# US 9,751,943 B2 · Compositions and methods including a recombinant human MAB that promotes CNS remyelination

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- Number: US 9,751,943 B2
- Document ID: US9751943B2
- Status: Granted
- Kind: B2
- Application number: 14/603,553
- Filed: 2015-01-23
- Published: 2015-10-22
- Granted: 2017-09-05
- Earliest claimed: 2003-05-16
- Assignees: Acorda Therapeutics, Inc.; Mayo Foundation for Medical Education and Research
- Applicants: Mayo Foundation for Medical Education & Research; Acorda Therapeutics, Inc.
- Inventors: Elliott A. Gruskin; Arthur E. Warrington; Allan J. Bieber; Moses Rodriguez; Eric Walter Theodore Chojnicki
- Web page: https://patentgrep.com/patent/US9751943B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 39/39533: {against materials from animals}
- A61K 39/39541: {against normal tissues, cells}
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 31/12: Antivirals
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/18: against material from animals or humans
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/75: Agonist effect on antigen
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Antibodies, and particularly human antibodies, are disclosed that demonstrate activity in the treatment of demyelinating diseases as well as other diseases of the central nervous system that are of viral, bacterial or idiopathic origin, including neural dysfunction caused by spinal cord injury. Neuromodulatory agents are set forth that include and comprise a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, a hapten, active fragments thereof, agonists thereof, mimics thereof, monomers thereof and combinations thereof. Methods are described for treating demyelinating diseases, and diseases of the central nervous system of humans and domestic animals, using polyclonal IgM antibodies and human monoclonal antibodies sHIgm22(LYM 22), sHIgm46(LYM46) ebvHIgM MSI19D10, CB2bG8, AKJR4, CB2iE12, CB2iE7, MSI19E5 and MSI10E10, active fragments thereof and the like. The invention also extends to the use of human antibodies, fragments, peptide derivatives and like materials, and their use in above referenced therapeutic applications, and to pharmaceutical compositions containing them, that may be administered in desirably low doses to treat conditions involving demyelination and to promote remyelination.

## Claims

### Claim 1

A therapeutically effective pharmaceutical composition comprising:
an antibody capable of stimulating remyelination comprising the heavy chain variable regions CDR1, CDR2 and CDR3 sequences as set out in FIG. 5 and SEQ ID NO:7 and the light chain variable region CDR1, CDR2 and CDR3 sequences as set out in FIG. 6 and SEQ ID NO:9; the antibody selected from the group consisting of: a human monoclonal antibody mAb sHIgM22 (LYM 22), active fragments thereof, or recombinant antibodies derived therefrom;
a therapeutic compound, drug, or agent useful in neuroregenerative therapy or remyelination; and
a pharmaceutically acceptable carrier, vehicle or diluent,
wherein said composition comprises antibody in a dose range of 1.25 μg antibody/kg body weight to 2.5 μg antibody/kg body weight.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein said composition comprises a dose selected from 1.25 μg antibody/kg body weight, 1.3 μg/kg, 1.4 μg/kg, 1.5 μg/kg, 1.6 μg/kg, 1.7 μg/kg, 1.8 μg/kg, 1.9 μg/kg, 2.0 μg/kg, 2.1 μg/kg, 2.2 μg/kg, 2.3 μg/kg, 2.4 μg/kg, and 2.5 μg antibody/kg body weight.

### Claim 3

A therapeutically effective pharmaceutical composition comprising:
an antibody capable of stimulating remyelination comprising the heavy chain variable regions CDR1, CDR2 and CDR3 sequences as set out in FIG. 5 and SEQ ID NO:7 and the light chain variable region CDR1, CDR2 and CDR3 sequences as set out in FIG. 6 and SEQ ID NO:9; the antibody selected from the group consisting of: a human monoclonal antibody mAb sHIgM22 (LYM 22), active fragments thereof, or recombinant antibodies derived therefrom;
a therapeutic compound, drug, or agent useful in neuroregenerative therapy or remyelination; and
a pharmaceutically acceptable carrier, vehicle or diluent, wherein said antibody comprises a single unit dose of antibody that is 500 ng.

### Claim 4 (depends on 1, 2, 3)

The composition of any of claims 1-3 wherein said antibody comprises a heavy chain variable region amino acid sequence as set out in FIG. 5 and SEQ ID NO: 7 and a light chain variable region amino acid sequence as set out in FIG. 6 and SEQ ID NO: 9.

### Claim 5 (depends on 1, 2, 3)

The composition of any of claims 1-3 wherein the compound, drug or agent is a therapeutic compound for the treatment of multiple sclerosis.

### Claim 6 (depends on 5)

The composition of claim 5 wherein the therapeutic compound is an anti-inflammatory agent, a steroid, a beta interferon formulation or copolymer 1.

### Claim 7 (depends on 1, 2, 3)

A method of reducing or inhibiting demyelination of the central nervous system in a mammal having a demyelinating disease or demyelinating neurological condition which comprises administering to said mammal the composition of any of claims 1-3.

### Claim 8 (depends on 7)

The method of claim 7 wherein the compound, drug or agent in the composition is a therapeutic compound for the treatment of multiple sclerosis.

### Claim 9 (depends on 7)

The method of claim 7 wherein said disease or condition is selected from multiple sclerosis, a viral disease of the central nervous system, and acute or chronic spinal cord injury.

### Claim 10 (depends on 7)

The method of claim 7 wherein said viral disease of the central nervous system is post-infectious encephalomyelitis.

### Claim 11 (depends on 7)

The method of claim 7 wherein the method of administration is selected from intravenous, intraperitoneal, intrathecal, subcutaneous, sublingual, intramuscular, rectal, respiratory and nasopharyngeal administration.

### Claim 12 (depends on 7)

The method of claim 7, wherein the administering step comprises administration in a single dose.

### Claim 13 (depends on 7)

The method of claim 7, wherein the administering step comprises administration in multiple separated or divided doses.

### Claim 14 (depends on 1, 2, 3)

A method of stimulating remyelination of central nervous system axons in a mammal which comprises administering to said mammal the composition of any of claims 1-3.

### Claim 15 (depends on 14)

The method of claim 14 wherein the compound, drug or agent in the composition is a therapeutic compound for the treatment of multiple sclerosis.

### Claim 16 (depends on 14)

The method of claim 14 wherein the method of administration is selected from intravenous, intraperitoneal, intrathecal, subcutaneous, sublingual, intramuscular, rectal, respiratory and nasopharyngeal administration.

### Claim 17 (depends on 14)

The method of claim 14, wherein the administering step comprises administration in a single dose.

### Claim 18 (depends on 14)

The method of claim 14, wherein the administering step comprises administration in multiple separated or divided doses.