# US 12,110,343 B2 · Anti-plasma kallikrein antibodies

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,110,343 B2
- Document ID: US12110343B2
- Status: Granted
- Kind: B2
- Application number: 17/684,460
- Filed: 2022-03-02
- Published: 2023-01-05
- Granted: 2024-10-08
- Earliest claimed: 2013-03-15
- Assignees: Takeda Pharmaceutical Company Limited
- Applicants: Takeda Pharmaceutical Company Limited
- Inventors: Andrew Nixon; Jon A. Kenniston; Stephen R. Comeau
- Web page: https://patentgrep.com/patent/US12110343B2

## CPC

- C07K 16/40: against enzymes
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are antibodies capable of binding to plasma kallikrein and inhibit its activity. Such antibodies interact with one or more critical residues in the catalytic domain of the plasma kallikrein. The antibodies may also contain specific heavy chain complementarity determining region 3 (CDRs) motifs and optionally specific residues at certain positions within both the heavy chain variable region and the light chain variable region.

## Claims

### Claim 1

A method for inhibiting plasma kallikrein (pKal) activity, comprising administering to a subject an effective amount of an antibody that binds pKal, wherein the antibody comprises:
a heavy chain variable region that comprises a complementarity determining region 1 (HC CDR1) comprising the sequence HYIMM (SEQ ID NO: 62), a complementarity determining region 2 (HC CDR2) comprising the sequence GIYSSGGITVYADSVKG (SEQ ID NO: 63), and a complementarity determining region 3 (HC CDR3) comprising the sequence (HC CDR3) comprising the sequence
(i)
(SEQ ID NO: 28)
RRIGIPRRDAFDI;
(ii)
(SEQ ID NO: 29)
RRIGIPRRDEFDI;
(iii)
(SEQ ID NO: 30)
RRTGAPRRDAFDI;
(iv)
(SEQ ID NO: 31)
RRTGSPRRDAFDI;
(v)
(SEQ ID NO: 32)
RRTGLPRRDAFDI;
or
(vi)
(SEQ ID NO: 33)
RRTGIPRRDEFDI;
and
a light chain (LC) variable region that comprises a complementarity determining region 1 (LC CDR1) comprising the sequence RASQSISSWLA (SEQ ID NO: 59), a complementarity determining region 2 (LC CDR2) comprising the sequence KASTLES (SEQ ID NO: 60), and a complementarity determining region 3 (LC CDR3) comprising the sequence QQYNTYWT (SEQ ID NO: 61).

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody is a full-length antibody or an antigen-binding fragment thereof.

### Claim 3 (depends on 2)

The method of claim 2, wherein the antibody is an IgG.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antibody is a human antibody or a humanized antibody.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antibody inhibits the activity of pKal by at least 80%.

### Claim 6 (depends on 1)

The method of claim 1, wherein the antibody has a Ki,app lower than about 1 nM.

### Claim 7 (depends on 1)

The method of claim 1, wherein the light chain variable region further comprises G57 in the framework region 3 (FR3) with respect to the amino acid sequence of SEQ ID NO: 34.

### Claim 8 (depends on 1)

The method of claim 1, wherein the light chain variable region further comprises N45 in the framework region 2 (FR2) with respect to the amino acid sequence of SEQ ID NO: 34.

### Claim 9 (depends on 1)

The method of claim 1, wherein the antibody preferentially binds an active pKal.

### Claim 10 (depends on 1)

The method of claim 1, wherein the subject is a human patient diagnosed with a disease, wherein the disease is rheumatoid arthritis, gout, intestinal bowel disease, oral mucositis, neuropathic pain, inflammatory pain, spinal stenosis, arterial or venous thrombosis, post-operative ileus, aortic aneurysm, osteoarthritis, vasculitis, edema, hereditary angioedema, cerebral edema, pulmonary embolism, stroke, clotting induced by ventricular assistance devices or stents, peri-tumor brain edema, sepsis, acute middle cerebral artery ischemic event, restenosis, systemic lupus erythematosus nephritis, or diabetic macular edema.