# US 2014/0194593 A1 · Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use

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- Number: US 2014/0194593 A1
- Document ID: US20140194593A1
- Status: Published application
- Kind: A1
- Application number: 13/756,138
- Filed: 2013-01-31
- Published: 2014-07-10
- Earliest claimed: 1998-09-25
- Assignees: Yeda Research and Development Co. Ltd.
- Inventors: Alexander Gad; Dora Lis
- Web page: https://patentgrep.com/patent/US20140194593A1

## CPC

- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/2026: {IL-4}
- A61K 38/2066: {IL-10}
- A61K 38/215: {IFN-beta}
- A61L 27/22: Polypeptides or derivatives thereof {, e.g. degradation products}
- C07K 5/1019: {with the first amino acid being basic}
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/001: {by chemical synthesis}
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/505: {involving T-cells}
- G01N 33/564: for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9}
- G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)}
- G01N 33/6803: {General methods of protein analysis not limited to specific proteins or families of proteins}
- G01N 33/6812: {Assays for specific amino acids}
- G01N 33/6842: {Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins}
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- G01N 2800/285: Demyelinating diseases; Multipel sclerosis
- Y10T 436/10: Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T 436/105831: Protein or peptide standard or control [e.g., hemoglobin, etc.]
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

The present invention provides processes for determining the molecular weight of glatiramer acetate and other copolymers. The present invention further provides a plurality of molecular weight markers for determining the molecular weight of glatiramer acetate and other copolymers which display linear relationships between molar ellipticity and molecular weight, and between retention time and the log of the molecular weight. The molecular weight markers also optimally demonstrate biological activity similar to glatiramer acetate or corresponding copolymers and can be used for treating or preventing various immune diseases. In addition, the subject invention provides pharmaceutical compositions for the treatment of immune diseases comprising a polypeptide having an identified molecular weight and an amino acid composition corresponding to glatiramer acetate or a terpolymer.

## Claims

### Claim 1

A polypeptide for determining the molecular weight of a copolymer, said polypeptide having an identified molecular weight and an amino acid composition corresponding to said copolymer, wherein the identified molecular weight is between about 2,000 daltons and about 40,000 daltons.

### Claim at position 2

2-3. (canceled)

### Claim 4 (depends on 1)

The polypeptide of claim 1 wherein the copolymer is glatiramer acetate.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The polypeptide of claim 1 wherein said copolymer comprises amino acids alanine, glutamic acid, tyrosine and lysine, and wherein: said alanine is present in a molar fraction of about 0.38 to about 0.50; said glutamic acid is present in a molar fraction of about 0.13 to about 0.15; said tyrosine is present in a molar fraction of about 0.08 to about 0.10; and said lysine is present in a molar fraction of about 0.3 to about 0.4.

### Claim 7 (depends on 1)

The polypeptide of claim 1 wherein said copolymer comprises amino acids alanine, glutamic acid, tyrosine and lysine, and wherein: said alanine is present in a molar fraction of about 0.42 to 0.45; said glutamic acid is present in a molar fraction of about 0.13 to about 0.15; said tyrosine is present in a molar fraction of about 0.08 to about 0.10; and said lysine is present in a molar of about 0.3 to about 0.4.

### Claim at position 7

8-9. (canceled)

### Claim 10 (depends on 6)

The polypeptide of claim 6 which is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7.

### Claim at position 9

11-19. (canceled)

### Claim 20

A plurality of polypeptides for determining the molecular weight of a copolymer on a molecular weight sizing column, which comprises two to about ten polypeptides, each polypeptide having an identified molecular weight and an amino acid composition corresponding to said copolymer and wherein an approximately linear relationship exists between the retention time of said polypeptides on said column and the log of the molecular weight of said polypeptides.

### Claim 21 (depends on 20)

The plurality of polypeptides of claim 20 wherein the identified molecular weight is between about 2,000 daltons and about 40,000 daltons.

### Claim 22 (depends on 20)

The plurality of polypeptides of claim 20 wherein the copolymer is glatiramer acetate.

### Claim 23

(canceled)

### Claim 24 (depends on 20)

The plurality of polypeptides of claim 20 wherein said copolymer comprises amino acids alanine, glutamic acid, tyrosine and lysine, and wherein: said alanine is present in a molar fraction of about 0.38 to about 0.50; glutamic acid is present in a molar fraction of about 0.13 to about 0.15; said tyrosine is present in a molar fraction of about 0.08 to 0.10; and said lysine is a molar fraction of about 0.3 to about 0.4.

### Claim 25 (depends on 20)

The plurality of polypeptides of claim 20 wherein said copolymer comprises amino acids alanine, glutamic acid, tyrosine and lysine, and wherein: said alanine is present in a molar fraction of about 0.42 to about 0.45; said glutamic acid is present in a molar fraction of about 0.13 to about 0.15; said tyrosine is present in a molar fraction of about 0.08 to about 0.10; and said lysine is present in a molar fraction of about 0.3 to about 0.4.

### Claim at position 16

26-29. (canceled)

### Claim 30 (depends on 20)

The plurality of polypeptides of claim 20 which comprises one or more polypeptides selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7.

### Claim at position 18

31-33. (canceled)

### Claim 34 (depends on 20)

A kit comprising the plurality of polypeptides of claim 20.

### Claim at position 20

35-103. (canceled)

### Claim 104

A polypeptide for calibrating a molecular weight discrimination system for measuring the molecular weight of a copolymer said polypeptide having an identified molecular weight and a composition corresponding to said copolymer.

### Claim 105 (depends on 104)

The polypeptide of claim 104 wherein the identified molecular weight is between about 2,000 daltons and about 40,000 daltons.

### Claim 106

(canceled)

### Claim 107 (depends on 104)

The polypeptide of claim 104 wherein the copolymer is glatiramer acetate.

### Claim 108

(canceled)

### Claim 109 (depends on 104)

The polypeptide of claim 104 wherein said copolymer comprises amino acids alanine, glutamic acid, tyrosine and lysine, and wherein: said alanine is present in a molar fraction of about 0.38 to about 0.50; said glutamic acid is present in a molar fraction of about 0.13 to about 0.15; said tyrosine is present in a molar fraction of about 0.08 to about 0.10; and said lysine is present in a molar fraction of about 0.3 to about 0.4.

### Claim 110 (depends on 104)

The polypeptide of claim 104 wherein said copolymer comprises amino acids alanine, glutamic acid, tyrosine and lysine, and wherein: said alanine is present in a molar fraction of about 0.42 to about 0.45; said glutamic acid is present in a molar fraction of about 0.13 to about 0.15; said tyrosine is present in a molar fraction of about 0.08 to about 0.10; and said lysine is present in a molar fraction of about 0.3 to about 0.4.

### Claim at position 28

111-112. (canceled)

### Claim 113 (depends on 109)

The polypeptide of claim 109 which is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7.

### Claim at position 30

114-119. (canceled)

### Claim 120 (depends on 104)

The polypeptide of claim 104 wherein the molecular weight of the copolymer is determined with a molecular size discrimination system and wherein the molecular size discrimination system is a molecular weight sizing column.

### Claim 121

(canceled)

### Claim 122 (depends on 120)

The polypeptide of claim 120 wherein said molecular weight sizing column is selected from the group consisting or a TSK column, a Sephadex column, a Sepharose column, and a Superose column.