiked with external standards of known
mass. This
allowed subsequent definition of internal standards of PP present with high
probability in
the urine samples. Thus the CE-time could be normalized to the internal
standards. By
applying this technique on an average urine sample, roughly 1000 PP can be
detected and
3o described/identified by the two parameters mass and CE-migration time.
The examination of urine obtained from healthy subjects led to the
establishment of peaks
defined by actual mass and CE-time of the PP detected, so-called peak lists,
and contour
plots for each individual. The individual peak lists were deposited in an MS-
Access
database and the probability of each of the PP to appear in a single sample
was calculated.
One-hundred seventy-three PP were present in over 90% of the control samples
examined.
In addition, 156 PP were present in more than 75% of the samples, while
additional 361 PP


CA 02473814 2004-07-13
-25-
were found in over 50% of samples from the healthy individuals. These 690 PP
were found
in more than 50% of all samples obtained from healthy subjects and were used
to establish
a "normal PP pattern".
Urine from patients with renal diseases analysed with CE-1V~S:
Data from the individual runs of 44 patients were sub-grouped in the three
disease groups
and analysed. The values from these databases, representing typical PP
patterns, were
subsequently compared. Significant homology of the protein patterns present in
urine
to samples from each patient group was found within the groups. Typical
examples of urinary
PP patterns from patients with MCD, FSGS, and MGN acre shown in Fig. 2. Each
disease
presents a typical protein contour plot, revealing more than 500 PP.
Subsequently, the data
from the three groups were compared with those obtained in healthy subjects.
Table 16
shows 124 PP found in the urine of more than 95% of healthy subjects and
reveals the
differences to patients with MCD, FSGS, and MGN.
Statistical analysis for discrimination of healthy individuals and patients
with renal disease
using CE-MS data was applied. A list of 800 PP, present with more than 50%
probability
in either disease group was chosen for Random Forest analysis. The correct
classification
2o rate for the discrimination between healthy subjects and renal patients was
96.5 %, as
shown in the following list:
Class Healthy Renal Classification


subjects error


patients


(n 57) (n=44) [%


classified 2 3
as 5


healthy 56 .


classified
as 42 2
3


patients .


After cross-validation a sensitivity of 81.3% and a specificity of 94.3% could
be obtained.
Discrimination of the disease groups was achieved in the learning sample.
However, most
likely due to the small number of FSGS patients, these could not be
discriminated from
MCD when applying cross-validation. Hence, FSGS and MCD were combined into one
group. For the discrimination between healthy subjects, MCD/FSGS and MGN, four
PP
were selected by CART from the list to build a classification tree with five
terminal nodes
(table 15).The correct classification rate in the learning sample is 94.1%.
After cross-


CA 02473814 2004-07-13
-26-
validation it reduces to 84.3% (93.8% for healthy controls, 71.4% for MCD/FSGS
and
92.9% for MGN).
Alternatively, statistical analysis was performed using support vector
machines on the
same data; table 16 shows PP that were employed in this analysis. Using these
PP, the
correct classification was 98.0% after complete cross-validation. Table 17
depicts PP that
were used to discriminate between MCD and MGN. Here the correct classification
was
94.1 % after complete cross-validation. Further, it was possible to separate
patients with
MCD and FSGS and patients with MGN and FSGS with (cross-validated)
classification.
rates of 92.3 % and 89.3%, respectively (tables 18 and 19). These results can
be valued as
a first approach using support vector machines to classify a limited number of
patients.
With increasing patients data the classification will further improve and
become more
stable. The results also indicate that for stable classification the number of
applicable;
variables (polypeptides) depends on the number of cases (patients), hence an
increase in
patients will allow to use even more PP for classification.


CA 02473814 2005-07-13
27
SEQUENCE LISTING
(1) GENERAL INFORMATION:
(i) APPLICANT: MISCHAK, Harald
KAISER, Thorsten
WITTKE, Stephen
WALDEN, Michael
(ii) TITLE OF INVENTION: METHOD AND MARKERS FOR THE DIAGNOSIS OF
RENAL DISEASES
(iii) NUMBER OF SEQUENCES: 5
(iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: GOUDREAU GAGE DUBUC
(B) STREET: 800 PLACE-VICTORIA, P.O.BOX 242,#3400, Stock
Exchange Tower
(C) CITY: Montreal
(D) STATE: Quebec
(E) COUNTRY: Canada
(F) ZIP: H4Z lE9
(v) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Floppy disk
(B) COMPUTER: IBM PC compatible
(C) OPERATING SYSTEM: PC-DOS/MS-DOS
(D) SOFTWARE: PatentIn Release #1.0, Version #1.30
(vi) CURRENT APPLICATION DATA:
(A) APPLICATION NUMBER: CA 2,473,814
(B) FILING DATE: 13-JUL-2004
(C) CLASSIFICATION:
(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: LECLERC, Alain M.
(C) REFERENCE/DOCKET NUMBER: AML/14151.1
(ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: 514-397-7675
(B) TELEFAX: 514-397-4382
(2) INFORMATION FOR SEQ ID N0:1:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 81 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo Sapiens


CA 02473814 2005-07-13
28
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:1:
Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln
1 5 10 15
Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Pro Lys
20 25 30
Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala Ala Phe
35 40 45
Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu
50 55 60
Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly Leu His
65 70 75 80
Met
(2) INFORMATION FOR SEQ ID N0:2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 89 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo Sapiens
(xi)SEQUENCE DESCRIPTION:
SEQ
ID
N0:2:


ThrTyr ValProLys GluPheAsn AlaGluThr PheThrPhe HisAla


1 5 10 15


AspIle CysThrLeu SerGluLys GluArgGln IleLysLys GlnThr


20 25 30


AlaLeu ValGluLeu ValLysHis LysProLys AlaThrLys GluGln


35 40 45


LeuLys AlaValMet AspAspPhe AlaAlaPhe ValGluLys CysCys


50 55 60


LysAla AspAspLys GluThrCys PheAlaGlu GluGlyLys LysLeu


65 70 75 80


ValAla AlaSerGln AlaAlaLeu Gly


85




CA 02473814 2005-07-13
29
(2) INFORMATION FOR SEQ ID N0:3:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 9 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo sapiens
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:3:
Gly Gly Arg Pro Ser Arg Pro Pro Gln
1 5
(2) INFORMATION FOR SEQ ID N0:4:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 11 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo sapiens
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:4:
Gly Phe Arg His Arg His Pro Asp Glu Ala Ala
1 5 10
(2) INFORMATION FOR SEQ ID N0:5:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 14 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(vi) ORIGINAL SOURCE:
(A) ORGANISM: Homo sapiens
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:5:
Gly Leu Ile Thr Leu Ile Gly Ile Asn Pro Ser Leu His Thr
1 5 10


CA 02473814 2004-07-13
-1-
Table 1:
molecular migration discrimination
weight time [min)factor fre uenc


[~a) glomerulo-healthy
nephritis


830,5 25,3 0,42 55 12


836,5 35 0,64 80 16


862,4 48,7 0,45 57 12


866,4 37,9 0,62 77 16


870,4 33,9 0,45 52 7


874,5 29,7 0,46 75 29


876,4 48,9 -0,41 57 98


882,6 36,5 -0,4 55 95


903,4 46,8 -0,42 14 55


909,4 40,3 0,67 70 3


925,4 50,7 0,63 77 14


926,5 36,1 -0,44 32 76


943,5 30 0,52 80 28


946,5 _46,8 -0,44 41 84


950,5 36 0,61 66 5


952,5 32 0,52 64 12


956,4 49,5 -0,54 7 60


978,5 35 0,53 55 2


980,6 34,6 -0,45 43 88


982,5 31,9 0,53 64 10


983,5 35,1 0,41 55 __
14


988,6 49,9 -0,48 9 57


990,6 32 0,42 61 19


991,4 37,7 0,41 55 14


994,5 33,3 0,51 75 24


995,6 36,4 0,46 68 22


1000,5 34 -0,58 36 95


1006,4 35,7 -0,48 30 78


1008,5 34,4 -0,5 43 93


1010,6 30,6 -0,58 25 83


1013,4 39,3 -0,43 9 52


1015,6 38,2 0,47 52 5


1028,6 37,8 -0,55 43 98


1033,6 39,1 0,62 70 9


1038,6 34,4 0,43 57 14


1046,6 38,6 -0,76 20 97


1047,6 30,4 -0,44 41 84


1073,6 34,7 0,59 75 16


1075,6 29 -0,43 20 64


1102,6 32,9 0,4 52 12


1108,6 29,8 0,47 86 40


1110,4 46,9 -0,5 20 71


1121,6 42,3 -0,46 16 62


1122,5 50,2 -0,41 25 66




CA 02473814 2004-07-13
- Z
1135,6 42,7 -0,61 5 66


1138,6 39,3 0,55 73 17


1139,6 32,2 0,52 59 7


1141,6 38 -0,6 7 67


1157,6 28,5 0,5 80 29


1159,6 39 -0,65 16 81


1163,7 38,1 0,47 50 3


1171,6 32,8 0,64 66 2


1182,6 47,2 -0,45 20 66


1191,6 50,5 -0,41 50 91


1191,8 18,3 0,56 66 10


1198,8 29,2 0,44 75 31


1203,7 24,7 -0,52 5 57


1209,6 50,5 -0,42 48 90


1211,6 31,3 0,5 66 16


1212,7 30,6 0,57 66 9


1219,6 37,3 0,57 77 21


1220,6 30,2 0,42 75 33


1223,5 51,6 -0,6 30 90


1224,7 33,6 -0,41 59 100


1225,7 41,3 0,45 50 5


1235,6 41,4 -0,41 59 100


1237,7 41,6 -0,49 18 67


1246,7 30,5 -0,47 18 66


1256,6 53,4 0,41 55 14


1264,7 26,7 0,44 52 9


1268,6 53,7 -0,47 5 52


1269,7 39,8 0,45 64 19


1270,5 52,5 -0,51 5 55


1279,7 38,3 0,48 64 16


1280,6 51,9 -0,53 9 62


1286 30,7 0,41 84 43


1292,5 53 -0,59 27 86


1297,6 38,7 0,45 86 41


1302,7 31,8 0,54 86 33


1303,6 40,7 -0,44 11 55


1311,8 31,5 0,58 77 19


1319,9 34,8 0,4 59 19


1324,2 40,5 0,5 59 9


1325,5 35,2 0,54 80 26


1333,8 38,8 0,65 82 17


1335,7 39,2 0,57 80 22


1338,7 29,6 0,46 57 10


1338,7 47,2 0,8 82 2


1350,7 50,3 -0,48 2 50


1353,7 39,3 -0,44 45 90


1354,8 45,6 0,55 93 38


1371,7 39,9 0,6 64 3


1371,8 19,3 0,63 89 26


1389,8 19,5 0,5 84 34


1390,7 41,1 0,45 64 19


1398,9 30,5 0,59 73 14


1401,8 46,2 -0,53 9 62


1405,9 17,3 0,49 59 10




CA 02473814 2004-07-13
-3-
1408,9 26,8 0,42 52 10


1414,6 38,1 0,62 86 _
24


1415,7 33,3 0,45 50 5
1419,8 39,7 0,48 77 29


1424,9 35,4 -0,46 25 71


1442,8 33,3 0,63 84 21


1444,6 37,8 0,53 82 29


1448,8 30,3 0,42 75 33


1465,9 28,8 0,59 66 7


1472,1 31,2 0,57 70 14


1474,9 16,9 0,65 77 12


1482 30,4 0,57 84 28


1484 30,4 0,58 89 31


1486,5 30,6 0,45 66 21


1498,7 34,9 0,52 66 14


1499,9 30,6 0,56 91 34


1502,8 28,8 0,44 75 31


1502,9 16,8 0,66 68 2


1508,9 16,8 0,48 57 9


1511,7 38,4 0,55 80 24


1518 26,8 0,45 93 48
1520,7 27,9 0,45 64 19


1527,9 34,7 0,43 73 29


1529,7 54,1 -0,48 36 84


1535 28,3 0,61 73 12


1537,9 31,5 0,43 70 28


1540,7 29,8 0,5 66 16


1542,5 27,2 0,4 52 12


1548,3 31,1 0,46 89 43


1556,8 33,7 0,59 89 29


1567 31,9 0,45 86 41


1567,6 53,9 -0,53 2 55


1568,6 34,3 0,41 70 29


1573,8 4_0,4 0,44 89 45


1574,8 33,9 0,41 61 21


1582,9 27,8 0,51 61 10


1588,4 47,9 -0,61 11 72


1596,9 34 0,64 86 22


1604,3 21,6 0,5 64 14


1604,7 38,1 0,42 73 31


1605,7 __53,3 -0,4 34 74


1611,7 53,2 -0,48 36 84


1612,8 36,8 0,58 91 33


1622 19,2 0,51 91 40


1633,8 24,6 0,42 75 33


1644 18,8 0,46 55 9


1652,3 28,6 0,44 84 40


1669,9 33,4 0,54 75 21


1676 25,3 0,52 _ 12
64


1681,6 40 0,51 82 31


1686,8 38,2 0,67 91 24


1690,8 25,5 0,44 75 31


1692,5 44,2 -0,41 39 79


1699,1 41,9 0,62 86 24




CA 02473814 2004-07-13
-4-
1711 43,3 -0,45 20 66


1718,5 22,6 0,57 66 9


1726 36,3 0,62 70 9


1729,2 26 0,57 70 14


1732 51,6 -0,41 36 78


1739,8 35,7 0,45 86 41


1746,2 46,2 -0,59 25 84
1747,7 50,8 -0,52 5 57


1752,9 39,9 0,46 68 22


1763 24,4 0,57 80 22


1770,4 45,4 0,4 89 48


1777,6 28,6 0,53 70 17


1793,6 28,3 0,49 55 5


1804,7 34 0,45 100 55


1808,1 45,6 0,49 55 _ 5


1810,1 31,8 0,45 64 19


1811,3 31,3 0,55 93 38


1813,4 54,7 -0,47 7 53


1815,2 27,7 0,5 66 16


1819,9 24,1 0,5 64 14


1820,1 31,8 0,48 91 43


1821,2 18,2 0,52 57 5


1822,9 40,7 -0,6 23 83


1824,3 37 -0,52 27 79


1826,1 21,8 0,45 59 14


1831,9 41,5 0,5 59 9


1847,8 57 -0,66 27 93


1851,2 31,6 0,48 86 38


1853 31,2 0,59 82 22


1853,6 46,7 0,47 50 3


1854,2 28,8 0,45 52 7


1856,8 56,3 -0,51 18 69


1857,1 39 0,46 75 29


1864,6 28,6 0,65 82 17


1867 31,8 0,6 91 31


188_3 29,1 -0,49 32 81


1885,7 57,5 -0,4 55 95


1889,2 30,1 0,41 55 14


1889,8 46,4 -0,58 39 97


1891,6 32,3 0,55 77 22


1894,9 22 0,67 86 19


1896,8 53,3 -0,44 11 55


1898,7 26,5 0,45 59 14


1904 27,5 0,48 50 2


1913,4 30,1 0,44 55 10


1916,8 44,7 -0,52 14 66


1920,7 30,6 0,46 91 45


1933,9 32,8 -0,55 36 91


1934,2 16,1 0,71 73 2


1936,5 46,6 -0,42 25 67


1936,7 32,8 0,5 80 29


1944,2 47 -0,68 18 86


1951,1 53 -0,48 16 64


1966,3 25,1 0,71 82 10




CA 02473814 2004-07-13
1973,7 57,1 -0,5 9 59
1977,4 42,9 -0,47 41 88
1982,9 32,2 0,58 82 24
1989,3 43,7 0,69 84 16
1990,8 47,3 -0,71 11 83
2011,5 42 0,41 70 29
2022,6 34,6 0,46 68 22
2025 24,2 0,41 50 9


2028,4 29,9 0,55 80 24
2030,4 31,7 -0,49 32 81
2030,8 46,5 -0,61 25 86


2033,5 27,5 0,46 55


2042 26,4 0,47 95 48


2042,5 40,7 0,5 70 21


2045,9 25,3 0,43 84 41


2047 45,4 -0,46 52 98


2050,8 38,2 0,47 82 34


2065,3 20,9 0,49 52 3


2092 26,7 0,52 66 14


2092,5 41,3 0,59 75 16


2099,2 36,9 0,58 84 26


2103,6 26,7 0,46 89 43


2105,4 32,5 0,52 66 14


2109,3 27,9 0,47 68 21


2117,1 57,1 -0,57 20 78
2127,2 39,6 0,46 75 29


2129,5 35,1 -0,58 39 97


2140,1 26,8 0,52 64 12


2144,3 22 0,47 75 28


2146,3 25,8 0,74 77 3


2147,2 38,4 0,43 64 21


2152,7 29,5 0,51 70 19


2157,2 24,4 0,41 50 9


2174,4 24,6 0,46 68 22


2178,5 21,4 0,48 57 9


2182,5 27,6 0,55 80 24


2207,2 41,9 0,41 61 21


2210,7 25,7 0,64 86 22


2217,7 41,9 0,5 84 34


2221,1 40,7 -0,5 14 64


2223,5 22,6 0,6 68 9


2228,1 25,9 0,51 91 40


2233 31,1 -0,4 55 95


2241,1 22,7 0,49 80 31


2290,7 36,2 0,47 52 5


2291,1 21,9 0,45 50 5


2308,9 26,2 0,41 61 21


2312,5 22,9 0,45 57 12


2322,5 47,1 0,47 52 5


2356,3 24 0,41 57 16


2364,4 38,9 0,49 73 24


2370,7 27,3 0,4 52 12


2391,2 24,3 0,58 70 12I


2406,4 31,8 0,43 84 41




CA 02473814 2004-07-13
-6-
2409,1 41,9 0,43 84 41
2421 28,7 0,41 70 29
2423,1 27,4 0,41 68 28


2426,5 38,5 0,58 89 31


2427,4 24 0,53 84 31


2432,2 38,3 0,66 80 14


2464 47,2 -0,55 7 62


2465 22,8 0,7 75 5
2473,4 41,9 0,44 52 _ 9


2490,7 26,7 0,43 70 28


2493,6 24,6 0,63 77 14


2522,9 24,4 0,47 68 21


2529,2 41,4 -0,47 14 60


2535 37,7 0,42 82 40


2540,5 25,5 0,65 75 10


2548,2 35,1 -0,46 36 83


2566,4 22,2 0,5 57 7


256_8,9 26,9 0,41 70 29


2573,7 16,3 0,57 66 9


2584 43,8 -0,56 41 97


2593,4 25 0,41 57 16


__2614,1 22,5 0,42 59 17-


2619,7 22,9 0,47 50 3


2621,4 25,8 0,56 68 _
12


2644,1 32,5 -0,48 45 93


2660,8 27,1 0,4 59 19


2665,3 39,4 0,46 57 10


2677,6 23,6 0,58 68 10


2698,4 32,1 -0,47 _ 79
32


2713,2 41,3 -0,51 11 62


2719,9 20,2 0,49 55 5


2752,8 25,3 0,56 82 26


2780,4 28,3 0,52 66 14


2790,3 26,8 0,46 61 16


2793,7 36,3 0,64 80 16


2809,1 37,2 -0,48 30 78


2812,5 32,8 0,46 61 16


2830,9 33;2 0,49 68 19


2937,1 26,6 0,46 55 9


2973,7 34,9 -0,58 30 88


2978 26,3 -0,49 34 83


2990,4 33,6 -0,47 20 67


3007,5 30,5 -0,45 23 67


3017,7 46,8 -0,42 18 60


3057,1 56,4 -0,41 43 84


3058,8 35,5 -0,41 45 86


3121,4 42,5 -0,43 57 100


3137 37 -0,42 41 83


3139,4 43,7 -0,53 25 ___
78


3152,6 38,2 -0,45 55 100


3177,4 22,3 -0,45 27 72


3187,7 48,6 -0,4 41 81


3209,2 34,3 -0,47 50 97


3219,5 20,2 0,48 61 14




CA 02473814 2004-07-13
3255,8 42,9 -0,48 36 84


3262 31,5 -0,52 34 86
~


3281 36,8 -0,66 32 98
3282 49,4 -0,4 55 95


3290,9 36,9 -0,57 36 93


3295,8 38,4 -0,55 43 98


3303,2 38,6 -0,57 27 84


3308,6 21,3 0,53 57 3


3309,7 43,6 -0,41 32 72
3319,3 46,2 -0,45 50 95


3333,4 23,3 -0,56 32 88


3334,6 41,7 -0,54 32 86


3337,4 36,2 -0,45 43 88


3343,8 43,8 -0,46 45 91


3405,7 37,8 -0,6 39 98


3422,5 38,7 -0,58 32 90


3436 26,4 -0,5 20 71


3479,3 48,5 -0,5 50 100


3503,3 23,2 -0,43 16 59


3530,9 36,8 -0,54 27 81


3583,3 25,2 -0,67 23 90


3589,5 39,1 -0,65 25 90


3617,4 44,8 -0,4 18 59


3631,2 33,1 -0,55 16 71


3634,9 42,6 -0,41 39 79


3682,4 42,8 -0,47 27 74


3686,1 32,6 -0,71 11 83


3697,4 38,8 -0,42 11 53


3701,8 43,4 -0,63 9 72


3707 31,9 -0,69 7 76


371_9,6 44,7 -0,42 41 83


3723_,3 32,5 -0,65 32 97


3735,8 43,9 -0,5 30 79


3760,8 25,9 -0,51 18 69


3802,7 46,2 -0,43 14 57


3816,7 32,2 -0,52 14 66


3852,2 36,9 -0,45 36 81


3871,7 42,9 -0,41 23 64


3946,9 33,1 -0,54 39 93


3969,6 31,3 -0,52 34 86


3987 30,5 -0,42 55 97


4026,2 30,5 -0,42 11 53


4044,7 31,2 -0,57 30 86


4055,2 24,1 0,41 57 16


4154,2 23,7 0,63 77 14


4170,6 46,1 -0,45 7 52


4183,7 26,6 0,42 52 10


4241,2 24,4 0,75 89 14


4283,1 24,3 0,55 64 9


4290,8 41,1 -0,45 43 _
88


4654,8 38,8 -0,4 11 52


4713,7 26,9 0,63 68 5


4748,5 25,4 -0,56 39 95


4772,1 28,9 -0,43 9T 52




CA 02473814 2004-07-13
_ 8 -
4801,2 37,5 -0,49 39 88


4827,1 27,3 051 52 .-_ 2


4863,7 39,2 -0,53 18 71


5213,8 36,8 -0,43 7 50


5229,1 39,9 -0,43 9 52


5575,8 35,7 -0,48 14 62


6171,5 39,6 -0,5 43 93


6212,4 30,6 -0,5 9 59


6400,9 23,4 0,51 52 2


7409,9 26,2 0,49 61 12


7556,6 26,2 0,59 75 16


7572,8 25,7 0,42 55 12


8054,8 16,7 0,63 82 19


8341,2 16,6 0,59 66 7


8653,1 17,2 0,4 52 12


8765,9 17,6 0,56 89 33


9060,7 23 0,46 57 10


9076 23 0,58 68 10


9182 17,1 0,55 64 9


9223,1 22,8 0,64 70 7


9335,5 17,5 0,47 50 3


9868,8 29,5 -0,57 20 78


9933,5 18,4 0,47 50 3


10046,3 18,1 0,7 89 19


10390,1 20,2 0, 58 70 12


10518,8 20,9 0,56 75 19


Table 2:
molecular migration discriminationfreouencv
f%1


weiaht fDa1time ~min1 factor FSGS healthy


803.4 35 2 0,44 60 16


807.3 35 4 0,41 50 9


809.3 25.2 0,5 50 0
817.2 25.6 0.47 50 3
830.5 25,3 0.68 80 12


836.5 35 0,54 70 16


866.4 37.9 0,64 80 16


870.4 33.9 0.43 50 7


874,4 49.~T 0,57 60 3


907.4 27,5 0.57 60 3


909.4 40,3 0,57 60 3


915,4 35 0.48 50 2


925,4 50.7 0,56 70 14


926.5 36,1 -0.46 30 76


939.6 33,1 0,61 70 9


943.5 30 0.42 70 28


946.5 46,8 -0,54 30 84


950,5 36 0.75 80 5


952.5 32 0.58 70 12
953.6 34,5 -0,52 20 72


956,4 49.5 -0,5 10 60




CA 02473814 2004-07-13
_ 9 ..
974,5 27,6 0,41 60 19


978,5 35 0,48 50 2


980.6 34,6 -0.58 30 88


981,6 37,4 -0,47 50 97


982.5 31,9 0.7 80 10


988,6 49.9 -0.47 10 57


990.6 32 0,41 60 19


994,5 33.3 0.46 70 24


995.6 36.4 0.48 70 22


1000,5 34 -0.55 40 95


1002.6 38,5 0.53 60 7


1005,5 35 0,54 70 16


1006.4 35.7 -0,58 20 78


1008.5 34.4 -0.63 30 93


1010.6 30.6 -0.53 30 83


1010,6 50.8 -0.64 0 64


1013,4 39,3 -0.52 0 52


1015,6 38,2 0.55 60 5


1021,5 32,1 0,45 50 5


1028.6 37,8 -0.58 40 98


1033.6 39.1 0.71 80 9


1041.5 51,6 -0.4 20 60


1046.6 38.6 -0.77 20 97


1049.5 39,9 0,45 50 5


1055.6 36.4 0.51 60 9


1071,5 38.7 0.48 50 2


1073,6 34.7 0,64 80 16


1075.6 29 -0,44 20 64


1090,5 36,2 0.42 70 _ 28


1106.6 19.6 0,41 50 9


1108,6 29,8 0,4 80 40


1110.4 46,9 -0.41 30 71


1121.6 42.3 -0.62 0 62


1126.5 42,7 0,51 60 9


1135,6 42,7 -0,66 0 66


1138,6 39.3 0.63 80 17


1139,6 32.2 0,53 60 7


1141.6 38 -0.57 10 67


1157,6 28.5 0,51 80 29


1157.6 16.9 0,5 50 0


1159,6 39 -0,61 20 81


1164.6 38.7 0,46 60 14


1171.6 32,8 0,48 50 2


1182,6 47.2 -0,66 0 66


1186.6 32 0,47 80 33


1191,6 50,5 -0,71 20 91


1191.8 18.3 0.5 60 10


1192.6 40,9 0.46 70 24


1203.7 24.7 -0.47 10 57


1209.6 __ -0,5 40 90
50,5


1211.6 31,3 0.64 80 16


1212,7 30.6 0.61 70 9


1219.6 37.3 0.59 80 21





CA 02473814 2004-07-13
-10-
1224,7 33,6 -0.5 50 100


1225,7 41,3 0,55 60 5


1235.6 41,4 -0,4 60 100


1236,7 34,8 0.44 70 26


1237,7 41,6 -0,47 20 67


1246,7 30,5 -0,46 20 66


1258,7 20,9 0.5 60 10


1263,7 38.6 0.65 70 5


1268,6 53,7 -0,52 0 52


1269,7 39.8 0.51 70 19


1270,5 52,5 -0.55 0 55


1270,6 25,7 0,55 60 5


1274,6 38 0.56 70 14
1279.7 38,3 0.44 60 16


1280.6 51,9 -0.52 10 62


1288,6 46.1 -0,44 40 84


1292.5 53 -0,66 20 86


1294,6 54.4 0.56 70 14


1302,7 31,8 0,57 90 33


1303,6 40.7 -0.45 10 _ 55


1304,8 24.6 0,5 50 0


1305,9 33.4 0.6 70 10


1308,6 53.6 -0,54 30 84


1309,8 38,9 0,41 50 9


1310,7 52,5 0,5 50 0


1311,8 31,5 0,51 70 19


1325,5 35,2 0,44 70 26


1333,8 38.8 0.63 80 17


1335,7 39,2 0,68 90 22


1338,7 47,2 0,78 80 2
1338,7 29.6 0,7 80 10
1350,7 50.3 -0,5 0 50


1353.7 39,3 -0,5 40 90


1354.8 45.6 0,52 90 38


1367,7 26,2 0,41 50 9


1371,7 39.9 0,67 70 3
1371,8 19.3 0.64 90 ~ 26
1377.7 25,4 0.67 70 3


1383.7 52.7 -0,53 0 53


1386 24.4 0,41 50 9


1389.8 19,5 0,56 90 34


1390,7 41,1 0.71 90 19


1394.3 48,1 0,48 60 12


1398,9 30.5 0,56 70 14


1401,8 46.2 -0,62 0 62


1403.8 34,4 0.57 60 3
1405.9 17.3 0.6 70 10


1408,9 26,8 0,5 60 10


1411,2 45,4 i 0,41 70 29


1414,6 38.1 ~ 0,76 100 24


1414,7 26,6 0.48 50 2


1419,8 39.7 0.41 70 29


1424,9 35.4 -0.61 10 71





CA 02473814 2004-07-13
-11-
1434,8 41.2 0.48 50 _ 2


1442,8 33,3 0.69 90 _ 21


1444.6 37,8 0.61 90 29
1465.9 28,8 0.53 60 7


1472 ~ 31'2 _0.46 fio- 14
_ -.


1474,9 16,9 0,58 70 12


1482 30.4 0.42 70 28


1484 30,4 0.49 80 31


1487.7 41,4 -0.41 50 91


1490.9 53,4 -0.41 30 71


1493.7 33,7 0.41 70 29
1498,7 34.9 0,46 60 14


1499.9 30.6 0,56 90 34


1501,1 29,5 0.45 50 5


1502.9 16,8 0,68 70 2


1508.9 16,8 0,51 60 9


1511.7 38,4 0,56 80 24


1517.6 54,8 0,48 60 12


1518 26,8 0,52 100 48
1518,9 42,5 0,48 60 12


1520.7 27,9 ~ 0,41 60 19
1527,9 34,7 ; 0.41 70 29


1529.7 54,1 -0.44 40 84


1535 28,3 t 0.68 80 12


1536,6 35 ~ 0.46 60 14


1537.9 31.5 0.52 80 28


1540,7 29,8 0,44 60 16


1547 38.3 0,5 90 40


1548.3 31,1 0.47 90 43


1553.2 54,4 0,48 60 12


1556.8 33.7 0,51 80 29


1567 31.9 0,49 90 41


1567,6 53,9 -0,55 0 55


1588.4 47,9 -0,62 10 72


1589,7 54.3 -0.44 40 84


1591,6 32.6 0,53 60 7


1596.9 34 0,58 80 22


1598,7 28,5 0,48 60 12


1604,3 21,6 0,56 70 14


1604.7 38,1 0,49 80 31


1605.7 53,3 -0,44 30 74


1607.7 41 0.48 60 12


16_11,7 53,2 -0.54 30 84


1612,8 36.8 0,47 80 33


1619,7_ 53.9 -0.52 10 62


1622 19.2 0,6 100 40


1644 18,8 0,41 50 9


1669.9 33,4 0.59 80 21


1671,3_ 25.4 0.42 80 38


1681,6 40 0,59 90 31


1686.8 38.2 0.66 90 24


1692.5 44,2 -0.59 20 79


1695,1 23.6 0,48 60 12





CA 02473814 2004-07-13
-12-
1711 43.3 -0,46 20 66


1713.4 24.6 0,41 60 _
19


1718.5 22.6 0,41 50 9


1723,3 26,5 0,43 60 17
1726 36,3 0,61 70 9


1729.1 37,7 0,41 50 9
1729.2 26 0,66 80 14
1732 51,6 -0.48 30 78


1739.8 35,7 0.49 90 41


1746.2 46,2 ~ -0,54 30 84
1747.7 50,8 -0,47 10 57


1751,4 40,8 ! 0,42 80 38
1752.9 39,9 ~ 0,48 70 22


1763 24,4 ~ 0,68 90 22


1770,4 45.4 0,52 100 48


1_772.6 28,5 ~ 0.44 _ 16
_ -- - 60
- ~ ~ -


1776.1 43.6 # 40 83
_0 43


1777,6 28.6 ! 0,73 90 17


1783.4 29,2 ' 0.51 70 19


1784,9 31,4 ~ 0.47 50 3
1786,9 35,9 0,53 70 17


1788,6 31 0,49 90 41


1792,4 42,3 0,59 80 21


1794,9 40.4 0.4 80 40
1804.7 34 0.45 100 55


1808.1 45.6 0.55 60 5


1810.1 31.8 0,41 60 19


1811.3 31,3 0,52 90 38


1813,4 54.7 -0.43 10 53
1815.1 39,3 0.41 60 19


1815.2 27,7 0,44 60 16


1820.1 31,8 0,57 100 43


1821.2 18.2 0,45 50 5


1821,5 42,1 0.46 70 24


1822.9 40.7 -0.73 10 83


1824,3 37 -0.59 20 79


1831.7 25.2 0.43 50 7


1831.9 41,5 0,61 70 9


1844,2 34.6 0.62 90 28


1847,8 57 -0.73 20 93


1849,6 37,2 -0.41 40 81


_1851,2 31,6 0,52 90 38


1853 31.2 0.58 80 22


1853.4 18.3 0,5 50 0


1853,6 46.7 0.57 60 3


1854.2 28.8 0,43 50 7


1856,8 56.3 -0,59 10 69


1857.1 39 0,51 80 29


1864.6 28,6 0,43 60 17


1867 31,8 0,49 80 31


__1870,5 16.1 0,45 50 5


1_871,7 43,2 0,65 70 5


1881,4 34,3 0.47 80 33





CA 02473814 2004-07-13
- l~ -
1889,8 _4_6_.4_ -0,67____ 30 97


1891.6 32.3 0.58 80 22
1894,9 22 0,71 90 19


1894,9 56 -0,46 20 66


1898,7 26.5 0,46 60 14


1900,7 30,4 -0.63 20 83


1902,8 33.1 0.53 70 17


1904 27,5 0,48 50 2


1904.3 43,2 0,41 50 9


1916.8 44,7 -0,46 20 66


1920.5 46,1 0.44 60 16


1920,7 30.6 0,45 90 45


1925,3 52,5 0,57 90 33


1928.4 33,2 0,48 70 22


1933,9 32,8 -0,41 50 91


1934,2 16,1 0,78 80 2


19_36.5 46_._6_ -0._47_ 20 67
- - -


1936,7 32.8 x.51 80 29


1944.2 47 -0.66 20 86


1950,9 34.5 0.59 90 31


1951,1 53 -0,54 10 64


1966,3 25,1 0,6 70 10


1973.7 57,1 -0.49 10 59


1977,4 42.9 -0.48 40 88


1982.9 32,2 0.46 70 24
1989,3 43,7 0,54 70 16


1990,8 47.3 -0,83 0 83


1999,4 35,6 0.4 80 40


2005,3 39,6 0,49 80 31


2013,8 45,3 -0,47 20 67


2022,6 34,6 0,48 70 ~ 22


2028.4 29.9 0.66 90 24


2030.8 46.5 -0,56 30 86


2033,5 27,5 0,51 60 9


2042 26.4 0,52 100 48


2042,5 40.7 0,49 70 21


2047 45.4 -0,48 50 98


2048,2 33,1 -0,6 40 100


2057,2 36.3 0,43 100 57


2063 24.3 0,6 60 0


2065,3 20,9 0,57 60 3


2077,3 35.8 ~ -0.42 10 52


2092,5 41,3 0.44 60 16


2099.2 36.9 0,54 80 26


2105.4 32,5 0,56 70 14


2114.9 42 0,48 70 22


_2117.1 57.1 -0.68 10 78


2121 26.9 0,61 80 19


2127,2 39,6 0,61 90 29


2140.1 26,8 0.48 60 12


2144,3 22 0.42 70 28


2146,3 25.8 0,57 60 3


2147,2 38,4 0.69 90 21





CA 02473814 2004-07-13
-14-
2163.4 27.6 0,6 70 10


2174.,4 24.6 0,58 80 22


2178,5 21,4 0.41 50 9


2178,7 47.5 -0,4 20 60


2182,5 27.6 0.46 70 24


2200.3 47 0,5 50 0
-


2210,7 2~:7 0.58 80 22


2212,9 46,3 -0,44 40 _ 84


2221,1 40,7 -0,44 20 ' 64


2223,5 22,6 0,41 50 9


2228,1 25.9 0.5 90 40


2233 31,1 -0,65 30 95


2257.2 46.6 -0,4 60 100


2258.9 33,6 0,62 100 38


2290.7 36,2 0.45 50 _ 5


2291,1 __21,9_ 0,45 50 5


2322.5 47,1 0.55 60 5


2334,2 41,2 0.45 50 5


2338.2 40,4 0.53 60 7


2367,7 43,2 -0,43 40 83


2375,2 36,5 0,42 80 38


2391.2 24,3 0,48 60 12


2409.1 41,9 0,49 90 41
- .


2423.1 27,4 ~ 0,42 70 28


2426.5 38,5 0,49 80 31


2427.4 24 0,59 90 31


2429,9 39.3 ' -0,46 30 76


2432,2 38.3 0,76 90 14


2435 21.6 0.48 50 2


2438.3 52.6 0,46 60 14


2443.4 31,9 -0,44 40 84


2464 47,2 -0,52 10 62


2465 22.8 0.65 70 5


2473,4 41,9 0,51 60 9


2490.5 43 0,43 60 17


2490.7 26.7 0,42 70 28


2493,6 24.6 0,66 80 14


2529,2 41.4 -0,5 10 60


2536.6 24,8 0,51 60 9


2540.5 25,5 0,5 60 10


2542,6 42,1 0.41 50 9


2568,9 26.9 0,41 70 29


2570.5 57.1 -0,58 20 78


2573.7 16,3 0,51 60 9


2584 43,8 -0,67 30 97


2591,5 37,7 -0.4 10 50


2592,5 56,6 -0.42 20 62


2593,4 25 0,44 60 16


2608,6 37.6 0,43 90 47


2614.1 22.5 0,53 70 17


2619,7 2_2_,9_ 0,47 50 3


2621.4 25.8 0,48 60 12


2627,4 44.8 -0.41 50 91





CA 02473814 2004-07-13
-15-
2646.7 21.9 0,53 60 7


2660,8 27,1 0.51 70 19


_26_77,6 23,6 0,5 60 10


2679,5 35 -0.5 50 100


2687,4 41,9_ -0.4 60 100


2690.3 24.8 0,45 50 5


2713,2 41,3 -0.52 10 62


2720,6 39.5 0.47 50 3


2752.8 25,3 0,44 70 26


2767,4 31,4 -0.55 40 95


2780.4 28.3 0.46 60 14


2793.7 36,3 0,64 80 16


2825,4 36,5_ ~-0,48 50 98


2830.9 33.2 0,51 70 19


__2_841,6_37,1 -0,42 30 72


2854.4 43,8 -0,47 50 97


2883,6 28,9 0,63 80 17


2892,2_ 32,1 0,51 80 29


2898_.5__ 42,3 -0.44 40 84


_2902,9 42,1 0.48 _ 12
60


2911.7 36.8 -0.54 30 84


2918 42.2 -0.54 20 74


2937.1 26.6 0.51 60 9


2945.1_ 22,6 0.41 50 9


2973.7 34.9 -0.58 30 88


2978 26,3 -0,53 30 83


2986.9 47,3 -0.41 40 81


2990.4 33,6 -0.57 10 67


3012,1 39,4 -0,4 60 100


3017.7 46,8 -0,5 10 60


3022,8 33.8 -0.57 40 97


3038.1 33.7 -0.51 30 81


3047.7 35.9 ~ -0,49 30 79


3057,1 56.4 -0.54 30 84


3058,8 35,5 -0.46 40 86


3080,2 31.7 -0.4 20 60


3098.8 42,6 -0.4 60 100


31_08._8_ 44,7 -0,45 50 95


3121.4 42,5 -0,5 50 100


3137 37 -0.53 30 83


3139.4 43.7 - -0,58 20 78


3152,6 38.2 -0,4 60 100


3158.8 43,3 -0,51 40 91


3166,2 41,2 -0,43 50 93


3177.4 22.3 -0.52 20 72


3187.7 48,6 -0.41 40 81


3209.2 34,3 -0,67 30 97


3255,8 42,9 -0.64 20 84


3262 31,5 -0,46 40 86


3281 36.8 -0.78 20 98


3290,9 36.9 -0,53 40 93


3293.2 54,2 -0,47 50 97


3295,8 38,4 -0,48 50 98





CA 02473814 2004-07-13
-16-
3308.6 21,3 0.57 60 3


3315,1 54,1 -0.61 10 71


3319.3 46,2 -0.45 50 95


3322,8 27.3 -0,48 30 78


3333,4 23,3 -0,68 20 88


3334,6 41,7 -0,56 30 86


3337,4 36,2 -0.58 30 88


3343,8 43,8 -0,61 30 91


3360,1 44,3 -0,4 60 100


3376,2 45,2 -0.47 50 97


3402,4 33,8 -0,48 50 98


3405.7 37,8 -0,58 40 98


3421,8 21,1 0.47 50 3


3422,5 38.7 -0,6 30 90
3436 26.4 -0,61 10 71


3503.3 23.2 -0.49 10 59


3530,9 36,8 -0,51 30 81


3547,3 38.5 -0,4 10 50


3583,3 25.2 -0,9 0 90


3589.5 39,1 -0.8 10 90


3631,2 33.1 -0,51 20 71


3634,9 42,6 -0.49 30 79


3682,4 42.8 -0.44 30 74


3686,1 32.6 -0.73 10 83


3697.4 38.8 -0.43 10 53


3701,8 43,4 -0.62 10 72


3707 31,9 -0,76 0 76


3719.6 44,7 -0.43 40 83


3723,3 32,5 -0.77 20 97


3760.8 25,9 -0.49 20 69


3802.7 46.2 -0.47 10 57


3816.7 32,2 -0,56 10 66


3852.2 36.9 -0,41 40 81


3871,7 42.9 -0.54 10 64


3946,9 33.1 -0,63 30 93


3955,9 23.6 0,41 50 9


3969.6 31,3 -0,46 40 86


3987 30.5 -0,47 50 97


4026,2 30,5 -0,53 0 53


4044.7 31,2 -0,56 30 86


4055.2 24,1 0,54 70 16


4154,2 23,7 0,66 80 14


4170.6 46.1 -0.42 10 52


4241.2 24,4 0,66 80 14


4283,1 24,3 0,41 50 9


4306.5 41.4 -0,4 20 60


4335,8 27.1 0.43 50 7


4527,7 26 0,48 50 2


4594,6 20.6 0,45 50 5


4654,8 38,8 -0,42 10 52


4713.7 26,9 0,65 70 5


4748,5 25.4 -0.45 50 95


4772,1 28,9 -0.42 10 52





CA 02473814 2004-07-13
-17-
5213.8 36.8 -0,4 10 50


5229,1 39.9 -0,52 0 52


5428,4 33.5 -0.44 30 74


5575.8 35.7 -0.52 10 62


5845;8 21,8 0,5 50 0


6171.5 39.6 -0.63 30 93


6212,4 30.6 -0.49 10 59


6238.6 30,9 -0,56 20 76


_75_56.6 26,2 0,44 60 16


7885.4 20 9 0,45 50 5


8054,8 16.7 0,61 80 19


8341,2 16.6 0.53 60 7


8765,9 17,6 0,47 80 33


9076 23 s 0.5 60 10


9223.1 22,8 's 0.53 60 7


9465.1 23,3 E 0,5 50 0


98_68.8 29.5 -0,68 10 78


9933,5 18.4 0.47 50 3


10046.3 18.1 0.61 80 19


10518,8 20.9 0,51 70 19


Table 3:
mo__lecularmi ratio_n discriminationfre uenc fre uenc


FSCiS MCD


830,5 25,3 0,49 80 31


865,4 35,5 0,43 80 38


907,4 27,5 0,41 60 19


1005,5 35 0,45 70 25


1008,5 34,4 -0,45 30 75


1015,6 38,2 0,47 60 13


1026,5 33,2 -0,4 _ 50
10


1041,5 51,6 -0,42 20 63


1055,6 36,4 0,41 60 19


1085,6 50,8 -0,42 20 63


1088,6 37,4 0,49 80 31


1107,5 40,2 -0,45 30 75


1128,5 44,3 0,41 60 19


1138,6 22,9 -0,4 10 50


1160,6 [ 48,8 -0,44 50 94


1191,6 50,5 -0,49 20 69


1199,6 31 -0,63 0 63


1207,7 36,6 0,41 60 _
19


1208,6 38,6 0,41 60 19


1211,6 31,3 0,43 80 38


1224,7 33,6 -0,44 50 94


1270,6 25,7 0,41 60 19


1274,6 50,7 -0,44 50 94


1282,7 38,4 0,43 80 38


1294,6 54,4 0,45 70 25


1304,8 __ 24,6 0,44 50 6


1305,9 33,4 0,51 70 19


1308,6 53,6 -0,45 30 75




CA 02473814 2004-07-13
-18-
1377,7 25,4 0,45 _ 70 25
~


1390,7 41,1 _0,4 90 50


1404,9 29,4 0,43 80 38


1493,7 33,7 0,51 70 19


1518,9 42,5 0,41 60 19


1581 37,8 -0,44 50 94


1594,8 54,8 -0,4 60 100


1607,7 41 0,41 60 19


1650,7 25,4 -0,46 10 56


1695,7 54,7 -0,4 10 50


1766,6 44,9 -0,41 40 81


1826,9 50,8 -0,59 10 69


1880,3 57,4 -0,42 _ 20 63


1887,8 33,8 0,4 __ 90 50


1900,7 30,4 -0,61 20 81


1925,3 52,5 0,59 90 31


1950,9 34,5 0,59 90 31


1992,9 48,5 0,44 50 6
-- -..


2005,3 39 6 0,43 80 38


2011,5 42 -0,64 _ 94
30


2048,2 33,1 -0,41 40 81


2063 24,3 0,41 60 19


2077,3 35,8 -0,59 10 69


2121 26,9 0,43 80 38


2163,4 27,6 0,51 70 19


2174,4 24,6 0,43 80 38


2258,9 33,6 0,75 100 25


2412,3 42,7 -0,42 20 63


2453,2 49,7 -0,42 20 63


2487,9 38 0,41 60 19


2570,5 57,1 -0,42 20 63


2679,5 35 -0,44 50 94


2690,3 24,8 0,5 50 0


2819,4 32,2 0,44 50 6


2864,7 29,1 -0,49 20 69


2883,6 28,9 0,55 80 25


2889,2 20,2 0,41 60 19


2918 42,2 -0,68 20 88


2986,9 47,3 -0,41 40 81


3209,2 34,3 -0,51 30 81


3255,8 42,9 -0,42 20 63


3315,1 54,1 -0,4 10 50


3402,4 33,8 -0,44 50 94


3583,3 25,2 -0,5 0 50


4335,8 27,1 0,44 _ 6
50


9182 17,1 -0,42 20 63


Table 4:
molecular migration discrimination fre uenc [%]
weight [Da] time [min] factor FSGS NIGN


CA 02473814 2004-07-13
-19-
819,5 35,7 -0,47 20 67


909,4 40,3 -0,4 _ 60 100


939,6 33,1 0,59 70 11


978,5 23,9 -0,4 10 50


1017,4 36,6 -0,43 40 83


1081,7 29,6 0,49 60 11


1201,5 51,6 0,43 60 17


1282,7 38,4 0,47 80 33


1284,8 55,1 -0,4 10 50


1305,9 33,4 0,42 70 28


1338,7 29,6 0,41 80 39


1341,8 33,1 -0,43 40 83


1359,5 47,4 0,53 70 17


1394,3 48,1 0,43 60 17


1403,8 34,4 0,43 60 17


1423,6 22,3 -0,47 20 67


1490,7 33,7 -0,47 20 67


1493,5 57 -0,46 10 56


1497,9 26,7 -0,48 30 78


1504,4 30,5 -0,42 30 72


1517,6 54,8 ,4 60 17
3
0


1526,4 39,4 _ 30 72
_
-0,42


1529,5 32,4 0,43 60 17


1576,4 42,5 0,48 70 22


1591,7 51,2 0,44 100 56


1595,4 31 -0,48 30 78


1692,4 30,4 -0,41 20 61


1734,6 27,2 -0,48 30 78


1768,9 44,7 0,63 80 17


1790,8 38,8 0,4 90 50


1802,5 25,6 -0,42 30 72


1844,2 34,6 0,4 90 50


1883 29,1 0,44 50 6


1885,7__ 57,5 0,42 _ 28
1900,7 3pj4 _.=O'47 _. 70 _ 67.
20_


1920,5 46,1 0,49 60 11


1925,3 52,5 0,57 90 33
1933,9 32,8 0,44 50 6


1971;5 18,9 -0,47 20 67


1986,6 35,8 -0,42 30 72
2011,5 42 -0,42 30 72
2015,1 49,6 -0,42 30 72
2079,7 21,8 -0,51 10 61


2121 26,9 0,47 80 33
2129,5 35,1 0,43 60 17


2146,3 25,8 -0,4 60 100


2274 37 -0,4 10 50
2292,4 35,3 -0,48 30 78
2299,9 34,3 -0,5 0 50


2312,5 22,9 -0,63 20 83


2338,2 40,4 0,43 60 17


2338,6 26 -0,49 40 89


2356,3 24 -0,43 40 83
2421 28,7 -0,44 50 94




CA 02473814 2004-07-13
-20-
2449,3 28,3 -0,53 30 83


2451,7 35,5 -0,43 40 _ 83


2453,6 32 -0,53 30 83


2469,3 32,5 -0,51 10 61


2471,7 23,8 -0,42 30 72


2525,5 35,6 0,68 90 22


2566,4 22,2 -0,42 30 72


2591,5 37,7 -0,4 10 50


2607 47,6 0,48 70 22


2639,6 45,2 -0,46 10 56


2665,3 39,4 -0,49 40 89


2712,9 22,6 -0,42 30 72


2758,5 40,9 0,42 70 28


2912,9 57,5 -0,4 10 50


3041,2 45 0,41 80 39


3107,2 26,4 -0,4 10 50


3182,9 34,3 0,44 50 6


3313,8 31,6 -0,48 30 78


3479,3 48,5 0,53 70 17


4827,1 27,3 -0,43 40 83


5829,7 20,8 -0,41 20 61


8216,9 16,8 -0,4 10 50


8371,2 15,8 -0,41 20 61


8466,3 18 -0,51 10 61


8518,7 15,7 -0,48 30 78


8578,4 17 -0,47 20 67


9182 17,1 -0,69 20 89


Table 5:
molecular migration discriminationfre uenc
weight [Da] time [min]factor FSGS MCD
+ MGN


939,6 33,1 0,49 70 21


1282,7 38,4 - _0,45 $0 35


1305,9 33,4 0,46 70 24


1359,5 47,4 0,44 70 26


1493,7 33,7 0,41 70 29


1650,7 25,4 -0,4 10 50


1734,6 27,2 -0,41 30 71
1900,7 30,4 -0,54 20 74


1925,3 52,5 0,58 90 32


2011,5 42 -0,52 30 82


2121 26,9 0,45 80 35
2258,9 33,6 0,41 100 59


2312,5 22,9 -0,48 20 68


2449,3 28,3 -0,41 30 71
2525,5 35,6 0,49 90 41
2607 47,6 0,41 70 29


2690,3 24,8 0,41 50 9


2918 42,2 -0,51 20 71




CA 02473814 2004-07-13
-2I -
9182 17,1 -0,56 20 ~ - - 76~
Table 6:
molecularMigrationdiscriminationfrequenc
time [%]


weight [min] factor MCD controt
[Da]


836,5 35 0,59 75 16


862,4 48,7 0,44 56 12


866,4 37,9 0,41 56 16


866,5 23,1 0,55 56 2


870,4 33,9 0,43 50 7
- _
_


876,4 48,9 -0,61 38 98
_
-_


881,5 25,7 0,46 75 29


882,6 36,5 -0,64 31 95


888,6 29,9 -0,47 6 53


903,4 46,8 -0,49 6 55


914,5 34,3 0,47 50 3


925,4 50,7 0;61 75 14


943,5 30 0,47 75 28


950,5 36 0,51 56 5


956,4 49,5 -0,48 13 60


958,5 32,5 0,46 69 22


974,5 37,9 0,41 50 9


988,5 33,9 0,43 50 7


990,6 32 0;44 63 19


991,4 37,7 0,42 56 14


1000,5 34 -0,51 44 95


1006,4 35,7 -0,4 38 78


1010,6 50,8 -0,45 19 64


1010,6 30,6 -0,52 31 83


1033,6 39,1 0,41 50 9


1034,5 31,4 0,47 50 3


1046,6 38,6 -0;59 38 97


1047,6 30,4 -0,47 38 84


1085,6 50,8 0,49 63 14


1102,6 32,9 0,44 56 12


1104,6 43,3 -0,45 6 52


1108,6 29,8 0,42 81 40


1110,4 46,9 -0,46 25 71


1122,5 50,2 -0,41 25 66


1135,6 42,7 -0,53 13 66


1138,6 39,3 0,7 88 17


1138,6 22,9 0,48 50 2


1139,6 32,2 0,49 56 7


1141,6 38 -0,61 6 67


1159,6 39 -0,56 25 81


1171,6 32,8 0,8 81 2


1182,6 47,2 -0,41 _ 66
25


1191,8 18,3 0,46 56 10


1199,6 31 0,61 63 2


1203,7 24,7 -0,51 6 57


1219,6 37,3 0,48 69 21


1223,5 51,6 -0,65 25 90


1233,7 49,6 0,45 50 5


1237,7 41,6 -0,42 25 67


1246,7 30,5 -0,41 25 66


1256,6 53,4 0,49 63 14
1264,7 26,7 0,66 75 9




CA 02473814 2004-07-13
-22-
1268,6 53,7 -0,45 6 52


1269,7 39,8 0,44 63 19


1270,5 52,5 -0,49 6 55


1274,6 50,7 0,49 94 45


1280,6 51,9 -0,5 13 62


1292,5 53 -0,49 38 86


1296,6 53,8 0,53 56 3


1302,7 31,8 0,55 88 33


1310,7 36,8 0,41 56 16


1311,8 31,5 0,44 63 19


1324,2 40,5 0,6 69 9


1324,5 54,3 0,45 63 17


1325,5 35,2 0,55 81 26


1333,8 38,8 0,52 69 17


1338,7 47,2 0,86 88 2


1338,7 29,6 0,52 63 10


1350,7 50,3 -0,44 6 50


1354,8 45,6 0,62 100 38


1365 22,3 0,49 63 14


1371,8 19,3 0,49 75 26


1389,8 19,5 0,41 75 34


1401,8 46,2 -0,5 13 62


1414,6 38,1 0,57 81 24


1415,7 33,3 0,51 56 5


1424,9 35,4 -0,52 19 71


1442,8 33,3 0,61 81 21


1444,6 37,8 0,46 75 29


1448,8 30,3 0,42 75 33


1472,1 31,2 0,42 56 14


1474,9 16,9 0,63 75 12


1482 30,4 0,47 75 28


1484 30,4 0,5 81 31


1486,5 30,6 0,61 81 21


1499,9 30,6 0,53 88 34


1502,8 28,8 0, 81 31
5


1502,9 16,8 _ 56 2
0,55


1508,9 16,8 0,54 63 9


1511,7 38,4 0,7 94 24


1535 28,3 0,57 69 12


1548,3 31,1 U,44 88 43


1556,8 33,7 0,52 81 29


1561,9 28,1 0,46 88 41


1567,6 53,9 -0,55 0 55


1573,8 40,4 0,43 88 45


1574,3 53,4 -0,41 13 53


1588,4 47,9 -0,6 13 72


1591,6 32,6 _ 56 7
0,49


1596,9 34 0,53 75 22


1604,3 21,6 0,55 69 14


1611,7 53,2 -0,41 44 84


1612,8 36,8 0, 88 33
55__


1622 19,2 _ 81 40
_
0
,42


1629,6 49,6 _ 50 3
0,47 -.


1635,2 27,8 0,41 75 34


1644 18,8 0,41 50 9


1658,4 39 0,44 88 43


1669,9 33,4 0,48 69 21
1671,3 42,6 0,42 56 14


1676 25,3 0,44 56 12




CA 02473814 2004-07-13
- 23 -
1681,6 40 0,.56 88 31


1686,8 38,2 0,63 88 24


1692,4 30,4 0,41 56 16


1699,1 41,9 0,63 88 24


1718,5 22,6 0,48 56 9
1746,2 46,2 -0,53 31 84


1747,7 50,8 -0,51 6 57


1751,4 40,8 0,43 81 38


1752,9 39,9 0,46 69 22


1766,6 44,9 0,52 81 29


1776,1 43,6 -0,45 38 83
1777,6 28,6 0,58 75 17


1804,7 34 0,45 100 55


1811,3 31,3 0,5 88 38


1813,4 54,7 -0,53 0 53


1815,2 27,7 0,41 56 16
1820,1 31,8 0,44 88 43


1821,2 18,2 0,45 50 5


1822,9 40,7 -0,52 31 83


1824,3 37 _p,42 3$ 79.


1831,9 41,5 0,54 63 9


1847,8 57 -0,62 31 93


1851,2 31,6 0,43 81 38


1853 31,2 0,4 63 22


1854,9 53,6 -0,44 6 50


1856,8 56,3 -0,44 25 69


1864,6 28;6 0,64 81 17


1867 31,8 0,56 88 31


1889,8 46,4 -0,53 44 97


1894,9 22 0,56 75 19


1896,8 53,3 -0,43 13 55


1909,7 47,9 0,49 63 14


1913,4 30,1 0,46 56 10


1916,8 44,7 -0,59 6 66


1934,2 16,1 0,48 50 2


1944,2 47 -0,61 25 86


1951,1 53 -0,45 19 64


1955,3 48,4 0,44 63 19


1966,3 25,1 0,65 . 75 10


1973,7 57,1 -0,46 13 59


1982,9 32,2 0,57 81 24


1989,3 43,7 0,66 81 16


1990,8 47,3 -0,7 13 83


2011,5 42 0,64 94 29


2017,6 33,2 0,45 81 36


2030,4 31,7 -0,44 38 81


2030,8 46,5 -0,61 25 86


_2047 45,4 -0,42 56 98


2050,8 38,2 0,47 81 34


2092,5 41,3 0,66 81 16


2098,3 52 0,5 69 19


2099,2 36,9 0,49 75 26


2103,6 26,7 0,44 88 43


2106,1 46,1 0,41 56 16


2117,1 57,1 -0,4 38 78


2129,5 35,1 -0,47 50 97


2130,3 18,4 0,42 56 14


2139,3 36,9 0,41 56 16


2146,3 25,8 0,59 63 3




CA 02473814 2004-07-13
-24-
2151,6 42,6 0,44 56 _12


2157,2 24,4 __0,54 63 _ 9
~ ~


2182,5 27,6 0,51 75 24


2189,1 40,9 -0,48 19 67


2207,2 41,9 0,48 69 21


2210,7 25,7 0,59 81 22
2217,7 41,9 0,53 88 34


2223,5 22,6 0,54 63 9


2228,1 25,9 0,48 88 40


2238,4 46,3 -0,41 44 84


2281,7 45,6 -0,5 31 81


2426,5 38,5 0,56 88 31


2432,2 38,3 0,55 69 14


2464 47,2 -0,5 13 62


2465 22,8 0,51 56 5


2522,9 24,4 0,42 63 21


2529,2 41,4 -0,42 19 60
2535 37,7 0,42 81 40


2540,5 25,5 0,58 69 10
2548,2 35,1 -0,45 38 83


2566,4 22,2 0,49 56 7


2593,4 25 0'41 56 _ 1.~


2621,4 25,8 0,5 63 12


2644,1 32,5 -0,43 50 93


2698,4 32,1 -0,48 31 79


2713,2 41,3 -0,43 19 62
2752,8 25,3 0,49 75 26


2790,3 26,8 0,41 56 16


27 36,3 0,66 81 16
93
,7


_ 37,2 -0,46 31 78
_
2809,1


__ 30,4 0,43 69 26
2921,4


2933,8 39,4 -0,47 6 53


2973,7 34,9 -0,5 38 88


_3007,5 _ -0,48 19 67
30,5


30 46,8 -0,42 19 60
17,7


_ 43,7 -0,4 38 78
3139,4


3179,2 44,3 0,41 75 34


3262 31,5 -0,49 38 86


3281 36,8 -0,48 50 98


3282 49,4 -0,45 50 95


3290,9 36,9 -0,56 38 93


3295,8 38;4 -0,48 50 98


3333,4 23,3 -0,5 38 88


3334,6 41,7 -0,42 44 86


3343,8 43,8 -0,41 50 91


3433,3 44,5 -0,42 56 98


3530,9 36,8 -0,5 31 81


3589,5 39,1 -0,58 31 90


3631,2 33,1 -0,52 19 71


3686,1 32,6 -0,7 13 83


3697,4 38,8 -0,41 13 53


3701,8 43,4 -0,54 19 72


3707 31,9 -0,63 13 76


3723,3 32,5 -0,47 50 97


3760,8 25,9 -0,5 19 69


3816,7 32,2 -0,47 19 66


4154,2 23,7 0,42 56 14


4170,6 46,1 -0,45 6 52


4241,2 24,4 0,67 81 14




CA 02473814 2004-07-13
- 25 -
4283,1 24,3 ___0,54 63 9
4707,5 20,5 _0_,42 56 14
_


4713,7 26,9 0,45 50 5
4748,5 25,4 -0,57 38 95


4772 28,9 -0,4 6 52
,1 5


_ -- 36-8 _ 6 50
__ _~ 44
_ 5213,8


7409,9 26,2 0,44 56 12


7556,6 26,2 0,53 69 16


8054,8 16,7 0,5 _ 19
69


8765,9 17,6 0,48 81 33


9076 23 0,58 69 10


9182 17,1 0,54 63 9


9223,1 _22,8 0,56 63 7


9_8_68_,8_29,5 -0 25 78
,53


10046,3 18,1 _ 81 19
0,62


10390,1 20,2 0,5 63 12


10518,8 20,9 0,62 81 19


Table 7:
molecular migration discriminationfrequency
time [%]


weight [min] factor MCD MGN
[Da]


814,5 28,8 -0,46 38 83


819,5 35,7 -0,48 19 67


856,5 28,9 0,42 75 33


863,4 28,8 -0,54 13 67


864,5 37,3 -0,48 19 67


879,6 26,9 0,72 94 22


882,6 36,5 -0,41 31 72


909,4 40,3 -0,56 44 100


928,4 49,4 0,53 81 28


934,5 33,9 -0,41 31 72


935,6 36,6 0,46 63 17


946,5 46,8 0,47 69 22


952,5 32 -0,46 38 83


1005,5 35 -0,42 25 67


1008,5 34,4 0,53 75 22


1015,6 38,2 -0,71 13 83


1017,4 36,6 -0,52 31 83


1022,5 39,1 -0,52 31 83


1028,6 37,8 0,47 69 22


1073,6 34,7 -0,56 44 100


1085,6 50,8 0,51 63 11


1108,5 50,1 0,45 56 11


1113,6 33,7 -0,48 19 67


1138,6 22,9 0,44 50 6


1147,6 49,7 0,46 63 17


1152,5 40,7 -0,65 19 83


1208,6 38,6 -0,42 19 61


1211,6 31,3 -0,46 38 83


1213,6 50 -0,43 13 56


1224,7 33,6 0,6 94 33


1225,7 41,3 -0,42 25 67


1270,6 25,7 -0,48 19 67


1277,6 50 0,46 63 17


1279,7 38,3 -0,63 31 94


1283,9 28,9 -0,48 19 67


1301,7 34 -0,43 13 56




CA 02473814 2004-07-13
-26-
1319,9 34,8 -0,46 38 83


1329,8 37,5 -0,47 25 72


1337,6 52 0,47 69 22


1341,8 33,1 -0,58 25 83


1350,8 26,8 -0,42 19 61


1365 22,3 0,4 63 22


1381,1 32,3 -0,63 31 94


1398,9 30,5 -0,44 50 94


1404,9 29,4 -0,63 38 100


1423,6 22,3 -0,48 19 67


1426,8 38,7 -0,42 25 67


1433 33,7 -0,53 19 72


1465,9 28,8 -0,45 44 89


1482,8 36,3 -0,46 38 83


1487,7 41,4 0,54 88 33


1490,7 33,7 -0,48 19 67


1512,8 35,9 0,41 69 28


1527,9 34,7 -0,44 50 94


1543,8 34,9 -0,52 31 83


1558,1 23,4 -0,42 19 61


1560,5 39,5 -0,46 38 83


1569,8 48,3 0;5 50 0


1574,8 33,9 -0,58 31 89


1593,8 36,7 0,41 69 28


1595,4 31 -0,4 38 78


1602,8 58,1 0,51 63 11


1605,9 23,7 -0,65 13 78


1607,7 41 -0,42 19 61


1612,8 26,3 -0,43 13 56


1623,3 41,4 -0,47 31 78


1671,3 42,6 0,45 56 11


1726 36,3 -0,51 44 94


1729,2 26 -0,45 44 89


1744,1 34,3 -0,63 38 100


1768,9 44,7 0,52 69 17


1774,6 36,5 -0,47 31 78


1786,9 35,9 -0,41 31 72


1799 28,8 -0,47 25 72


1802,5 25,6 -0,53 19 72


1826,9 50,8 0,52 69 17


1839,1 35,5 -0,44 50 94


1857,1 39 -0,44 50 94


1859,4 22,8 -0,42 25 67


1863,8 57,5 0,42 81 39


1876,2 40,1 -0,51 38 89


18_7_8,7 49,9 0,47 75 28


1880,3 57,4 0,51 63 11


1883 29,1 0,44 50 6


1885,7 57,5 0,47 75 28


1887,8 33,8 -0,5 50 100


1898,7 26,5 -0,52 31 83


1924,2 32,9 -0,64 25 89


1933,9 32,8 0,57 63 6


1936,7 32,8 -0,44 56 100


1949,1 38,5 0,43 88 44


1950,9 34,5 -0,58 31 89


1971,5 18,9 -0,48 19 67


1977,4 42,9 0,4 63 22


1988,9 28,8 -0 4 38 78
~




CA 02473814 2004-07-13
-27-
2005,3 39,6 -0,46 38 83


2011,3_ 29 -0,43 13 56


2033,5 27,5 -0,53 25 _
78


2035,6 30,9 -0,54 13 67


2065,3 20,9 -0,47 25 72


2077,3 35,8 0,41 69 28


2109,3 27,9 -0,51 44 94


2140,1 26,8 -0;51 38 89


2152,7 29,5 -0,51 44 94


2160,4 27,9 -0;49 6 56


2163,4 27;6 -0,48 19 67


2167,3 27,8 -0,41 31 72


2174,4 24,6 -0,51 38 89


2178,5 21,4 -0,4 38 78


2189,1 40,9 -0,48 19 67


2258,9 33,6 -0,64 25 89


2274 37 -0,44 6 50


2288,8 41,4 -0,65 13 78


2291,1 21,9 -0,47 25 72


2292,4 35,3 -0,4 38 78


2308,9 26,2 -0,46 38 83


2332,4 35,4 -0,54 13 67


2341,2 26,3 -0,49 6 56


2356,3 24 -0,46 38 83


2367,7 43,2 0,58 75 17


2380 39,6 -0,51 44 94


2391,2 24,3 -0,44 50 94


2423,1 27,4 -0,45 44 89


2434,4 34,7 -0,44 6 50


2446,2 24,7 -0,42 19 61


2451,7 35,5 -0,46 38 83


2453,6 32 -0,52 31 83


2453,8 20,4 -0,49 6 56


2455,6 27,7 -0,41 31 72


2461,1 40,5 -0,47 25 72


2469,3 32,5 -0,42 19 61


2471,7 23,8 -0,41 31 72


2475,5 22,3 -0,42 19 61


2480,2 47,2 0,4 63 22


2483,8 19,6 -0,47 25 72


2493,6 24,6 -0,5 50 100


2500,3 30,4 0,53 75 22


2518,7 38,9 -0,46 38 83


2521,3 48,3 -0,49 13 61


2525,5 35,6 0,4 63 22


2527,3 40,8 -0,53 19 72


2553,7 24,7 -0;42 19 61


2573,7 16,3 -0,45 44 89


2579,5 15,2 -0,48 19 67


2608,6 57,7 0,45 56 11


2614,1 22,5 -0,47 31 78


2619,6 38,3 -0,42 19 61


2642,4 40,9 0,46 63 17


2660,8 27,1 -0,47 31 78


2665,3 39,4 -0,58 31 89


2666 23 -0,43 13 56


2677,6 23,6 -0,51 44 94


2701 34,8 0,4 63 22


2784,3 45,2 -0,59 19 78




CA 02473814 2004-07-13
-2~-
2825,4 36,5 0,49 88 39


2830,9 33,2 -0,57 38 _
~ 94


2864,7 29,1 0,52 69 17


2889,2 20,2 -0,42 19 61


2902,9 42,1 -0,42 25 67


2912,9 57,5 -0,44 6 50


2921,4 30,4 0,52 69 17


2940,5 40,4 -0,4 38 78


3041,2 45 0,42 81 39


3044,8 48,6 0,4 63 22


3082,3 43,1 0,42 75 33


3169 37,5 0,42 75 33


3205,8 28,3 0,53 75 22


3209,2 34,3 0,48 81 33


3255,8 42,9 0,4 63 22


3256,3 23,1 -0,48 19 67


3303,2 38,6 0,44 50 6


3308,6 21,3 -0,47 31 78


3313,8 31,6 -0,53 25 78


3325,5 43,5 0,44 50 6


3336,8 53,8 0,51 56 6


3405,7 37,8 0,46 63 17


3422,5 38,7 0,45 56 11


3479,3 48,5 0,58 75 17


3578,2 32,5 -0,53 19 72


3881,9 26,2 -0,42 19 61


3969,6 31,3 0,45 56 11


4183,7 26,6 -0,47 31 78


4290,8 41,1 0,4 63 22


_ 4527,7 26 -0,53 19 72


4565,8 __25,1 -0,44 6 50


4719,5 39,3 -0,44 6 50


4827,1 27,3 -0,58 25 83


5112,9 33,1 -0,5 0 50


5829,7 20,8 -0,49 13 61


6106,5 27 -0,56 0 56


7885,4 20,9 -0,49 13 61


8341,2 16,6 -0,57 38 94


8371,2 15,8 -0,49 13 61


8466,3 18 -0,42 19 61


8518,7 15,7 -0,53 25 78


8578,4 17 -0,48 19 67


9335,5 17,5 -0,41 31 72


9465,1 23,3 -0,49 13 61


9944,2 16,7 -0,48 19 67


10949,7 26,3 -0,56 0 56


Table 8:
molecular migration discriminationfre uenc %]
time


weight [Da][min] factor MCD FSGS +
MGN


863,4 28,8 -0,45 13 57


879,6 26,9 0,58 94 36


909,4 40,3 -0,42 44 86


928,4 49,4 0,46 81 36


935,6 36,6 0,41 63 21


946,5 46,8 0,44 69 25


952,5 ~ 32 -0 41 38 79




CA 02473814 2004-07-13
-29-
1005,5 35 -0,43 25 68


1008,5 34,4 0,5 75 25


1015,6 38,2 -0,63 13 _
75


1022,5 39,1 -0,44 31 75


1028,6 37,8 0,4 69 29


1073,6 34,7 -0,49 44 93


1085,6 50,8 0,48 63 14


1138,6 22,9 0,43 50 7


1147,6 49,7 0,41 63 21


1152,5 40,7 -0,53 19 71


1199,6 31 0,41 63 21


1208,6 38,6 -0,42 19 61


1211,6 31,3 -0,45 38 82


1224,7 33,6 0,54 94 39


1270,6 25,7 -0,46 19 64


1279_,_7 38,3 -0,51 31 82


1341,8 33,1 -0,43 25 68


1381,1 32,3 -0,54 31 86


1404,9 29,4 -0,55 38 93


1433 33,7 -0,46 19 64


1487,7 41,4 0,48 88 39


1543,8 34,9 -0,44 31 75


1560,5 39,5 -0,41 38 79


1569,8 48,3 0,43 50 7


1574,8 33,9 -0,47 31 79


160_2_,8 58,1 0,41 63 21


1605,9 23,7 -0,52 13 64


__1607,7 41 -0,42 19 61


1623,3 41,4 -0,44 31 75


_1726 36,3 -0,42 44 86


1729,2 26 -0,42 44 86


1744,1 34,3 -0,52 38 89


1786,9 35,9 -0,4 31 71


1826,9 50,8 0;54 69 14


1876,2 40,1 -0,41 38 79


1880,3 57,4 0;48 63 14


1887,8 33,8 -0,46 50 96


1898,7 26,5 -0,44 31 75


1924,2 32,9 -0,54 25 79


1933,9 32,8 0,41 63 21


1950,9 34,5 -0,58 31 89


2005,3 39,6 -0,45 38 82


2033,5 27,5 -0,46 25 71


2035,6 30,9 -0,48 13 61


2065,3 20,9 -0,43 25 68


2077,3 35,8 0,47 69 _
21


2140,1 26,8 -0,41 38 79


2_15_2,7 29,5 -0,42 44 __
$6


2163,4 27,6 -0,49 19 68


2174,4 24,6 -0,48 38 86


2189,1 40,9 -0,42 19 _
61


2258,9 33,6 -0,68 25 93


2288,8 41.,4 -0,55 13 68


2332,4 35,4 -0,45 13 57


2367,7 43,2 0,5 75 25


2493,6 24,6 -0,43 50 93


2500,3 30,4 0,43 75 32


2527,3 40,8 -0,42 19 61


2614,1 ~ 22,5 ~ -0 44 31 __
~ 75




CA 02473814 2004-07-13
-30-
2660,8 27,1 _ -0,44 31 75


2665,3 39,4 -0,4 _ _
31 71


2784,3 45,2 -0,46 19 __
~ 64


2825,4 36,5 0,45 88 43


2830,9 33,2 -0,48 38 86


2864,7 29,1 0,51 69 18


2883,6 28,9 -0,43 25 68


2889,2 20,2 -0,42 19 61


2918 42,2 0,45 88 43


2921,4 30,4 0,47 69 21


_3205,8 28,3 0,43 75 32


3209,2 34,3 0,49 81 32


3255,8 42,9 0,41 63 21


3308,6 21,3 -0,4 31 71


3402,4 33,8 0,4 94 54


3578,2 32,5 -0,46 19 64


3583,3 25,2 0,43 50 7


4527,7 26 -0,46 19 64


4827,1 27,3 -0,43 25 68


7885,4 20,9 -0,45 13 57


8341,2 16,6 -0,45 38 82


9465,1 23,3 -0,45 13 57


Table 9:
molecular Migration discriminationfreauencv
weight time f%1


fDal fminl factor MGN control


803.4 35.2 0.4 56 16


814.5 28.8 0.59 83 24


815.5 30.9 -0.45 17 62


819,5 35.7 0,63 67 3


830.5 25.3 0.49 61 12


836.5 35 0.73 89 16


844.5 30.9 0.61 61 0


847.5 35.9 0.44 61 17


862.4 48.7 0.55 67 12


863.4 28.8 0.67 67 0


864.5 37.3 0.65 67 2


866.4 37,9 0.79 94 16


870.4 33.9 0.49 56 7


$73.5 38.3 0.45 50 5


874.4 49.7 0.58 61 3


874.5 29.7 0,6 89 29


879:6 26.9 -0.74 22 97


881.5 25.7 0.48 78 29


903.4 46.8 -0.44 11 55


907.4 27.5 0.47 50 3


_
909.4 40.3 0.97 100 3


925.4 50.7 0.7 83 14


926.5 36.1 -0.48 28 76


928.4 49.4 -0.57 28 84


929.5 39.9 -0.46 33 79


934.5 33.9 0.52 72 21




CA 02473814 2004-07-13
-31 -
937.5 41.7 0.48 100 52


943.5 30 0.61 89 28


946,5 46.8 -0.62 22 84


950.5 36 0.61 67 5


952.5 32 0.71 83 12


956.4 49.5 -0,6 0 60


968.6 30.5 0.43 56 12


978.5 35 0.7 72 2


978.5 23.9 0.48 50 2


980,6 34.6 -0,43 44 88


981.6 37.4 -0.41 56 97


982.5 31.9 0.56 67 10


983.5 35.1 0.58 72 14


986.5 30.3 0.54 61 7


987,4 45.1 0.54 56 2


988.5 33.9 0.49 56 7


988.6 4_9,9 -0.57 0 57


990.6 32 0.42 61 19


991.4 37.7 0.47 61 14


994.5 33.3 0.7 94 24


995.6 __36.4 0.61 83 22


998.5 35.8 0.42 56 14


1000.5 34 -0.67 28 95


1005.5 35 0.51 67 16


1006,4 35.7 -0.5 28 78


1008.5 34.4 -0,71 22 93


1010.6 50.8 -0,58 6 64


1010.6 30.6 -0,66 17 83


1013.4 39.3 -0.52 0 52


1015.6 38.2 0.78 83 5


1017.4 36.6 0.63 83 21


1022.5 39.1 0.61 83 22


1028.6 37.8 -0.76 22 98


1033.6 39.1 0.75 83 9


1038.6 34,4 0.58 72 14


1046.6 38.6 -0.91 6 97


1047.6 30.4 -0.46 39 84


1049.5 39.9 0.56 61 5


1051.5 36.2 -0.47 17 64


1055.6 36.4 0.41 50 9


1058.6 21.5 0.56 56 0


1060.6 32 0.55 94 40


1071.5 38.7 0.54 56 2


1073.6 34.7 0.84 100 16


1075.6 29 -0.47 17 64


1081.7 29.6 -0.41 11 52


1090.5 36.2 0.56 83 28


1106,5 37.2 0.44 89 45


1108.6 29.8 0.55 94 40


1109.6 34.9 -0.54 11 66


1110.4 46.9 -0.6 11 71





CA 02473814 2004-07-13
-32-
1114.5 3_7.4 _ -0.48 6 53


1121.6 42.3 -0.51 11 62


1122.5 50.2 -0.43 22 66


1131.7 34.9 0.41 67 26


1132.6 36.7 -0.45 44 90


1134.7 16.9 0.48 50 2


1135.6 42.7 -0.66 0 66


1136.6 31.6 0.43 56 12


1139.6 32.2 0.54 61 7


1141.6 38 -0.62 6 67


1150.6 35.8 0.46 94 48


1152.5 40.7 0.7 83 14


1157.6 28.5 0.6 89 29


1159.6 39 -0.75 6 81


1163.7 38.1 0.58 61 3


1171.6 32.8 0.59 61 2


1181.6 37.8 0.48 89 41


1186.6 32 0.51 83 33


1191.6 50.5 -0.41 50 91


1191.8 18.3 0.67 78 10


1198.8 29.2 0.63 94 31


1199.3 49.9 -0.46 6 52


1203.7 24.7 -0.57 0 57


1211.6 31.3 0.68 83 16


1212.7 30.6_ 0.75 83 9


1219.6 37.3 0.63 83 21


1220.6 30.2 0.51 83 33


1223.5 51.6 -0.67 22 90


1224.7 33.6 -0.67 33 100


1225.7 41.3 0.61 67 5


1226.7 41.6 0.47 50 3


1235.6 41.4 -0.5 50 100


1236.7 34.8 0.41 67 26


1237.7 41.6 -0.56 11 67


1246.7 30.5 -0.54 11 66


1254.8 52.4 -0.44 33 78


1264.6 45.9 0.52 61 9


1268.6 53.7 -0.46 6 52


1269.7 39.8 0.42 61 19


1270.5 52.5 -0.5 6 55


1270.6 25.7 0.61 67 5


1273.8 24.6 0,54 61 7


1274.6 38 0.42 56 14


1277,6 50 -0.45 17 62


1279.7 38.3 0.79 94 16


1280.6 51.9 -0.57 6 62


1283.9 28.9 0.61 67 5


1286 30.7 0.57 100 43


1292.5 53 -0.64 22 86


1297.6 38.7 0.53 94 41


1302,7 31.8 0.51 83 33





CA 02473814 2004-07-13
-33-
1308.6 53.6 -0.4 44 84


1311.8 31.5 0.75 94 19


1319.9 34.8 0.64 83 19


1321.9 41.1 -0.5 50 100


1324.2 40.5 0.52 61 9


1325.5 35.2 0.57 83 26


1331.7 35.4 -0.48 11 59


1333.8 38.8 0.77 94 17


1335.4 53.4 -0.52 0 52


1335,7 39.2 0.72 94 22


1338.7 47.2 0.76 78 2


1341.8 33.1 0.68 83 16


1350.7 50.3 -0.5 0 50


1350,8 26.8 0.46 61 16


1353.7 39.3 -0.51 39 90


1354.8 45,6 0.51 89 38


1355.7 36.3 0.4 56 16


1367.7 26.2 0.41 50 9


1370,8 33 0.41 50 9


1371.7 39.9 0.74 78 3


1371.8 19.3 0,74 100 26


1374.8 42.1 0.43 56 12


1377.7 25,4 0.52 56 3


1378.5 45.4 -0.41 56 97


1381.1 32.3 0.58 94 36


1386 24.4 0.47 56 9


1389.8 19.5 0.54 89 34


1390.7 41.1 0.42 61 19


1395.5 25.4 0.43 50 7


1397,8 36.1 0.45 56 10


1398.9 30.5 0.81 94 14


1401.8 46.2 -0.51 11 62


1404.9 29.4 0.53 100 47


1405.9 17,3 0.62 72 10


1408.9 26.8 0.56 67 10


1414.6 38.1 0.59 83 24


1415.7 33,3 0.45 50 5


1419.8 39.7 0.6 89 2g


1423.6 22.3 0.61 67 5


1424.9 18.5 0.55 67 12


1426,8 38.7 0.58 67 9


1433 33.7 0.46 72 26


1439.6 25,4 0.41 50 9


1439.7 38.1 0.41 8g 4g


1442.8 33.3 0.63 83 21


1444.6 37.8 0.54 83 29


1448.8 30.3 0.45 78 33


1453.1 27.1 0.51 61 10


1462.7 53.6 -0.48 50 98


1465.9 28.8 0.82 89 7


1472.1 31.2 0.75 89 14





CA 02473814 2004-07-13
-34-
1474.9 16.9 0.71 83 12


1482 30.4 0.72 100 28


1482.8 36.3 0.47 83 36


1484 30.4 0.69 100 31


1487.7 41.4 -0.58 33 91


1493.5 57 0.56 56 0


1497.9 26.7 0.57 78 21


1498.7 34.9 0.7 83 14


1499.9 30.6 0.6 94 34


1501.1 29.5 ~ 0.5 56. 5


1502.8 28.8 0.41 72 31


1502.9 16.8 0.76 78 2


1504.4 30.5 0.41 72 31


1508.9 16.8 0.41 50 9


1510.1 39.5 0.48 89 41


1511.7 38.4 0,43 67 24


1518 26.8 0.46 94 48


1520.7 27,9 0,64 83 19


1522.5 26.4 0.42 61 19


1527.9 34.7 0.65 94 29


1529.7 54.1 -0.62 22 84


1535 28.3 0.6 72 12


1537.9 31.5 0,56 83 28


1539.4 28.7 0.49 89 40


1540.7 29.8 0.68 83 16


1542,5 27.2 0,49 61 12


1543.8 34.9 0.54 83 29


1548.3 31.1 0.46 89 43


1552.3 35.5 0.41 100 59


1556.8 33.7 0.71 100 29


1558.1 23.4 0.52 61 9


1567 31.9 0.59 100 41


1567.6 53,9 -0.5 6 55


1568.6 34.3 0.54 83 29


1573.8 40.4 0,5 94 45


1574.3 53.4 -0.42 11 53


1574.8 33.9 0.68 89 21


1576.4 42.5 -0.62 22 84


1578 52.5 -0.48 50 98


1582.9 27.8 0.67 78 10


1588.4 47,9 -0,61 11 72


1589.7 54.3 -0.46 39 84


1595.4 31 0.61 78 17


1596.9 34 0.78 100 22


1604.3 21.6 0.42 56 14


1604.7 38.1 0.41 72 31


1605.7 53.3 -0.46 28 74


1605.9 23.7 0.74 78 3


1607,7 41 0.49 61 12


1611.7 53.2 -0.51 33 84


1612.8 36.8 0.67 100 33





CA 02473814 2004-07-13
-35-
1613.9 36.3 -0.46 39 84


1617.9 44.8 -0.4 44 84


1619.7 53.9 -0.45 _ 62
17


1622 19.2 0.55 94 40


1629.5 32 0.42 61 19


1633.8 24.6 0.62 94 33


1635.2 27.8 0.43 78 34


1644 18.8 0.52 61 9


1652.3 28.6 0.6 10G 40


1665 27.5 0,45 50 5


1666.3 23.3 0.48 89 41


1669,9 33.4 0.57 78 21


1676 25.3 0.66 78 12


1681.6 40 0.41 72 31


1686.8 38.2 0.7 94 24


1690.8 25.5 0.63 94 31


1692.4 30.4 0.46 61 16


1695.1 23.6 0.43 56 12


1699.1 41.9 0.7 94 24


1702.9 24.5 0.42 56 14


1706.8 21,5 0.51 67 16


1711 43.3 -0.54 11 66


1713.4 24.6 0.42 61 1 g


1718.5 22.6 0.75 83 9


1723.3 26.5 0.49 67 17


1726 36.3 0.86 94 g


1729.2 26 0.75 89 14


1732 51.6 -0.44 33 78


1734.6 27.2 0,47 78 31


1739.8 35.7 0.48 89 41


1744,1 34.3 0.67 100 33


1746,2 46.2 -0.68 17 84


1747.7 50.8 -0.57 0 57


1752.9 39.9 0.44 67 22


1763 24.4 0.72 94 22


1768.9 44.7 -0,63 17 79


1770,4 45,4 0.46 94 48


1772.6 28.5 0.4 56 16


1774.6 36.5 0.61 78 17


1782.1 33 0.43 94 52


1786.9 35.9 0.55 72 17


1788.6 31 0,42 83 41


1791 25 0.58 67 9


1792 25.1 0.4 56 16


1793.6 28.3 0.67 72 5


1802.5 25.6 0.53 72 19


1804.7 34 0.45 100 55


1808.1 45.6 0.56 61 5


1810.1 31.8 0.64 83 19


1811.3 31.3 0.62 100 38


1813.4 54.7 0.42 11 53





CA 02473814 2004-07-13
-36-
1819.9 24.1 0,7 83 14


1820.1 31.8 0.46 89 43


1821.2 18.2 0,61 _ 5
67


1822.9 40.7 -0.61 22 83


1824.3 37 -0.57 22 79


1826.1 21.8 0.64 78 14


1831.9 41.5 0.41 50 9


1833.5 20.4 0.48 50 2


1837.6 38.2 0.41 72 31


1839.1 35.5 0.58 94 36


1847.8 57 -0.65 28 93


1849.6 37.2 -0.48 33 81


1851.2 31.6 0.51 89 38


1853 31.2 0,78 100 22


1853.6 46.7 0.47 50 3
T


1854.2 28.8 0.54 61 7


1856.8 56.3 -0.52 17 69


1857.1 39 0.65 94 29


1859.4 22.8 0,63 67 3


1860.3 25.9 0.4 56 16


1863.8 57.5 -0.54 39 93


1864.6 28.6 0.77 94 17


1867 31.8 0.69 100 31


1870.4 30.4 0.46 94 48


1870.5 16.1 0.45 50 5


1876.2 40.1 0.65 89 24


1878.7 49.9 -0.52 28 79


1878.9 30.2 0.41 72 31


1880.3 57.4 -0,44 11 55


1883 29.1 -0.75 6 81


1885.7 57.5 -0.67 28 95


1887,8 33.8 0.48 100 52


1889.8 46.4 -0.58 39 97


1891.6 32.3 0.72 94 22


1894.9 22 0.75 94 19


1894.9 56 -0.43 22 66


1896.8 53,3 -0,5 6 55


1898.7 26.5 0.7 83 14


1904 27.5 0.59 61 2


1913.4 30.1 0.51 61 10


1913.9 53.9 -0.4 39 79


1916.8 44.7 -0.49 17 66


1920.7 30.6 0.55 100 _
45


1924.2 32.9 0.51 89 38


1931.4 26.6 0.43 56 12


1933.9 32.8 -0.86 6 91


' 1934.2 16.1 0.87 8g 2


1936.5 46.6 -0.45 22 67


1936.7 32.8 0.71 100 29


1944.1 32.2 0.47 83 36


1944.2 47 -0.75 11 86





CA 02473814 2004-07-13
-37-
1950.9 34.5 8 31
_ 0.58 9~


1951.1 53 -0.47 _ 64
- 1 T


1966.3 25.1 0.84 94 10


1971.3 35,1 0.48 89 41


1971.5 18.9 0.61 67 5


1973.7 57.1 -0.53 6 59


1977 25.5__ 0.46 94 48


1977.4 42.9 -0.66 22 88


1982.9 32.2 0.65 89 24


1986.6 35.8 0.46 72 26


1988.9 28.8 0,61 78 17


1989.3 43.7 0.79 94 16


1990.8 47.3 -0.66 17 83


2005.3 39.6 0.52 83 31


2011,3 29 0.47 56 9


2011.5 42 0.43 72 29


2013.8 45.3 -0.51 17 67


2022.6 34.6 0.55 78 22


2025 24.2 0.58 67 9


2028.4 29.9 0.7 94 24


2030.4 31.7 -0.64 17 81


2030.8 46.5 -0.64 22 86


2032.1 30.6 0.42 56 14


2033.5 27.5 0.69 78 9


2035.6 30.9 0.41 67 26


2042 26,4 0.52 100 48


2042.5 40.7 0.63 83 21


2045.9 25.3 0.53 94 41


2x47 45.4 -0.48 50 98


2050.8 38.2 0.54 89 34


2052.5 38.7 0.41 67 26


2057.2 36.3 0.43 100 57


2065.3 20.9 0,69 72 3


2079.7 21.8 0.54 61 7


2092 26.7 0.75 89 14


2092.5 41,3 0.62 78 16


2093.1 25.3_ 0.47 56 9


2095.3 33.7 0.46 89 43


2099.2 36.9 0.69 94 26


2103.6 26.7 ~ 0.51 94 43


2105.4 32.5 0.64 78 14


2109.3 27.9 0.74 94 21


2116.3 20,3 0.51 67 16


2117.1 57.1 -0.66 11 78


2121,1 43.1 0.4 61 21


2127.2 39.6 0.48 78 29


2129.5 35.1 -0.8 17 97


2140.1 26,8 0,77 89 12


2144.3 22 0.67 94 28


2146.3 25.8 0.97 100 3


2152.7 29.5 0.75 94 19


L.. I I




CA 02473814 2004-07-13
-38-
2163.4 27.6 0.56 67 10


2167.3 27.8 0,45 72 28


2172.5 36.7 0.46 94 48


2174:4 24.6 0.66 89 22


2178.5 21.4 0.69 78 9


2182.5 27.6 0.65 . 89 24


2197.9 29 0.48 67 19


2200.2 33,6 0.47 78 31


2205.6 23 0.42 56 14


2207.2 41.9 0.46 67 21


2210.7 25.7 0.72 94 22


2212.9 46.3 -0.46 39 84


2217.7 41.9 0.6 94 34


2221.1 40.7 -0.64 0 64


2223.5 22.6 0.75 83 9


2228.1 25.9 0.55 94 40


2230.1 22.8 0.52 56 3


2241 41.1 0.47 78 31


2241.1 22.7 0.63 94 31


2246.6 39,1 0,41 94 53


2253.1 22.4 0.54 56 2


2258.8 33.6 0.51 89 38


2264.4 34.8 -0.44 17 60


2266 18.5 0,5 50 0


2273.5 22.4 0.42 56 14


2279.1 47,2 -0.5 44 95


2279.5 34.8 0.46 94 48


2288.8 41.4 0.45 78 33


2288.9 27 0.48 67 19


2290.7 36.2 0.61 67 5


2291.1 21.9 0.67 72 5


2302.9 36.7 0.52 100 48


2308.9 26.2 0.63 83 21


2312.5 22.9 0.71 83 12


2322.5 47.1 0.61 67 5


2325.5 19.5 0.5 50 0


2334.2 41.2 0.45 50 5


2352.4 24.7 0.42 61 19


2356.3 24 0,68 83 16


2364.4 38.9 0,65 89 24


2367.7 43.2 -0.66 17 83


2370.7 27.3 0.49 61 12


2380 39.6 0.62 94 33


2383.9 21,1 0.52 56 3


2389.2 34.4 0.41 8g 4g


2391.2 24.3 0.82 94 12


2396.5 34.6 0.49 61 12


2406.4 31.8 0.59 100 41


2409.1 41.9 0.48 89 41


2414,5 40.8 0.4 61 21


2421 28.7 0.65 94 29





CA 02473814 2004-07-13
-39-
2426.5 38,5 0.63 9 31
4


2427.4 24 0.63 _ 31
94


2429.9 39.3 -0.48 28 76


2432.2 38.3 0.7 83 14


2435 21.6 0.54 _ 2
56


2443.4 31.9 -0.46 39 84


2446.2 24.7 0,44 61 17


2449.3 28.3 0.45 83 38


2451.7 35.5 0.44 83 40


2453.6 32 0.7 83 14


2453.8 20.4 0.56 56 0


2455.6 27.7 0.5 72 22


2461.1 40.5 0.58 _ 14
72


2464 47.2 -0.62 0 62


2465 22.8 0.89 94 5


2469,3 32.5 0.49 61 12


2471.7 23.8 0.53 72 19


2473.4 41,9 0.52 61 9


2475.5 22.3 0.49 61 12


2480.2 47.2 -0.5 22 72


2483.8 19.6 0.55 72 17


2485.9 47.5 0.41 72 31


2490.7 26.7 0.56 83 28


2493.4 46 -0.48 33 81


2493,6 24.6 0.86 100 14


2500.3 30.4 -0.57 22 79


2502.9 33 0.46 61 16


2507.3 17.2 0.48 50 2


2518.7 38.9 0.59 83 24


2521.3 48.3 0.56 61 5


2522.9 24.4 0.63 83 21


2525.5 35.6 -0.64 22 86


2527.3 40.8 0.6 72 12


2529.2 41.4 -0.49 11 60


2535 37,7 0.55 94 40


2536.6 24.8 0.47 56 9


2540.5 25.5 0.79 89 10


2548.2 35.1 -0.55 28 83


2553.7 24.7 0.44 61 17


2561.3 21.6 0.48 50 2


2566.4 22.2 0.65 72 7


2568.9 26.9 0,48 78 29


2570.5 57.1 -0:44 33 78


2573,7 16.3 0.8 gg g


2576,2 25.4 0.46 67 21


2579.5 15.2 0.63 67 3


2584 43.8 -0.69 28 97


2592.5 56.6 -0.45 17 62


2593.4 25 0.4 56 16


2601.6 23.2 0.45 56 10


2607 47.6 -0.52 22 74





CA 02473814 2004-07-13
-40-
2614.1 22.5 0.61 78 17


2619.6 38.3 0.4 61 21


2619.7 22.9 0,63 67 3


2621.4 25.8 0.66 78 12


2627.4 44,8 -0.41 50 91


2630.6 41.7 0.53 72 19


2639.6 45.2 0.5 56 5


2642.4 40.9 -0.61 17 78


2644.1 32.5 -0.6 33 93


2646.7 21.9 0.43 50 7


2654.3 37.2 -0,54 11 66


2658.5 24.7 -0.42 44 86


2660.8 27.1 0.59 78 19


2665.3 39.4 0.79 89 10


2666 23 0.45 56 10


2677.6 23.6 0.84 94 10


2687,9 28.2 0.5 56 5


2697.3 42.4 -0.48 6 53


2698.4 32.1 -0.52 28 79


2706.7 18.5 0,48 50 2


2707.2 34.1 0.45 72 28


2712.9 22.6 0.52 72 21


2713.2 41.3 -0.57 6 62


2719.9 20,2 0.67 72 5


2733.4 34.6 -0.42 44 86


2752.8 25,3 0.69 94 26


2758.5 40.9 -0.43 _ 71
28


2775.5 26.3 0.43 50 7


2780.4 28.3 0,7 83 14


2784.3 45.2 0.61 78 17


2790.3 26.8 0.62 78 16


2793.7 36.3 0.62 78 16


2809.1 37.2 -0.61 17 78


2812.5 32.8 0.62 78 16


2823.3 39,9 -0.43 44 88


2825.4 36.5 -0.59 39 98


2830,9 33.2 0.75 94 19


2834.1 38.2 -0.45 28 72


2841.6 37.1 -0.45 28 72


2848,8 36.3 -0.5 44 95


2854.4 43.8 -0.41 56 97


2875.1 59.1 0.5 50 0


2883,6 28.9 0.44 61 17


2898.5 42.3 -0.4 44 84


2902.9 42.1 0.55 67 12


2908.2 49.2 -0.42 _ 64
22


2912.9 57.5 0.5 50 0


2937.1 26.6 0.52 61 9


2945.1 22.6 0.52 61 9


2972.2 25.6 0.48 67 19


2973.7 34.9 -0.66 22 88





CA 02473814 2004-07-13
- 4~ -
2978.3 41.7 -0.52 28 79


2990.4 33_.6 -0.51 1 T 67


3007.5 30.5 -0.45 22 67


3041.2 45 -0.61 39~ 100


3044.8 48.6 -0.52 22 74


3057.1 56.4 -0.51 33 84


3058.8 35.5 -0.42 44 86


3061.9 30,4 0.54 89 34


3077 28.4 -0.55 28 83


3082:3 43.1 -0.46 33 79


3098.8 42.6 -0.44 56 100


3114.9 44.5 -0.53 33 86


3121.4 42.5 -0.56 44 100


3133.8 43.9 -0.45 17 62


3139.4 43,7 -0.61 17 78


3149.7 41.6 -0.48 50 98


3152.6 38.2 -0.61 39 100


3169 37,5 -0.41 33 74


3177.4 22.3 -0.5 22 72


3187.7 48.6 -0.53 28 81


3190.9 28.8 -0.42 22 64


3193.1 35.5 -0.46 6 52


3205.8 28.3 -0,64 22 86


3209.2 34.3 -0.63 33 97


3219.5 20.2 0.7 83 14


3232.5 35.7 -0.46 11 57


3255.8 42.9 -0.62 22 84


3256.3 23.1 0.65 67 2


3258.6 36.3 -0.52 17 69


3260.9 57.3 -0.48 6 53


3262 31.5 -0.58 28 86


3281 36,8 -0,76 22 98


3290.9 36.9 -0.6 33 93


3293.2 54.2 -0,47 50 97


3295.8 38.4 -0.65 33 98


3300.3 44.5 0,41 50 9


3303.2 38.6 -0.79 6 84


3308.6 21.3 0.74 78 3


3309.7 43.6 -0.56 17 72


3319.3 46.2 -0.56 39 95


3320 26.7 0.42 56 ' 14


3333.4 23.3 -0.55 33 88


3334.6 41.7 -0.64 22 86


3336.8 53.8 -0.58 6 64


3337.4 36.2 -0.49 39 88


3343.8 43.8 -0.41 50 91


3372.2 32.5 0.51 83 33


3381.9 43.9 -0.42 11 53


3398.9 44.5 -0.41 50 91


3402.4 33.8 -0.43 56 98


3405.7 37.8 -0.82 17 98


~




CA 02473814 2004-07-13
-42-
3433.3 44.5 56 gg
-0.43


3436 26.4 17 71
-0.54


3442.8 42.5 -0.44 56 100


3451,5 32,6 -0.43 22 66


3479.3 48.5 -0.83 _ 100
17


3503.3 23.2 -0.48 11 59


3530.9 36.8 -0,59 22 81


3552 38.8 -0.48 6 53


3578.2 32.5 0.58 72 14


3583.3 25.2 -0.79 11 90


3589.5 39.1 -0,62 28 90


3617.4 44.8 -0,53 6 59


3631.2 33.1 -0.6 11 71


3634.9 42.6 -0,52 28 79


3669.7 36.7 -0.47 17 64


3682.4 42.8 -0.57 17 74


3686.1 32.6 -0.72 11 83


3697.4 38.8 -0.42 11 53


3701.8 43.4 -0.72 0 72


3707 31.9 -0.7 6 76


3719.6 44.7 -0.55 28 83


3723.3 32.5 -0.74 22 g7


3735.8 43.9 -0.68 11 79


3739.7 47.7 -0.44 33 78


3760.8 25.9 -0.52 17 69


3802.7 46.2 -0.51 6 57


3816.7 32.2 -0.54 11 66


3852.2 36.9 -0.59 22 81


3871,7 42,9 -0.42 22 64


3881,9 26.2 0.51 61 10


3946.9 33.1 -0.65 28 93


3955.9 23.6 0.41 50 9


3969.6 31.3 -0.75 11 86


3987 30,5 -0.52 44 97


4006.7 45.9 -0.43 22 66


4026.2 30.5 -0.48 6 53


4044.7 31.2 -0.75 11 86


4055.2 24.1 0.46 61 16


4102.1 41.9 -0,5 0 50


4154.2 23.7 0.81 94 14


4170.6 46.1 -0.46 6 52


4183.7 26.6 0.67 78 10


4241.2 24.4 0.86 100 14


4283.1 24.3 0.64 72


4290.8 41.1 -0.66 22 88


4364.4 23,9 -0.42 11 53


4369.9 27.1 0.53 94 41


4527.7 26 0.7 72 2


4565.8 25.1 0.41 50 9


4626,4 27.2 0.61 67 5


4654.8 38.8 -0.41 11 52





CA 02473814 2004-07-13
-4~-
4719.5 39.3 0.5 50' 0


4748.5 25.4 -0.61 33 95


4772.1 28.9 -0.41 11 52


4801.2 37.5 -0.71 17 88


4827.1 27.3 0.82 83 2


4863.7 39.2 -0.65 6 71


5112.9 33.1 0.5 50 0


5213.8 36.8 -0.44 6 50


5229.1 39.9 -0,41 11 52


5575.8 35.7 -0.57 6 62


5829.7 20.8 0.59 61 2


5845.8 21.8 0.5 50 0


6106.5 27 0,56 __ 0
_
56


6171.5 39.6 -0.54 39 93


6212.4 30.6 _ -0.59 0 59


6238.6 30.9 -0.43 33 76


6400.9 23.4 0.7 72 2


7190.3 26.5 0,43 50 7


7284.9 40.7 0.5 50 0


7409.9 26.2 0.6 72 12


7556.6 26.2 0.73 89 16


7572.8 25.7 0.55 67 12


7885.4 20,g 0.56 61 5


8054.8 16.7 0.75 94 19


8216.9 16.8 0.45 50 5


8341.2 16.6 0.88 94 7


8371.2 15.8 0.61 61 0


8466.3 18 0.56 61 5


8518.7 15.7 0.76 78 2


8578.4 17 0.61 67 5


8653,1 17.2 0.55 67 12


8765.9 17.6 0.67 100 33


8803.1 16.2 0.47 _ 3
50


8928.6 17 0.49 56 7


9060.7 23 0.62 72 10


9076 23 0.62 72 10


9182 17.1 0.8 8g 9


9208 22.9 0.61 67 5


9223.1 22.8 0.76 83 7


9335.5 17.5 0.69 72 3


9465.1 23.3 0,61 61 0


9480.1 23.6 0.56 56 0


9621.9 19.2 0.58 67 9


9868.8 29.5 -0.55 22 78


9933.5 18,4 0.52 56 3


9944.2 16.7 0.63 67 3


10046.3 18.1 0.81 100 19


10390.1 20.2 0.77 89 12


10518.8 20.9 0.53 72 19


10949.7 26.3 0.5 56 5




CA 02473814 2004-07-13
-44-
Table 10:
molecular migrationdiscriminationfrequency
weight time [min]factor [%]
[Da]


MGN FSGS +
MCD


814,5 28,8 0,41 83 42


819,5 35,7 0,47 67 19


863,4 28,8 0,44 67 23


864,5 37,3 0,44 67 23


879,6 26,9 -0,59 22 81


909,4 40,3 0,5 100 50


_928,4 49,4 -0,41 28 69


1015,6 38,2 0,53 83 31


1017,4 36,6 0,49 83 35


1022,5 39,1 0,41 83 42


1073,6 34,7 0,42 100 58


1152,5 40,7 0,53 83 31


1224,7 33,6 -0,44 33 77


1279,7 38,3 0,52 94 42


1283,9 28,9 0,44 67 23


1301,7 34 0,4 56 15


1319,9 34,8 0,41 83 42


1329,8 37,5 0,41 72 31


1341,8 33,1 0,53 83 31


1381,1 32,3 0,48 94 46


1404,9 29,4 0,46 100 64


1423,6 22,3 0,47 67 19


1433 33,7 0,41 72 31


1490,7 33,7 0,47 67 19


1543,8 34,9 0,41 83 42


1574,8 33,9 0,47 89 42


1595,4 31 0,43 78 35


1602,8 58,1 -0,43 11 54


1605,9 23,7 0,55 78 23


1612,8 26,3 0,4 56 15


1726 36,3 ~ 0,41 94 54


1744,1 34,3 0,5 100 50


1768,9 44,7 -0,56 17 73


1774,6 36,5 0,43 78 35


1799 28,8 0,41 72 31


1802,5 25,6 0,49 72 23


1839,1 35,5 0;41 94 54


1876,2 40,1 0,43 89 46


1883 29,1 -0,44 6 50


1885,7 57,5 -0,45 28 73


1898,7 26,5 0,41 83 42


1924,2 32,9 0,5 89 38


1933,9 32,8 -0,52 6 58


1971,5 18,9 0,47 _ 19
67


2011,3 29 0,4 56 15


2079,7 21,8 0,42 61 19


2109,3 27,9 0,44 94 50


2140,1 26,8 0,43 89 46


2152,7 29,5 0,41 94 54


2160,4 27,9 0,4 56 15


2274 37 0,42 50 8


_
2288,8 41,4 _ 0,51 ( 78 _
~ 27


2292,4 35, 0,43 78 ~ 35




CA 02473814 2004-07-13
- 45 -
2312,5 22,9 0,45 83 38


2332,4 35,4 0,44 67 23


2338,6 26 0,43 89 46


2341,2 26,3 0,44 56 12


2356,3 24 0,45 83 38


2367,7 43,2 -0,45 17 62


2380 39,6 0,44 94 50


2391,2 24,3 0,41 94 54


2421 28,7 0,41 94 54


2451,7 35,5 0,45 83 38


2453,6 32 0,53 83 31


2453,8 20,4 0,44 56 12


2461,1 40,5 0,41 72 31


2469,3 32,5 0,46 61 15


2471,7 23,8 0,41 72 31


2500,3 30,4 -0,43 22 65


2521,3 48,3 0,42 61 19


2525,5 35,6 -0,51 22 73


2527,3 40,8 0,45 72 27


2639,6 45,2 0,4 56 15


2642,4 40,9__ -0,41 17 58


2665,3 39,4 0,54 89 35


2677,6 23,6 0,44 94 50


_2784,3 45,2 0,51 78 27


2830,9 33,2 0,44 94 50


2912,9 57,5 0,42 50 8


3041,2 45 -0,42 39 81


_3_205,8 28,3 -0,43 22 65


3256;3 23,1 0,44 67 23


3313,8 31,6 0,51 78 27


3336,8 53,8 -0,44 6 50


3479,3 48,5 -0,56 17 73


3578,2 32,5 0,41 72 31


418_3,7 26,6 0,43 78 35


4527,7___26 0,41 72 31


4827,1 2_7,3 0,53 83 31


5112,9 33,1 0,42 50 8


5829,7 20,8 0,46 61 15


6106,5 27 0,48 56 8


8341,2 16,6 0,48 94 46


8371,2 15,8 0,46 61 15


8466,3 18 0,46 61 15


8518,7 15,7 0,51 78 27


8578,4 17 0,47 67 19


9182 17,1 0,43 89 46


9944,2 16,7 0;44 67 23


10949,7 26,3 0,48 56 8


Table 11:
molecularmigrationdiscriminationfrequency
[%J


weight time [min]factor IgA control
[Da] +
MGN


800,5 22,5 -0,41 14 55


866,5 22 0,52 52 0


874,7 19,2 0,45 52 7


879,5 15,6 -0,84 9 93


937,5 23 0,43 57 14




CA 02473814 2004-07-13
-46-
981,6 21,3 -0,42 34 76


995,5 21,4 0,5 54 3


1010,6 16,3 -0,57 5 62


1028,6 21,2 -0,56 13 69


1046,5 21,5 -0,74 9 83


1060,7 17,4 0,47 61 14


1134,6 20,4 -0,59 41 100


1169,5 45,7 -0,52 4 55


1194,7 22,9 -0,68 32 100


1219,7 23,7 0,43 61 17


1224,7 18,1 -0,58 11 69


1235,3 23,2 -0,59 27 86


1250,6 23 -0,52 48 100


1265,6 23 -0,77 23 100


1285,8 18 0,54 57 3


1297,6 22,1 0,61 75 14


1321,7 23,6 -0,46 20 66


1333,7 22,8 0,54 54 0


1335,5 21,1 0,45 63 17


1368,8 17 0,65 75 10


1386,9 17,2 0,75 79 3


1404,8 16 0,61 75 14


1424,4 32,1 -0,57 43 100


1438,5 23,6 -0,43 54 97


1448,6 17,5 0,57 64 7


1460,9 19,5 0,54 54 0


1482 17,7 0,65 71 7


1493,8 20 0,48 52 3


1499,9 17,6 0,77 88 10


1539,7 34,1 -0,72 25 97


1567 19,2 0,59 63 3


1579,5 22,9 -0,56 30 86


1585 18,1 0,77 91 14


1621,8 13,4 0,47 75 28


1644,4 20,8 0,63 63 0


1651,9 17,2 0,64 68 3


1698,1 18,4 0,72 96 24


1760 17,7 0,5 57 7


1805,1 19,8 0,5 50 0


1811,2 17,9 0,83 96 14


_1819,7 20,4 0,52 59 7


1829,1 18 0;5 98 48


1851,1 17,8 0,77 84 7


1863,8 37 -0,52 38 90


1867,2 18,6 0,82 86 3


1872,9 18,6 ~ 0,65 71 7


1878,5 17,3 0,52 59 7


1_880,1 37,5 -0,48 7 55


1895,1 16,2 0,63 77 14


1924,5 20,4 0,52 52 0


1943 19,5 0,79 86 7


1955 19,9 0,41 52 10


1977 12,7 -0,57 5 62


_2039,1 18,6 -0,49 27 76


2_042,1 17,7 0,68 75 7


2048 19,9 -0,54 46 100


2057,3 19,1 0,71 71 0


2133,3 21,5 0,5 64 14


2147 19,5 0,54 68 14




CA 02473814 2004-07-13
-47-
2174,9 27,8 -0,81 9 90


2233,1 18,1 -0,48 11 59


2246,2 22,1 0,68 68 0


2249,1 18,7 -0,42 23 66


2258,6 18,9 0,5 50 0


2279,5 22,5 0,5 54 3


2377,4 18,4 -0,67 13 79


2389,2 18,6 0,59 66 7


2405,6 17,8 0;59 59 0


2427,1 16,4 0,84 95 10


2502,2 19,2 0,5 61 10


2518,7 18,8 0,61 64 3


2540,4 16 0,68 75 7


2562,9 19,1 -0,52 38 90


2566,7 13,9 0,66 70 3


2608,3 21,8 0,54 75 21


2621,5 16,5 0,68 71 3


2649,6 28,9 -0,5 13 62


2695,4 19,7 -0,54 43 97


2742,3 23,7 -0,61 36 97


2752,4 15,5 0,83 93 10


2755,3 23,6 0,68 71 3


2790,6 16,4 0,64 64 0


2799,7 20,4 -0,45 48 93


2825 20,8 -0,63 38 100


2838,7 20,3 -0,57 36 93


2914,8 17 0,43 50 7


2936,8 16 0,7 70 0


3011,5 24,5 -0,68 32 100


3013,3 16,8 -0,42 20 62


3040,9 25,5 -0,72 25 97


3098,3 24,8 -0,51 11 62


3205,9 15,7 -0;53 9 62


3209,4 19 -0,67 16 83


3265,5 24 -0,66 23 90


3281,1 27,3 -0,56 38 93


3287,4 25,2 -0,54 39 93


3303,5 28,7 -0,49 23 72


3333,2 14,1 -0,64 5 69


3359,6 26,2 -0,72 4 76


3375,6 25,3 -0,5 9 59


3385,7 21,2 -0,61 32 93


3402,3 17,8 -0,56 13 69


3405,3 21,6 -0,75 18 93


3416,7 26,4 -0,46 9 55


3432,5 25,6 -0,69 7 76


3441,6 25,4 -0,45 55 100


3457,8 25,4 -0,45 55 100


3_502,8 14,8 -0,48 7 55


3582,9 14,2 -0,72 7 79


3969,1 18,1 -0,43 13 55


3987,1 17,3 -0,63 27 90


4044,5 18 -0,44 14 59


4054,8 15,5 0,45 59 14


4098,2 20,5 -0;56 23 79


4153,7 14,7 0,58 71 14


4240,6 14,8 0,63 84 21


4290,3 23,4 -0,65 7 72


4306,5 23,5 -0,57 2 59




CA 02473814 2004-07-13
- 48 -
4369,2 15,5 0,44 75 31


4626 15,7 0,52 55 3


4712,9 15,8 0,72 79 _
7


4748 14,7 -0,67 20 86


6171,4 23 -0,7 16 86


6186,7 23,3 -0,67 20 86


8764,7 12,8 0,46 88 41


9868,4 17,2 -0,63 9 72


1_0044,3 13,1 0,65 89 24


10516,9 13,9 _ _
0,45 52


12719 22,6 -0,44 25 69


Table 12:
molecularmigration discriminationfrequency
weight time factor [%)
[Da) [min) IgA
control


800,5 22,5 -0,44 12 55


852,6 19,7 0,51 51 0


862,4 27,2 0,56 56 0


866,5 22 0,58 58 0


879,5 15,6 -0,91 2 93


937,5 23 0,49 63 14


981,6 21,3 -0,48 28 76


995,5 21,4 0,55 58 3


1008,5 20 -0,44 12 55


1010,6 16,3 -0,6 2 62


1028,6 21,2 -0,57 12 69


1033,7 21,6 0,53 53 0


1046,5 21,5 -0,8 2 83


1134,6 20,4 -0,63 37 100


1144,7 25,8 0,48 51 3


1169,5 45,7 -0,51 5 55


1181,6 23,7 0,48 65 17


1194,7 22,9 -0,65 35 100


1219,7 23,7 0,55 72 17


1224_,7 18,1 -0,64 5 69


1235,3 23,2 -0,61 26 86


1250,6_ 23 -0,49 51 100


1265,6_ 23 -0,79 21 100


1297,6 22,1 0,63 77 14


1321,7 23,6 -0,52 14 66


1333,7 22,8 0,63 63 0


1335,5 21,1 0,55 72 17


1368,8 17 0,64 74 10


1386,9 17,2 0,71 74 3


1404,8_ 16 0,58 72 14


1424,4 32,1 -0,49 51 100


1448,6 17,5 0,54 60 7


1482 17,7 0,61 67 7


1493,8 20 0,55 58 3


1499,9 17,6 0,76 86 10


1539,7 34,1 -0,66 30 97


1567 19,2 0,5 53 3


1573,8 27,8 0,49 7T 28


1579,5 22,9 -0,65 21 86


1585 18,1 0;79 93 14


1621,8 13,4 0,47 74 28


1644,4 20,8 0,63 63 0


1651,9 17,2 0,62 65 3




CA 02473814 2004-07-13
-49-
1689,7 32,2 0,47 53 7


1698,1 18,4 _ 0,74 98 24


1811,2 17,9 0,84 98 14


1819,7 20,4 0,47 53 7


1829,1 18 0,49 98 48


1851,1 17,8 0,74 81 7


1863,8 37 -0,43 47 90


186_7,2 18,6 0,8 84 3


1872,9 18,6 0,63 70 7


1878,5__17,3 0,49 56 7


1880_,1_37,5 -0,48 7 55


1895,1 _16,2 0,58 72 14


__1924,520,4 0,51 51 0


1943 _19,5 _ 0,79 86 7


1955 19,9 0,43 53 10


1977 12,7 -0,57 5 62


2039,1 18,6 -0,53 23 76


2042,1 17,7 0,7 77 7


2048 19,9 -0,6 40 100


2057,3 19,1 0,67 67 0


2133,3 21,5 0,56 70 14


2147 19,5 0,44 58 14


2174,9 27,8 -0,8 9 90


2233_,1_18,1 -0,52 7 59


2246,2 22,1 0,79 79 0


2249,1 18,7 -0,49 16 66


2279,5 22,5 0,5 53 3


2377,4 18,4 -0,79 0 79


2389,2 18,6 0,63 70 7


2405,6 17,8 0,58 58 0


2427,1 16,4 0,83 93 10


2483,4 21,6 -0,47 12 59


2502,2 19,2 0,57 67 10


2518,7 18,8 0,52 56 3


2540,4 16 0,68 74 7


2562,9 19,1 -0,52 37 90


2566,7 13,9 0,71 74 3


2608,3 21,8 0,65 86 21


2621,5 16,5 0,69 72 3


2649,6 28,9 -0,5 12 62


2695,4 19,7 -0,59 37 97


2742,3 23,7 -0,62 35 97


2752,4_ 15,5 0,85 95 10


2755,3 23,6 0,8 84 3


2761,3 17,7 -0,4 12 52


2790,6 16,4 0,6 60 0


2799,7 20,4 -0,42 51 93


2825 20,8 -0,67 33 100


2838,7 20,3 -0,58 35 93


2936,8 16 0,67 67 0


3011,5 24,5 -0,63 37 100


3013,3 16,8 -0,48 14 62


3040,9 25,5 -0,69 28 97


3098,3 24,8 -0,57 5 62


3205,9 15,7 -0,57 5 62


3209,4 19 -0,73 9 83


3265,5 24 -0,69 21 90


32_81,1 27,3 -0,56 37 93


3287,4 25,2 -0,47 47 93


3303,5 28,7 -0,49 23 72


3333,2 14,1 -0,67 2 69




CA 02473814 2004-07-13
-5~-
3359,6 26,2_ -0;71 5 76


3375,6 25,3 -0,54 5 59


3385,7 21,2 -0,56 37 _
93


3402,3 17,8 -0,57 12 69


3405,3 21,6 -0,79 14 93


3416,7 26,4 -0,44 12 55


3432,5 25,6 -0,67 9 76


3502,8 14,8 -0,53 2 55


3582,9 14,2 -0,72 7 79


3841,4 14,9 -0,44 42 86


3969,1 18,1 _ 14 55
-0,41


3987,1 17,3 -0,62 28 90


4044,5 18 -0,42 16 59


4098,2 20,5 -0,51 28 79


4153,7 14,7 0,51 65 14


4240,6 14,8 0,61 81 21


4290,3 23,4 -0,63 9 72 .


4306,5 23,5 -0,56 2 59


4712,9 15,8 0,68 74 7


4748 14,7 -0,68 19 86


6171,4 23 -0,68 19 86


6186,7 23,3 -0,65 21 86


8764,7 12,8 0,45 86 41


9868,4 17,2 -0,63 9 72


10044,3 13,1 0,64 88 24


Table 13:
molecularmigration discriminationfrequenc
weight time factor IgA
[Da] [min] MGN


816,7 16 -0,47 7 54


852,6 19,7 0,51 51 0


862,4 27,2 0,56 56 0


874,7 19,2 -0,43 42 85


943,6 17,5 -0,59 26 85


977,6 18 -0,5 12 62


994,5 18,3 -0,52 2 54


1004,6 22,4 -0,49 5 54


1040,4 19,5 -0,59 2 62


1060,7 17,4 -0,41 51 92


1099,8 17,5 -0,57 28 85


1108,6 17,3 -0,5 42 92


1143,6 30,2 0,45 60 15


1157,5 31,6 0,47 63 15


1179,6 31,6 0,49 72 23


1186,7 19,7 -0,49 5 54


1195,6 31,4 0,64 79 15


1198,8 17,7 -0,49 28 77


1203,7 19,3 0,45 60 15


1217,6 30,1 0,78 93 15


1219,7 23,7 0,49 72 23


1239,6 30,6 0,75 91 15


1252,7 20,5 -0,81 12 92


1255,6 29,4 0,49 72 23


1261,5 30,1 0,51 74 23


_1268,4 23 -0,51 26 77


1270,7 16,6 -0,47 7 54


1285,8 18 -0,46 47 92


1287,6 18,8 ~ -0,55 14 69




CA 02473814 2004-07-13
-51 -
1311,8 17,9 -0,46 23 69


1335,5 21,1 0,41 72 31


13_40,6 16,7 -0,52 9 62


1343,1 18,5 -0,48 21 69


1350,8 19 -0,48 14 62


1365,7 21,2 -0,62 7 69


1377,8 17,1 -0,4_7 7 54
- _. _
-


- 19'8 _O 7 69
X381 62


1402,4 18,7 -0,52 2 54


1405,8 31,3 0,54 70 15


1424,8 14,7 -0,5 12 62


1446,7 32,7 0,44 67 23


1455,8 20,7 -0,7 7 77


1464,1 21,3 -0,55 7 62


1465,7 _19_,_4 -0,67 2 69
_


147_0_,8 17,3 -0,47 7 54


1472 21,3 -0,53 16 69


1484,5 17,5 -0,73 12 85


1486,4 19,5 -0,58 12 69


1514,6 19,4 -0,49 5 54


1519,1 13,4 -0,5 12 62


1523,7 33 0,65 95 31


1539,6 21,8 -0,62 30 92


1545,8 33,5 0,61 84 23


1556,7 19,6 -0,85 0 85


1561,8 33,3 0,55 93 38


1561,9 19,8 -0,57 5 62


1573,8 27,8 0,61 77 15


1579,5 22,9 -0,41 21 62


1596,9 18,3 -0,6 9 69


1603 19,1 -0,55 7 62


1611,6 32,9 0,51 51 0


1627,6 19,6 -0,52 2 54


1637,8 19,3 -0,6 9 69


1651,8 34 0,59 74 15


__1707,6 19,7 -0,42 12 54


1726 20,1 -0,6 9 69


1775,9 20,8 -0,42 12 54


1782,3 18,9 -0,42 35 77


1787,7 19,3 -0,48 14 62


1791,3 19,3 -0,56 21 77


1793,1 23 -0,61 16 77


1799,3 18,7 -0,54 0 54


1845,3 20,1 -0,68 9 77


1876,8 19,2 -0,52 33 85


1887,6 21,5 -0,45 9 54


1891,2 18,7 -0,59 2 62


1936,5 21,6 -0,46 23 69


1968,5 27,3 -0,5 12 62


_1971,3 22,2 -0,5 12 62


1988,9 18,9 -0,42 12 54


2014,9 18,1 -0,69 23 92


2025,9 21,7 -0,49 5 54


2063,8 17,7 -0,49 51 100


2085,9 21 -0,45 9 54


2113 18,6 -0,42 12 54


2129,1 16,6 -0,57 5 62


2135,3 18,1 -0,68 9 77


2147 19,5 -0,42 58 100


2154,1 21,2 -0,44 33 77


2159 23,1 -0,47 37 85




CA 02473814 2004-07-13
-52-
2166,6 20,1 -0,48 14 62


2171,7 21,1 -0,41 21 62


2178,4 14,9 -0,52 9 62


2183,5 16,3 -0,47 7 54


2229,5 20,2 -0,7 7 77


2246,2 22,1 0,48 79 31
2290,5 20,1 -0,41 21 62


2292,2 20,6 -0,47 7 54


2309,7 16 -0,52 2 54


2325,2 18,2 -0,53 16 69


2361,6 17,3 -0,49 5 54


2377,4 18,4 -0,54 0 54


2407,5 19,3 -0,45 9 54


2421,1 16,1 -0,62 0 62


2464,4 19,8 -0,69 23 92


2466,6 17 -0,48 21 69


2475,8 18,8 -0,64 21 85


2483,4 21,6 -0,73 12 85


2493,3 14,9 -0,57 28 85


2522,4 16,3 -0,41 28 69


2547,1 17,9 -0,55 14 69


__25 17,7 -0,72 5 77
53,7_


_ 20,3 -0,45 16 62
2573,5 -
-


2586,7 1$'5 _p,59 2 62


2599,2 21 -0,68 9 77


2608,3 21,8 0,48 86 38


2669,1 18,4 -0,52 2 54


2676 20,6 -0,55 14 69


2681,5 _20,1 -0,42 12 54


2684,2 _19_,4 _ 7 62
-0,55


2687,5 19,2 -0,59 2 62


2755,3 23,6 0,53 84 31


2807,6 17,3 -0,47 7 54


2810,5 18,1 -0,5 12 62


2_83_1,2 19 -0,43 19 62


2847,7_ 16,5 -0,5 35 85


_2914,8 17 -0,45 40 85


2959,7 16,6 -0,47 7 54


3030 16,7 -0,44 26 69


3062,1 17,9 -0,54 23 77


3441,6 25,4 0,62 70 8


3478,6 27,6 0,78 86 8


3495,5 25,8 0,71 79 8


3841,4 14,9 -0,43 42 85


4183,6 16,3 -0,45 9 54


4479,4 14,8 -0,45 9 54


4483,2 16,2 -0,47 7 54


_4527,6 16,3 -0,5 12 62


4566,6__ 16,6 -0,52 2 54


4594,4 14,2 -0,45 9 54


8053,8 12,9 -0,44 26 69


Table 14:
mass CE frequency mass CE_t frequency
t [%] [%]


[Da] [min]controlFSGS MCD MGN [Da [min]controlFSGS MCD MGN


3012,0939,45100 60 94 72 1028,57.37,7998 40 69 22


1539,6750,20100 90 100 89 876,4148,8998 70 38 67




CA 02473814 2004-07-13
-53-
2249,1933,82100 80 83 2205,0336,9498 70 88 83
100


3152,5538,22100 60 39 3402,4033,83_98 50 94 56
69


3360,0944,33100 60 72 2377,6032,0698 80 94 83
81


3001,9748,35100 100 89 2175,0344,2798 80 100 100
100


2257,1946,60100 60 67 2385,4545,4798 80 81 94
81


2563,4232,22100 90 72 2046,9945,3998 50 56 50
75


2158,9846,70100 90 89 2409,9032,5498 100 94 94
88


3287,9743,92100 90 89 3433,2844,4698 70 56 56
100


3385,7636,60100 100 72 1545,7554,7298 90 100 89
81


3271,8044,05100 80 61 2736,3132,3097 100 94 89
94


2007,6933,06100 90 89 3723,3332,4897 20 50 22
88


1194,6139,46100 70 88 83 1737,7641,2997 90 88 89


1265,6240,371_00 70 94 72 1378,5445,4597 60 81 56


1435,6939,91100 90 94 89 2854,4143,8097 50 75 56


1261,5349_,63100 80 88 61 2068,5441,069T 80 81 61


1438,5637,63100 100 100 100 2663,3636,3897 80 88 83


1446,5052,53100 80 94 67 2085,5039,2197 100 94 94


3265,7742,28100 80 75 78 2682,4935,0397 90 75 89


3121,3642,46100 50 75 44 1046,5738,6397 20 38 6


1911,1437,40100 90 100 94 2994,6140,6397 90 88 72


1321,9141,10100 70 69 50 2583;9843,7597 30 62 28


2695,4935,27100 70 88 78 2129,4835,1497 60 50 17


1235,5941,42100 60 69 50 981,56 37,3997 50 81 56


2799,9437,08100 80 88 83 879,55 26,9597 60 94 22


2169,7539,56100 100 100 94 2394,2936,3297 100 100 94


1224,7433,57100 50 94 33 3986,9830,.4697 50 69 44


1451,6741,11100 100 100 83 2483,5838,7497 90 81 78


3479,3248,53100 70 75 17 1523,7354,2997 90 1 89
00


2649,9445,91100 90 75 78 1889,7646,3 97 _ _ 39
8 30 44


2687,3641,87100 60 75 61 1507,64_ 97 90 100 89
54,43


3458,5244,64100 90 94 72 3209,2234,2797 30 81 33


3442,8442,54100 80 94 56 3022,8233,8297 40 62 61


2048,1933,07100 40 81 61 1765,1735,5097 90 88 94


2679,4634,99100 50 94 67 1367,673,27 97 90 94 94
5


2227,3438,28100 70 62 83 2726,38_ 97 100 88 _
40,38 100


1239,5250,23100 100 100 78 1179,5752,1797 80 100 83


3098,8042,63100 60 81 56 1651,8655,1597 90 100 78


2839,0735,41100 80 88 83 3376,2445,'1797 50 88 67


3417,1245,12100 70 81 61 3293,1554,2197 50 75 50


3426,2042,48100 70 88 72 1579,5039,4397 100 94 94


3041,1645,04100 80 81 39 3474,2743,3795 70 75 67


1508,7041,2698 90 94 61 2848,8336,3395 70 75 44


1462,6753,5898 70 88 50 3319,2846,2295 50 62 39


3280,9636,7698 20 50 22 1000,5233,9695 40 44 28


1877,3329,6298 100 100 100 3281,9749,4495 60 50 56


2742,2542,2598 90 75 89 1885,7457,4795 70 75 28


3092,7143,8698 90 81 78 3556,9234,8595 100 75 78


2196,6645,4598 80 100 89 1609,1742,6095 100 94 89




CA 02473814 2004-07-13
-54-
6187,5539,7898 60 94 67 2767,4131,3995 40 69 56


2825,4236,5498 __50 88 39 3108,8144,7095 50 75 56


1255,5549,8198 100 100 78 2233,0031,0695 30 69 56


2717,5634,4398 60 69 61 882,55 36,5595 60 31 72


3149,6741,6298 70 88 50 1680,1637,3295 100 94 100


1195,5351,7698 70 94 83 1673,8054,59g5 80 94 61


3496,0243,8598 90 94 61 2336,7842,4795 70 94 89


1561,6_954,1798 90 100 83 1217,6448,5495 100 94 83


1250,6341,9798 70 100 89 1489,4942,2195 90 94 72


3295,7738,3698 50 50 _33 2442,0646,8595 70 81 67


3405,6837,8498 40 62 17 2279,0647,1695 70 69 44


1578,0152,5398 70 75 50 4748,5125;3895 50 38 33


1134,5837,1198 90 94 94 1766,8435,1595 100 100 100


Table 15:
Frequency FrequencyFrequencyFrequency
Mass CE-timeHealthy FSGS MCD MGN
Da min


1435,6932,7 94 86 100 7


1282,3929,3 69 29 29 0


3531,0126,9 69 0 0 0


5801,9413,3 69 0 7 7


Table 16:
health vs, renal atients


_
mass Da _ .,_- _._- CE time min


-
909,4 40,3


1159,6 39,0


1338,7 47,2


1686,8 38,2


1847,8 57,0


1966,3 25,1


1990,8 47,3


2146,3 25,8


2432,2 38,3


2465,0 22,8


3707,0 31,g


Table 17:
MGN vs. MCD
Mass CE t
879,6 26,9


CA 02473814 2004-07-13
- SS
1279,7 38,3


1341,8 33,1


1404,9 29,4


1569,8 48,3


1574,8 33,9


1605,9 23,7


252_7,340,8


15112,933,1


Table 18:
MCD vs.
FSGS


Mass CE t


1199,6 31,0


1826,9 50,8


2077,3 35,8


2258,9 33,6


12918,0 42,2


Table I9:
MGN
vs.
FSGS


Mass CE
t


2312,5 22,9


2453,6 32,0


2639,6 45,2


9182,0 17,1


Table 20:
mass CE time mass CE
Da ~ %health% MGN Da time %health% MGN
min [min


4098,240,1 100 0 1933,0241,5 100 12


3685,935,9 100 0 1889,8249,3 100 12


3531,342,9 100 0 1636,6946,8 _ 12
100


3359,748,4 100 0 1579,7647,3 100 12


3287,447,4 100 0 1438,6645,4 100 12


3265,351,6 100 0 1321,5945,8 100 12


3098,546,9 100 0 1255,5353 100 12


3041,346,5 100 0 1200,5353,4 100 12


3011,346,5 100 0 2427,4327 12 100


2742,245,8 100 0 1829,0933,8 12 100


2563,234,5 100 0 4627,0128,7 0 88


2483,544,5 100 0 2621,4229 0 88


2385,250,4 100 0 1942,5734,8 0 gg




CA 02473814 2004-07-13
-56-
1893,1 42,5 100 0 1867,0633,8 0 88


1639,9 47,5 100 _ 0 1759,9232,5 _ 88
0


1609,7 47,3 100 0 1460,8339,8 _ 88
y 0


1580,9 41,3 100 0 3013,3636,6 88 12


1508,7 46,6 100 0 2838,9 39,8 88 12


1489,6 46,2 100 0 2710,3152,8 88 12


1424,7 56 100 0 2395,0440,4 88 12


1407,6 54,6 100 0 1876,9137,2 88 12


1160,6 52,7 100 0 1863,8659,2 88 12


981,53 41 100 0 1651,8156,5 88 12


980,54 38 100 0 1561,5656,1 88 12


876,4 52,2 100 0 1523,7256,1 88 12


2752,9 29,3 0 100 1473,6646,4 88 12


6171,1 43,4 88 0 1261,4953,2 88 12


3851,9 41,2 88 0 1195,5 54 88 12


3706,8 35,2 88 0 10047 22,3 12 88


3634,2 43,6 88 0 4713,9428,8 12 88


3631,3 36,3 88 0 4241,4126,7 12 88


3478,9 47,9 88 0 1811,1334,6 12 88


3376,3 48,5 88 0 1753,9832,7 12 88


3338,2 38,6 88 0 1698,0634,1 12 88


3292;7 56,7 88 0 1584,9132,7 12 88


3280,6 42,2 88 0 4353,6233,6 75 0


3271,5 47,3 88 0 4102,4545,2 75 0


3248,5 47,2 88 0 4044,5834,1 75 0


2849,2 39,4 88 0 3987,4834,8 75 0


2736,4 39,3 88 0 3947,2236 75 0


2682,1 37,3 88 0 3589,6541,3 75 0


2642,6 44,7 88 0 3433,1248,6 75 0


2584,3 51,9 88 0 3416,9248,6 75 0


2257,1 50,3 88 0 3295,5342 75 0


2204,9 44 88 0 3261,5535,6 75 0


2196,9 49,9 88 0 3258,5237,8 75 0


2039,2 35,8 88 0 3193,4837;3 75 0


1680,8 47 88 0 3152,6 40,3 75 0


1635,8 56,8 88 0 3092,0847,6 75 0


1539,7 46,3 88 0 2863,2540,6 75 0


1423,7 54,4 88 0 2854,5552,4 75 0


1422,5 55 88 0 2698,3737,2 75 0


1353,7 43,2 88 0 2548,4237,7 75 0


1046,6 42,6 88 0 2464,0750,8 75 0


3969,5 34,4 100 12 2406,9850,6 75 0


3496,1 47,1 100 12 2279 50,2 75 0


3442,2 47,9 100 12 2233,0235,7 75 0


3405,4 42,4 100 12 2226,9743 75 0


3385,6 41,5 100 12 2019,9741,1 75 0


3281,7 53 100 12 1991,9536,2 75 0


3209,4 37,1 100 12 1849,8541,1 75 0


~ 2799,942,4 100 12 ~ 1768 48,7 75
~ ~ I 95 ~
~




CA 02473814 2004-07-13
-57-
2378 38,8 100 -- 12 1755,0248,2 75 0
~


2170 42,6 100 12 1737,7848,2 75 0


2008 37 100 12 1462,6356,1 75 0


1949 41,5 100 12 1446,656 75 0


1425,7841,6 ~ 0
-- ~~----
75


Table 21:
mass CE
Da time %health% MGN
min


1405,6 55,7 75 0


1389,6 55,3 75 0


1322,6 45,4 75 0


1262,6 56,4 75 0


1246,6 55,6 75 0


1224,8 35,4 75 0


1141,7 41,6 75 0


1028,6 41,9 75 0


946,43 50,5 75 0


3723,1 35,5 100 25


3458,2 48,2 100 25


3001,8 51,8 100 25


2825,3 40,8 100 25


2695,3 39,1 100 25


2679,2 39,2 100 25


2410 39,6 100 25


2394 39,3 100 25


2048 35,9 100 25


1911,1 41,6 100 25


1545,7 57,3 100 25


1507,7 57,3 100 25


1467,8 41 100 25


1451,7 46,4 100 25


1435,7 46,3 100 25


1265,6 44,6 100 25


1250,6 45,7 100 25


1239,4 53,7 100 25


1235,6 44 100 25


1217,6 53,3 100 25


1194,6 44,1 100 25


1179,5 55 100 25


1716 32,1 25 100


4827,2 29,3 0 75


2937,4 29,6 0 75


2057,4 37 0 75


1851,1 33,8 0 75


1680,1 33,6 0 75


1517,9 30,2 0 75




CA 02473814 2004-07-13
-58-
1483,9 32,5 0 75


1481,9 33,8 0 . 75


1404,8 29 0 75


1398,8 34,1 0 75


1367,6 56,1 88 25


1157,6 54,9 88 25


3474,3 47,9 75 12


3402,5 37 75 12


2761,4 34,7 75 12


2644,1 33,5 75 12


2587,2 34,9 75 12


2579,7 50,5 75 12


2579,7 41,4 75 12


2175 50 75 12


2069,1 49,5 75 12


2047 49,5 75 12


1170,6 46 75 12


1386,8 32,3 25 88


8766,7 21,6 12 75


4154,4 26,4 12 75


3842,8 25,7 12 75


1873 33,9 12 75


1566,9 33,2 12 75


1499,9 33,7 12 75


1368,8 31,6 12 75


1285,7 31,1 12 75


1108,6 32,2 12 75


1099,6 31,2 12 75


1060,6 31,6 12 75


Table 22:
healthy, disease,
time mass Da fre uenc fre uenc t a
min


22,9 834,5 0,10 3% 54% Diabetes os.
3,05


22,9 869,4 0,17 14% 63% Diabetes os.
3,03


24,2 874,5 0,09 28% 66% Diabetes os.
1,89


22,2 907,5 ~- 0,13 0% 41 % Diabetes os.
2,19


29,0 910,5 0,09 15! 47/~ Diabetes os.
2,35


22,9 947,6 0,22 17% 51 % Diabetes os.
3,18


26,8 950,5 0,12 0% 24% Diabetes os.
2,98


23,2 995,6 0,14 23% 50% Diabetes os.
4,87


27,4 1082,6 0,16 0% 44% Diabetes os.
3,59


32,3 1096,5 0,14 10% 51 % Diabetes os.
1,99


26,8 1176,6 0,13 21 % 59/~ Diabetes os.
3,85


22,3 1222,8 0,22 17% 56% Diabetes os.
3,45


30,6 1236,6 0,11 24% 59% Diabetes os.
3,31


52,6 1285,0 0,09 14% 54% Diabetes pos
4,80 ~
~




CA 02473814 2004-07-13
-59-
28,8 1332,7 0,20 23% 55% Diabetes pos.
3,98


49,8 1332,8 0,16 8% 38% Diabetes os.
4,72


26,7 1355,8 0,15 17% 56% Diabetes os.
2,79


24,6 1386,8 0,14 53% 77% Diabetes os.
2,84


26,8 1403,7 0,21 8% 46'% Diabetes os.
3,26


17,8 1405,9 0,15 14% 56% Diabetes os.
4,12


31,5 1442,7 0,27 15% 55% Diabetes os.
3,71


32,1 1449,8 0,14 41% 85% Diabetes os.
3,38


31,3 1592,4 0,38 3% 46/ Diabetes os.
5,27


43,4 1783,4 0,30 33% _ Diabetes os.
4,41 63%


29,4 1789,2 0,39 28% 75% Diabetes os.
3,08


38,4 1818,9 0,21 28% 67% Diabetes os.
1,09


37,7 1821,4 0,39 14% 56% Diabetes os.
1,04


24,4 1829,2 0,23 45% 81 % Diabetes os.
2,55


51,1 1854,7 0,41 14% 54% Diabetes os.
4,11


37,6 1856,8 0,48 33% 56% Diabetes os.
3,30


24,7 1872,9 0,35 43% 72% Diabetes os.
2,63


28,3 1949,5 0,32 17% 73% Diabetes os.
3,47


31,6 1955,1 0,32 55% 79,r Diabetes os.
2,90


31,3 1971,0 0,45 20% 54% Diabetes os.
3,00


37,8 2032,0 0,30 25% 60% Diabetes os.
2,40


30,9 2061,4 0,58 10% 38.% Diabetes os.
4,69


33,8 2092,2 0,46 18% 45% Diabetes os.
3,76


27,7 2185,6 0,46 10% 36% Diabetes os.
4,43


32,9 2189,4 0,34 14% 54% Diabetes os.
1,48


39,6 2229,4 _+ 0,485% 39% Diabetes os.
5,31


24,5 2229,9 0,33 25% 63% Diabetes os.
5,14


28,3 2502,9 0,56 20% 48% Diabetes os.
3,30


24,9 2621,6 0,97 20% 45% D
4,84 iabetes os.


37,5 2669,8 0,39 23% 67rb _
4,52 _
Diabetes pos.


20,8 2752,2 0,76 35% 64% Diabetes os.
4,47


24,9 27_95,7 0,96 13% 40% Diabetes os.
4,31


48,2 3246,1 0,43 0% 30ro Diabetes os.
3,61


20,9 3844,0 0,52 3% 54% Diabetes os.
3,33


21,9 4961,5 0,89 10% 40% Diabetes os.
2,62


18,6 5497,0 ~ 0,66 18% 42% Diabetes os.
2,91


20,4 808,4 0,10 58% 9% Diabetes ne .
2,20


45,3 897,5 0,09 48% 7/n Diabetes ne .
2,03


31,4 929,5 0,11 98% 46% Diabetes ne .
1,08


41,2 946,4 0,10 85% 36% Diabetes ne .
1,41


28,0 980,5 0,07 85% 31 % Diabetes ne .
1,04


26,7 1000,5 0,09 83% 41 % Diabetes neg.
2,26


27,8 1008,5 0,10 95% 4 Diabetes ne .
1,51 1 %


29,3 1012,5 -~ 0,1063% _ Diabetes ne .
2,55 17%


43,6 1047,5 0,11 90% 26% Diabetes ne .
2,03


25,0 1052,6 0,08 45% 4% Diabetes ne .
3,91


37,4 1066,5 +_ 0,1458% 13% Diabetes ne .
5,63


22,8 1075,5 0,13 68% 26/~ Diabetes ne .
1,78


28,9 1088,6 0,15 65% 21 % Diabetes neg
3,89
~




CA 02473814 2004-07-13
-60-
44,4 1106,5 0,11 80% 18% Diabetes ne .
2,06


34,1 1107,5 0,10 ____88% _ Diabetes ne .
1,80 35%


42,8 1120,5 0,06 60% __ Diabetes ne .
3,26 14'%


29,1 1134,6 0,10 95% 49% Diabetes ne .
2,26


28,2 1137,7 0,11 _ 70% 24~% Diabetes ne .
3,00


45,5 1139,5 0,20 83% 22% Diabetes ne .
2,34


32,9 1159,6 0,11 80% 27% Diabetes ne .
1,25


23,3 1180,5 0,16 50% 9% Diabetes ne .
4,17 _ v


43,8 1200,6 0,11 95% 50! Diabetes ne
2,08 .


27,2 1204,6 0,17 60% 17% Diabetes neg
3,22


44,9 1209,5 0,09 83% 17~/0 Diabetes ne .
2,53


47,8 1224,6 0,12 75% 19% Diabetes ne .
2,73


25,6 1246,7 0,15 73% 30% Diabetes ne .
2,43


47,9 1268,6 0,09 68% 25t Diabetes ne .
2,66


43,9 t 1277,5 0,10__70% 28% Diabetes ne .
1,80


46,0 1278,5 0;09 58% 10% Diabetes ne .
2,69


33,1 1282,6 0,13 62% 7% Diabetes ne .
1,82


29,3 1331,7 0,18 65% 12% Diabetes ne .
3,88


45,9 1405,5 0,33 93% 45% Diabetes ne .
4,78


44,4 -~ 1423,6 0,16 60% 20JO Diabetes ne .
3,90


19,2 1484,8 0,19 68% 13% Diabetes ne .
3,40


36,9 1609,6 0,13 85% 13% Diabetes ne .
2,02


38,9 1639,7 0,27 63% 19% Diabetes ne .
3,78


33,2 1662,9 0,21 62% 5% Diabetes ne .
3,34


35,8 _ 66% 10% Diabetes ne .
2,19 1664,6 0,29


36,2 1666,6 0,34 75% 29io Diabetes ne .
4,78


35,9 1678,1 0,44 60% 18! Diabetes ne .
2,98


37,3 1716,8 0,23 73% 19% Diabetes ne .
2,99


46,5 1717,5 0,37 79% 15~~ Diabetes ne .
4,38


37,9 1746,0 0,33 83% 34% Diabetes ne .
4,18


25,1 1817,6 0,27 65% 8% Diabetes ne .
2,25


34,2 1823,4 0,47 73% 30% Diabetes ne .
3,95


29,1 1849,8 0,30 100% 56/~ Diabetes ne .
3,59


49,3 1914,1 0,36 88% 38% Diabetes ne .
4,49


44,2 1916,7 0,33 69% 10/> Diabetes ne .
4,23


39,8 2030,8 _+ 0,3593% 38% Diabetes ne .
2,19


31,9 2118,9 0,21 73% 14% Diabetes ne .
1,61


41,2 2179,3 0,42 58% 17% Diabetes ne .
2,45


20,1 2219,0 0,26 53% 13% Diabetes ne .
2,78


25,8 2256,9 0,47 85% 26% Diabetes neg.
2,70


45,1 2273,4 0,42 79% 22% Diabetes ne .
5,23


40,7 2279,0 0,33 90% 20% Diabetes ne .
1,90


26,8 2320,2 0,55 78% 34% Diabetes ne .
3,73


23,6 2332,2 0,35 53% 11 % Diabetes ne .
3,10


44,5 2345,6 0,46 75% 34% Diabetes ne .
3,08


25,7 2384,5 0,63 65% 21 % Diabetes ne .
5,16


38,5 2423,9 +_ 0,4188% 29% Diabetes ne .
3,62


34,2 2429,9 0,51 65% 18% Diabetes ne .
2,92


23,3 2443,3 0,46 66% 5% Diabetes ne .
2,54




CA 02473814 2004-07-13
-61-
41,7 3,722548,1 0,57 _ 69% _ Diabetes ne .
15%


27,3 4,772548,3 0,66 83% __ Diabetes ne .
_
35%


43,6 2,082548,3 0,23 95% _ Diabetes ne .
41 %


24,0 3,112581,5 0,47 60% 13% Diabetes ne .


24,0 2,702587,4 0,40 80% 26% Diabetes ne .


41,7 3,062606,8 0,55 78% 35% Diabetes ne .


31,3 4,922636,4 0,48 72% 12% Diabetes ne .


25,5 -~ 2644,2 0,41 88% 33% Diabetes ne .
3,62


29,2 1,072654,0 0,37 66% 0% Diabetes ne .


29,8 3,502698,2 0,63 90% 29% Diabetes ne .


43,0 2,262710,5 0,37 79% 5~% Diabetes ne .


25,1 1,642761,3 0,35 88% 44% Diabetes ne .


31,3 2,792808,5 0,56 79% 22% Diabetes ne .


42,0 3,222876,5 0,48 62% 7% Diabetes ne .


33,7 3,342898,7 0,50 85% 43~o Diabetes ne .


42,2 2,682908,1 0,53 72% 17% Diabetes ne .


35,4 2,632917,6 0,58 72% 12% Diabetes ne .


35,4 0,772978,1 0,49 85% 35to Diabetes ne .


36,1 1,422994,6 0,80 83% 24% Diabetes ne .


43,5 2,993023,4 0,65 93% 34% Diabetes ne .


44,4 3,353045,2 0,61 69% 12% Diabetes ne .


22,9 3,473076,4 t 0,96 66% 7% Diabetes ne .


35,7 1,993082,3 0,43 73% 22% Diabetes ne .


33,6 3,533136,8 0,61 95% 47o Diabetes ne .


21,7 3,143154,8 0,44 55% 10~o Diabetes ne .


26,5 1,923193,7 0,53 78% 32% Diabetes ne .


24,4 3,023206,3 0,72 66% 7% Diabetes ne .


28,2 2,803250,9 0,71 63% 18% Diabetes ne .


48,2 3,463293,2 0,74 93% 39% Diabetes ne .


31,4 1,603295,7 0,33 95% 40~~ Diabetes ne .


27,2 3,583338,4 0,79 80% 34% Diabetes ne .


37,3 2,113381,6 0,63 78% 26% Diabetes ne .


27,6 2,493452,1 0,49 58% 15/~ Diabetes ne .


37,3 1,503463,0 0,83 72% 15% Diabetes ne .


19,6 2,893583,4 0,75 79% 20% Diabetes ne .


34,0 2,553634,4 0,74 86% 29% Diabetes ne .


37,7 2,613681,8 1,38 55% 14% Diabetes ne .


25,5 2,253686,2 0,60 86% 20% Diabetes ne .


36,0 3,893735,7 0,57 70% 28% Diabetes ne .


30,3 1,583852,3 0,56 83% 41 % Diabetes ne .


29,6 1,464098,4 0,59 93% 20% Diabetes ne .


28,8 1,185428,8 0,67 70% 19% Diabetes ne .


33,1 0,696187,5 1,13 83% 10% Diabetes ne .


26,0 4,826212,0 1,41 75% 26% Diabetes ne .


23,3 2,199868,8 1;33 66% 0% Diabetes ne .


21,7 5,12830,5 0,11 4% 40% Ne hro ath os.


32,4 1,83866,4 0,11 0% 40% Ne hro ath os.


30,6 3,07909,5 0,13 11 % 40% Ne hro ath os.


32,8 3,14937,5 0,11 14% 73% Ne hro ath os.




CA 02473814 2004-07-13
-62-
24,9 952,5 0,16 _ 11% 40% Ne hroathos.
2,97


32,1 1033,5 0,11 _ 5% 40% Ne hroathos.
2,44 ___-


24,4 1060,6 0,16 17% 68% Ne hroathos.
2,87


27,5 1131,6 0,16 20% 68% Ne hroathos.
2,86


33,4 1181,6 0,15 22% 73% Ne hroathos.
3,48


33,0 1203,6 0,14 9% 50% Ne hroathos.
2,52


26,5 1211,6 0,14 14/~ 40% Ne hroathos.
3,68


33,1 1219,6 0,15 18% 40% Ne hroathos.
0,91


32,8 1225,6 0,13 12% 40% Ne hroathos.
3,30


30,7 1297,7 0,20 31 % 82% Ne hro os.
3,18 ath


34,1 1333,7 0,23 9% 40% Ne hroathos.
2,05


44,7 1337,5 0,20 19% 59% Ne hroathos.
4,06


27,9 1398,8 0,36 29% 77% Ne hroathos.
4,19


21,3 1423,7 0,49 6% 50% Ne hroathos.
5,08


28,1 1439,8 0,19 19% 68% Ne hroathos.
4,95


24,5 1466,0 0,27 9% 77% Ne hroathos.
2,42


27,5 1482,0 0,42 33% 40% Ne hroathos.
4,93


29,8 1482,9 0,28 18% 40% Ne hroathos.
4,43


24,3 1483,7 0,28 26% 91 % Ne hroathos.
2,65


24,6 1500,0 0,20 38% 86l Ne hroathos.
1,98


24,6 1553,1 0,28 14% 64% Ne hroathos.
2,90


29,0 1556,7 0,45 26% 73% Ne hroathos.
4,83


24,2 1567,0 0,22 26% 86t Ne athos.
2,48 hro


28,8 1596,9 0,31 21 % 86% Ne hroathos.
4,53


24,5 1652,8 0,25 14% 59% Ne hroathos.
2,43


26,3 1669,8 0,37 20% 64.% Ne hroathos.
2,63


33,1 1729,2 0,36 6% 45! Ne hroathos.
3,22


30,5 1744,4 0,46 16% 59% Ne hroathos.
4,11


25,1 1754,4 0,41 53% 95% Nee~hropathypos.
3,42


24,2 1776,0 0,27 9% _ Nephropathy ~os.
1,56 . 50/


18,5 1791,0 0,38 7% _ Ne hroathos.
3,55 40/


32,2 1792,9 t 0,31 28% 40% Ne hroathos.
5,38


9,7 2,541799,8 0,29 0% 40% Ne hroathos.


25,3 1810,9 0,38 43% 91 % Ne hroathos.
2,89


24,6 1851,1 0,21 43% 95% Ne hro os.
2,34 ath


27,2 1867,3 0,42 38% 91 % Ne hroathos.
4,46


25,0 1966,0 0,53 16% 40/' Ne hroathos.
3,97


28,7 1982,8 0,57 11 % 40% Ne hroathos.
3,08


29,5 1986,3 0,36 15% 64/n Ne hroathos.
5,53


23,3 2045,9 0,32 32% 40% Ne hro os..
4,46 ath


33,7 2115,1 0,53 30% 40% Ne hroathos.
3,16


20,5 2177,1 0,37 9% 40% Ne hroathos.
2,78


18,1 2241,6 0,41 9% 59% Ne hroathos.
4,24


21,2 2250,7 0,38 23% 64/> Nephropath os.
2,49


27,5 2258,7 0,49 9% 59% Nephroathos.
2,53


20,0 2356,4 0,41 13% 59% _ hroathos.
3,30 Ne


28,1 2391,4 0,42 13% 64% Ne hroathos.
3,95


25,7 2406,1 0,57 20% 77% Ne hroathos.
4,85


X22,8 2423,2 0,53 14% _ Ne os.
4,28 ~ ~64% hro
~ ath




CA 02473814 2004-07-13
-63-
21,9 2427,3 0,40 31 % 91 % Ne hroathos.
4,45


19,2 2465,1. 0,62 9% 77% Ne hroateos.
4,24 _-


25,4 2493,0 0,38 9% 50% Ne hroathos.
5,25


19,5 2494,0 0,66 12% 77'% Ne hro os.
4,66 ath


23,7 2494,9 0,49 7% 40% Ne hro os.
4,27 ath


24,4 2522,0 0,67 17% 82'% Ne hroathos.
5,51


20,1 2540,5 0,54 14% 68% Ne hroathos.
3,61


22,3 2593,5 0,30 7% 55% Ne hroathos.
4,72


20,0 2613,9 0,83 14% 55% Ne athos.
4,87 hro


35,1 2726,5 0,67 61 % 20% Ne hroathos.
1,62


25,0 2775,1 0,56 12% 40% Ne hroathos.
4,39


21,8 2790,7 0,55 19% 86% Ne hroathos.
3,78


25,9 2892,2 0,50 9% 50% Ne hroathos.
3,30


16,8 2919,0 0,26 2% 50% Ne athos.
2,72 hro


21,9 2937,0 0,49 13% 86% Ne hroathos.
3,23


20,0 2958,8 0,80 5% 59% Ne hroathos.
4,81


34,4 2962,0 0,54 12% 20mi Ne hroathos.
2,72


28,9 3059,7 0,78 30% 40% Ne hroathos.
3,56


28,3 3088,0 0,79 7% 20% Ne hroathos.
5,96


26,1 3369,2 0,73 21 % 40% Ne hroathos.
2,72


26,0 3483,4 0,95 30% 40% Ne hroathos.
2,89


24,5 4183,3 1,44 4% 40% Ne hroathos.
3,92


21,0 4241,0 0,62 29% 73% Ne hroathos.
5,35


23,4 4370,2 1,01 11 % 40~ Ne hroathos.
4,09


22,8 4527,6 0,67 1 % 45' Ne hroathos.
2,94


21,7 4713,6 0,44 7% 64% Ne hroathos.
3,00


24,6 7556,6 1,55 2% 40% Ne hroathos.
3,73


16,7 8055,1 2,10 12% 40% Ne hroathos.
5,54


13,2 8765,8 0,96 37% 82% Ne hroathos.
5,19


15,3 9181,0 1,28 10% 64% Ne hroathos.
4,97


14,0 10046,1 0,96 21% 77! Ne hroathos.
4,20


18,7 10208,0 1,24 2% 40% Ne hroathos.
5,50


17,4 f 10518,2 1,10 23% 64% Ne hroathos.
4,02


35,3 924,5 0,12 50% 0% Ne hroathne .
5,04


43,1 928,4 0,08 65% 14% Ne hroathne .
2,61


45,7 955,5 0,14 60% 5% Ne hroathne .
2,25


23,8 1010,6 0,09 67% 5% Ne hroathne .
2,94


31,2 1028,5 0,09 84% 32% Ne hroathne .
1,53


45,9 1041,4 0,10 57% 0/n Ne hroathne .
2,27


31,5 1046,5 0,09 87% 32/n Ne hroathne .
1,98


43,4 1047,5 0,12 68% 0/> Ne hroathne .
2,24


18,1 1050,7 0,12 60% 0% Ne hroathne .
4,34


32,9 1084,4 0,11 69% 18/<> Ne hroathne .
3,03


46,7 1125,5 0,12 63% 9% Ne hroathne .
2,63


46,3 1157,5 0,10 83% 32% Ne hroathne .
2,70


43,7 1160,5 0,07 72% 18% Ne hroathne .
1,70


44,5 1179,5 0,09 97% 36% Ne hroathne .
3,67


45,0 1191,6 0,09 60% 9% Ne hroathne .
2,24


46,2 1195,5 0,10 98% 32% Ne hro ne .
2,59 ath




CA 02473814 2004-07-13
-64-
44,2 1200,6 0,13 -_ 86% 0% Ne hroathne .
1,83


45,9 1223,5 0,10_,-80% 9% Ne hroathne .
2,04


44,5 1239,6 0,08 89% 0% Ne hroathne .
2,15


47,8 1246,6 0,11 60% 5% Ne hroathne .
3,08


46,8 1254,7 0,19 56% 5% Ne hroathne .
2,20


43,2 1261,5 0,16 91 % 36/~ Ne athne .
2,90 hro


48,6 1262,5 0,09 65% 0% Ne hroathne .
2,90


43,9 1277,6 0,11 67% 0% Ne hroathne .
2,16


36,7 1288,7 0,18 72% 23% Ne hroathne .
3,04


47,2 1292,5 0,14 67% 18% Ne hroathne .
3,17


47,8 1308,5 0,09 66% 0% Ne hroathne .
2,58


48,2 1321,6 0,11 53% 0% Ne hro ne .
2,67 ath


34,8 1321,7 0,23 98% 41 % Ne hroathne .
1,81


46,0 1351,7 0,15 63% 9% Ne hroathne .
4,93


47,7 1367,6 0,14 97% 23% Ne athne .
2,99 hro


37,8 1378,6 0,16 87% 36% Ne phro~athrune
2,93 .


47,5 1389,7 0,15 86% 18% Ne hropathy neg.
2,59


46,5 1407,8 0,20 79% 9% Ne hroathathne .
2,28


44,6 1422,1 0,33 70% 0% Ne hroathne .
4,84


45,4 1423,8 0,19 75% 0% Ne hroathne .
3,62


48,0 1424,7 0,16 95% 18% Ne hroathne .
2,97


47,6 1446,7 0,16 92% 23% Ne hroathrie .
3,40


46,5 1450,4 0,25 62% 9% Ne hroathne .
2,95


48,0 1462,6 0,17 97% 9% Ne hroathne .
2,95


35,7 1487,7 0,15 70% 18% Ne hroathne .
1,90


47,8 1490,6 0,12 72% 9l Ne hroathne .
2,35


49,2 1491,7 _+ 0,1281 % 14! Ne hroathne .
2,77


49,0 1507,8 0,17 99% 32% Ne hroafhne .
3,14


49,2 1523,7 0,11 97% 18% Ne hroathne .
2,86


48,6 +_ 1529,7 p,1 83% 9% Ne hroathne .
2,70 g


49,2 1539,7 0,19 98% 23% Ne hroathne .
3,26


49,0 1545,7 0,13 99% 23ro Ne~hro~a~neck.
3,19


49,8 1561,6 0,19 90% 18% Ne hro~athyneg.
2,76


48,4 1567,7 0,20 65% 9io Ne hroathne .
3,12


48,1 1573,7 0,27 63% 5im Ne hroathne .
2,66


48,5 1577,8 0,35 94% 9/~ Ne hroathne .
4,03


50,6 1587,1 0,34 65% 0% Ne hroathne .
3,40


48,6 1589,7 0,14 86% 18 Ne athne .
2,68 l hro


45,9 1591,7 0,30 79% _ Ne hroathne .
3,83 18%


49,3 1594,8 0,14 88% 14/u Ne hroathne .
3,22


48,8 1605,7 0,13 73% 18% Ne hroathne .
2,78


48,5 1611,7 0,14 73% 5% Ne hroathne .
2,81


46,3 1636,4 0,39 79% 23% Ne hroathne .
5,12


49,5 1651,8 0,19 99% 23% Ne hroathne .
3,37


45,2 1657,7 0,23 60% 5% Ne hroathne .
5,96


49,5 1673,8 0,14 95% 23% Ne hroathne .
3,33


49,6 1689,8 0,18 86% 0% Ne hroathne .
3,05


26,9 1706,8 0,30 78% 27% Ne hro ne .
3,18 ath


49,4 1734,4 0,40 65% ( 5% Ne ne .
2,84 ~ hro
' ath




CA 02473814 2004-07-13
-65-
49,2 3,171739,7 0,22 59% 5% Ne ne .
_ hro
ath


45,1 +_ 1748,0 0,28 55% 5% Ne ne .
4,21 hro
ath


44,2 4,711813,6 0,38 58% _ Ne ne .
5% hro
ath


39;1 3,481817,0 0,29 85% 18% Ne hro ne .
ath


51,7 3,481841,0 0,23 59% 9% Ne hro ne .
ath


50,4 4,561848,2 0,43 58% 0% Ne hroathne .


51,5 2,941856,8 0,24 59% 5% Ne hroathne .


52,7 4,241863,8 0,31 88% 14% Ne hroathne .


52,7 3,921885,8 0,20 70% 5% Ne hroathne .


47,7 4,691902,1 0,33 75% 0% Ne hroathne .


50,6 3,951924,0 0,48 68% 0% Ne hroathne .


26,6 1,762048,5 0,44 86% 20% Ne hroathne .


25,8 1,392085,9 0,24 83% 32% Ne hroathne .


39,9 1,452087;8 0,34 72% 23% Ne hroathne .


52,8 4,092117,1 0,17 78% 9% Ne hroathne .


28,3 3,902129,7 0,42 63% 0% Ne hroathne .


40,4 1,532158,9 0,26 86% 32% Ne hroathne .


39,7 1,712174,9 0,36 97% 45% Ne hroathne .


32,6 1,792227,1 0,41 81% 23% Ne hroathne .


29,3 3,502249,0 0,41 92% 41 % Ne hroathne .


40,6 1,252257,1 0,35 94% 45~ Ne hroathne .


46,2 5,112273,5 0,38 71 % 18% Ne hroathne .


40,8 2,662296,0 0,40 63% 20% Ne hroathne .


40,9 3,322327,6 0,52 85% 36% Ne hroathne .


41,8 2,452343,3 0,43 77% 27% Ne hroathne .


40,8 1,312385,3 0,32 95% 45% Ne hroathne .


40,9 2,682471,5 0,52 69% 14% Ne hroathne .


41,5 2,642493,5 0,48 74% 18% Ne hroathne .


52,9 3,982570,4 0,27 71 % 5! Ne hroathne .


34,1 0,722642,8 0,40 86% 36% Ne hroathne .


36,1 2,562687,1 0,49 84% 23% Ne hroathne .


42,8 2,332710,6 0,46 88% 18% Ne hroathne .


50,6 4,732748,6 t 0,36 64% 0% Ne hroathne .


37,8 1,922986,6 0,55. 74% 23/p Ne hroathne .


23,3 2,073007,4 0,50 65% 9% Ne hroathne .


25,9 2,353038,3 0,70 46% 0/~ Ne hroathne .


46,0 2,913045,4 0,36 59% 5/> Ne hroathne .


53,3 4,053057,2 0,64 76% 9% Ne hroathne .


38,9 2,573109,0 0,57 88% 14% Ne hroathne .


41,9 3,553187,6 0,47 71 % 14% Ne hroathne .


26,6 1,153193,6 0,41 61 % 0% Ne h athneck.
ro


48,3 3,693223,8 0,41 88% 18% Ne _ athynet.
h~op


31,7 3,653265,1 0,64 93% 41 % Ne hroathne .


29,5 1,763291,0 0,52 81 % 23% Ne hroathne .


49,2 3,703293,1 0,43 91 % 14% Ne hroathne .


49,9 3,573315,0 0,45 67% 5% Ne hroathne .


43,3 2,043319,9 +_ 0,6686% 23% Ne hroathne .


49,1 3,353336,7 0,38 63% 9% Ne hroathne
.


38,5 2,053359,9 0,42 _ _
~ 98% 41 % Nephropathyneg




CA 02473814 2004-07-13
-66-
38,5 3360,1 0,65 - 98% 20'% Nehroathne .
1,92


38,5 3417,1 0,48 .,_ 95% _ Nehro athne .
2,03 _,_i _.-
45%


38,5 3433,3 0,43 92% - Nehroathne .
1,09 41 %


51,6 3478,9 0,48 74% 5% Nehroathne .
3,50


31,7 3589,7 0,48 73% 18% Nehro ne .
2,29 ath '


33,2 3633,4 0,95 80% 18% Nehroathne .
3,71


36,0 3636,6 0,73 58% 0% Ne athne .
3,18 hro


37,9 3719,5 0,61 67% 9% Ne~hroathne .
2,69


42,0 3739,7 0,99 73% 14% Nehroathne .
3,21


25,8 3947,3 0,67 92% 32% Nehroathne .
1,20


39,4 4006,6 0,49 62% 5% Nehroathne .
1,13


26,0 4044,9 0,56 78% 14% Nehroathne .
3,97


30,5 4070,4 0,48 57% 5% Nehroathne .
2,17


29,5 4098,6 0,52 86% 32% Nehroathne .
0,93


34,3 4102,5 0,50 77% 14t Nehroathne .
2,08


34,7 4290,7 0,52 76% 18t Ne athne .
0,63 hro


23,5 4405,8 0,54 51 % 0% Nehroathne .
1,61


30,4 4801,5 1,06 65% 0! Nehroathne .
1,31


32,4 4863,8 0,64 67% 5% Nehroathne .
1,31


29,5 5214,0 1,29 51 % 0% Nehroathne .
2,25


33,0 6172,0 1,57 65% 0% Nehroathne .
0,99


33,2 6187,8 0,75 95% 45J Nehroathne .
0,75


23,8 9869,7 1,06 69% 14% Nehroathne .
1,86


Table 23:
mi ration time dt min mass Da
min


15,490396 ___0,1588048054,473633


15,803237 0,155143 8765,233398


16,034266 0,174906 1621,9104


16,185061 0,147871 9180,99707


16,645294 0,198704 10045,20703


17,663696 0,165531 10388,81348


17,980883 0,178564 10518,18457


19,917442 0,234131 9220,939453


20,34516 0,170572 1877,789429


20,479975 0,221246 3842,693604


20,519386 0,265078 4747,932617


21,465685 0,217493 4154,003906


21,480436 0,362197 2427,251709


21,804012 0,271715 4240,856445


22,221563 0,191069 4282,796387


22,777784 0,245503 3840;540527


24,304148 0,319715 7556,177734


24,579231 0,291986 879,519653


24Y813087 0,224198 1867,731689


25,283239 0,22054 2266,040771


26,177101 0,289898 2172,188721


26,773794 0,352887 2914,05542




CA 02473814 2004-07-13
-67-
26,81407 0,297343 962,591919


28,254925 0,581783 4353,585938


28,825331 0,258778 1250,62439


29,308136 0,852391 1060,239014


29,822325 0,595913 1682,720947


30,75272 0,175961 943,492859


30,762201 0,263861 1108,647949


30,926645 0,138075 1368,781738


31,305229 0,301605 3987,548828


31,433071 0,515308 1099,419434


32,165497 0,198377 3122,730713


32,222111 0,226858 1829,089966


33,427856 0,151562 2767,015625


34,053886 0,252424 1302,691772


34,15913 0,233032 3722,875977


34,557327 0,186137 2039,143433


34,681156 0,20976 3685,918213


35,30254 0,207782 2389,097168


35,502213 0,388916 3209,800293


36,314056 0,183495 980,526123


36,404907 0,145751 1008,513733


36,424831 0,150486 1000,48761


36,720509 0,128397 2717,472656


36,777012 0,164648 2663,246826


37,557594 0,165628 3556,580566


37,572525 0,185484 1743,890381


37;680653 0,160958 1134,580566


37,700241 0,171622 4097,981934


38,050472 0,156383 3152,361572


38,155159 0,217341 2825,309082


38,17057 0,432096 882,532654


38,281631 0,20781 996,190369


38,57658 0,370648 1425,324829


38,687305 0,15052 3385,513916


38,830559 0,056085 1352,824097


38,921108 0,150325 5000,982422


39,241917 0,178206 3775,720459


39,433277 0,235333 3405,60791


39,484215 0,140887 1046,52771


39,513248 0,093703 2154,053955


39,936756 0,195951 6171,129395


40,533363 0,158628 1194,581543


40,537457 0,221485 2205,064941


40,607231 0,426674 1235,384888


40,686531 0,122381 1265,634888


40,83009 0,191972 2642,264893


41,506096 0,161887 4159,304199


41,604115 0,217324 1250,585449


41,818069 0,163642 2742,253418


42,079609 0,266392 1463,643311


42,105633 0,172054 1489,658936


42,131275 0,184863 1473,643555




CA 02473814 2004-07-13
-6~-
42,144161 __ Oi162_7161451, 710938


42,573879 0,234118 _,-_
3
098,450928


42,636433 0,041732 _
1487,660034


42,811199 0,246696 1579,670776


42,940624 0,1884 3121,243164


43,093792 0,106392 3271,523438


43,115334 0,607341 1834,878052


43,46143 0,193155 3442,135498


43,494144 0,20218 3495,841797


43,549488 0,217899 3473,905029


43,740391 0,12795 3108,919434


44,191006 0,18629 3359,583496


44,230297 0,233319 3416,526611


44,934914 0,127421 1991,917114


45,538418 0,214716 2197,337158


45,675098 0,12333 1889,864502


46,313114 0,259721 2385,597168


47,216648 0,168651 2649,602539


47,279705 0,127824 2343,072998


47,526871 0,19233 2584,635986


48,441795 0,239347 1160,526001


48,804813 0,251244 1261,53125


49,519478 0,243133 1274,625244


51,416531 0, 33207 1195, 518677


51,492035 0,213235 1211,559204


51,657627 0,822884 1223,348633


53,168346 0,293424 1351,643433


53,240913 0,216809 1367,655151


53,259499 0,15916 1770,30481


54,59832 0,234281 1507,742432


55,038143 0,329349 1594,211426


57,475471 0,325805 1840,810547


58,191887 0,1' 29 2021,900879


58,898354 0,484288 2608,239746


60,082333 ( 0 507699 1863,939453
~


Table 24:
mi ration tirnedt min mass Da
min


12,295616 0,0_92835 8053,516


12,33161 9 0,12201 1621,946


12,508785 0,139706 8765,729


12,696615 0,122507 9181,114


12,906662 0,115952 10046,58


13,103853 0,041984 2427,001


14,332394 0,144029 4153,814


14,426023 0,131007 4240,702


14,496774 0,385605 3841,615


14,585806 0,105399 4282,281


15,094264 0,132582 879,5324




CA 02473814 2004-07-13
-69-
15,123884 0,069059 1868,033


15,236325 0,136994 7555,679


15,641728 0,159929 962,6218


16,194395 0,167525 1060,664


16,280394 0,28676 4353,476


16,363562 0,082856 1682,889


16,427116 0,09725 1743,982


16,50071 0,133981 1108,646


16,904119 0,128321 1829,115


17,017418 0,23895 3987,366


17,409172 0,158398 2767,263


17,716999 0,1571 1302,722


17,891594 0,202698 3722,962


18,049681 0,191037 2039,257


18,140236 0,176836 3686,508


18,528196 0,076336 3209,884


19,106394 0,148381 1008, 572


19,118612 0,156251 1000,564


19,173443 0,122128 980,5635


19,335644 0,098819 2663,262


19,367334 0,112794 2718,314


20,023649 0,199337 3556,408


20,041323 0,195353 1134,629


20,063593 0,224531 4098,26


20,300522 0,113124 3152,333


20,347666 0,200969 882,5596


20,470793 0,208903 2825,334


20,889994 0,26629 3385,819


20,93943 0,057322 1425,772


21,519066 0,226397 5000,98


21,655712 0,298068 3775,697


21,755213 0,316991 1046,586


21,850452 0,518151 3405,871


22,747589 0,302407 1235,601


22,763943 0,277557 1194,603


22,997269 0,34528 1265,661


23,013165 0,225846 2642,188


23,017294 0,551478 6171,03


23,838888 0,406385 12'50,653


24,025209 0,261109 2742,267


24,137253 0,135523 1463,693


24,14039 0,158709 1473,664


24,220345 0,206216 1489,686


24,355286 0,409203 1451,684


24,686199 0,240303 3098,376


24,915867 0,332783 1579,718


25,093962 0,214003 3121,259


25,181305 0,33936 3272,276


25,634459 0,407648 3441,958




CA 02473814 2004-07-13
-70-
25,648405 0,344555 3495,801


25,928818 0,283113 3108,66


26,411203 0,355909 3359,75


26,493782 0,341234 3416,324


27,775286 0,346393 2196,686


28,415859 0,219954 2385,565


29,471397 0,2699 2649,791


29,74654 0,131224 2584,214


30,499264 0,32736 1160,556


30,832899 0,269278 1261,477


32,240211 0,415696 1195,543


32,240601 0,406316 1223,53


32,29216 0,268596 1212,024


33,24297 0,403599 1367,633


34,039223 0,467469 1507,75


34,274136 0,432896 1594,746


35,978645 0,326975 1841,202


37,237282 0,110906 2608,186


37,342949 0,6411 1863,833


Table 25:
Sex Age DiagnosisS-creatinineProteinuriaIrn
munosuppression
~


M 63 FSGS 95 0.02 _
pS


M 18 FSGS 99 0.05 _
_
CsA


M 63 FSGS 93 0.05 pS


F 49 FSGS 80 0.05 CsA+pS


F 23 FSGS 69 0.54 CsA


F 26 FSGS 16 0,7 CsA


F 56 FSGS 80 0.8


M 62 FSGS 150 1,9


M 26 FSGS 144 4,9 _


F 26 FSGS 150 11.0 CsA+PS


M 69 MGN 128' 0.02 CsA


M 62 MGN 91 0.17


M 23 MGN 150 0.3


M 37 MGN 73 0.33


M 43 MGN 82 0.7 PS


M 48 MGN 100 1.0 CsA+PS


F 68 MGN 150 1.0


F 21 MGN 80 1.0 CsA+PS


M 44 MGN 118 1.0 CsA


M 45 MGN 93 1.3


M 48 MGN 133 2.4 _


M 37 MGN 93 2.6


M 78 MGN 99 3.3 _


M 47 MGN 93 3.5 pS


F 34 MGN 80 3.5 CsA+PS


M 66 MGN 132 3,6 ..




CA 02473814 2004-07-13
_'
M 38 MGN _100 4.0 CsA+PS


M 43 MGN _ 85 5.1 -


F 43 MCD 114 0.01 CsA


M 45 MCD + 93 0.01


F 52 MCD + 118 0.01 -


M 52 MCD 93 0.01 -


F 44 MCD + 80 0.02 CsA


M 39 MCD * 93 0.02 -


M 51 MCD 93 0.05 -


M 18 MCD 77 0.05 CsA+PS


F 70 MCD * 95 0.08


M 69 MCD 93 0.08 -


F 29 MCD + 160 0.1


M 62 MCD + 93 0.1 -


M 21 MCD 57 0.12 _
-


F 43 MCD 114 0,01 CSA


F 25 MCD 80 1,2


M 52 MCD 93 0.4 ~ pS


F 80 MCD * 145 __
7.9

Representative Drawing