# US 2018/0021402 A1 · Modulators of complement activity

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- Number: US 2018/0021402 A1
- Document ID: US20180021402A1
- Status: Published application
- Kind: A1
- Application number: 15/547,085
- Filed: 2016-01-28
- Published: 2018-01-25
- Earliest claimed: 2015-01-28
- Assignees: Ra Pharmaceuticals, Inc.
- Applicants: Ra Pharmaceuticals, Inc.
- Inventors: Michelle Denise Hoarty; Ketki Ashok Dhamnaskar; Daniel Elbaum; Kristopher Josephson; Kelley Cronin Larson; Zhong Ma; Nathan Ezekiel Nims; Alonso Ricardo; Kathleen Seyb; Guo-Qing Tang; Douglas A. Treco; Zhaolin Wang; Ping Ye; Hong Zheng; Sarah Jacqueline Perlmutter
- Web page: https://patentgrep.com/patent/US20180021402A1

## CPC

- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 7/06: Antianaemics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/36: against blood coagulation factors
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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
- 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)

## Abstract

The present invention provides polypeptide modulators of complement activity, including cyclic polypeptide modulators. Also provided are methods of utilizing such modulators as therapeutics.

## Claims

### Claim 1

A method of reducing the cleavage of C5 in a biological system comprising providing a polypeptide to the biological system, wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 184, wherein said polypeptide is provided at a final concentration of from about 0.1 nM to about 50 nM, and wherein cleavage of C5 is reduced by at least 50% relative to cleavage of C5 in the untreated control system.

### Claim 2 (depends on 1)

The method of claim 1, wherein hemolysis is reduced by at least 50% relative to hemolysis in said untreated control system.

### Claim 3

A method of reducing hemolysis in a subject comprising administering a polypeptide at a dose sufficient to achieve plasma levels of said polypeptide of from about 0.2 mg/L (0.1 μM) to about 40 mg/L (20 μM), wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 184, and wherein hemolysis in the subject is reduced by at least 50% relative to hemolysis levels previously observed in said subject.

### Claim 4 (depends on 3)

The method of claim 3, wherein the subject is selected from the group consisting of a human subject, a non-human primate subject, and a porcine subject.

### Claim 5 (depends on 4)

The method of claim 4, wherein said polypeptide is administered to said subject at a dose of from about 0.01 mg/kg to about 20 mg/kg.

### Claim 6 (depends on 5)

The method of claim 5, wherein said administration is carried out daily.

### Claim 7 (depends on 5)

The method of claim 5, wherein said administration is carried out weekly.

### Claim 8

A method of reducing hemolysis in a subject with paroxysmal nocturnal hemoglobinuria (PNH), said method comprising administering a polypeptide to the subject at a dose of from about 0.01 mg/kg to about 20 mg/kg, wherein the peptide comprises an amino acid sequence of SEQ ID NO: 184, and wherein administration is daily, weekly or monthly.

### Claim 9 (depends on 8)

The method of claim 8, wherein said subject has previously been treated with eculizumab.

### Claim 10 (depends on 8)

The method of claim 8, wherein said subject is also receiving treatment with eculizumab.

### Claim 11 (depends on 9, 10)

The method of claim 9 or 10, wherein treatment with eculizumab is ineffective.

### Claim 12 (depends on 11)

The method of claim 11, wherein said polypeptide is administered at a dose of about 0.1 mg/kg to about 10 mg/kg.

### Claim 13 (depends on 12)

The method of claim 12, wherein said polypeptide is administered daily.

### Claim 14 (depends on 12)

The method of claim 12, wherein said polypeptide is administered weekly.

### Claim 15 (depends on 12)

The method of any of claim 12, wherein hemolysis is reduced by at least 50% relative to hemolysis observed previously in said subject.