# US 11,299,553 B2 · Anti-plasma kallikrein antibodies

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- Number: US 11,299,553 B2
- Document ID: US11299553B2
- Status: Granted
- Kind: B2
- Application number: 16/199,453
- Filed: 2018-11-26
- Published: 2019-06-20
- Granted: 2022-04-12
- 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/US11299553B2

## 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

An isolated antibody that binds human plasma kallikrein (PKal), wherein the antibody comprises a heavy chain variable region that comprises complementarity determining region 1 (HC CDR1) having the sequence HYIMM (SEQ ID NO: 62), a complementarity determining region 2 (HC CDR2) having the sequence GIYSSGGITVYADSVKG (SEQ ID NO: 63), and complementarity determining region 3 (HC CDR3), and wherein the HC CDR3 comprises the sequence:
(i) RRIGIPRRDAFDI (SEQ ID NO: 28),
(ii) RRIGIPRRDEFDI (SEQ ID NO: 29),
(iii) RRTGAPRRDAFDI (SEQ ID NO: 30),
(iv) RRTGSPRRDAFDI (SEQ ID NO: 31),
(v) RRTGLPRRDAFDI (SEQ ID NO: 32), or
(vi) RRTIGPRRDEFDI (SEQ ID NO: 33); and
a light chain (LC) variable region that comprises a complementarity determining region 1 (LC CDR1) having the sequence RASQSISSWLA (SEQ ID NO: 59), a complementarity determining region 2 (LC CDR2) having the sequence KASTLES (SEQ ID NO: 60), and a complementarity determining region 3 (LC CDR3) having the sequence QQYNTYWT (SEQ ID NO: 61).

### Claim 2 (depends on 1)

The isolated antibody of claim 1, wherein the heavy chain variable region comprises F27, F29, or both in the framework region 1 (FR1) with respect to the amino acid sequence of SEQ ID NO: 37.

### Claim 3 (depends on 1)

The isolated antibody 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 4 (depends on 1)

The isolated antibody 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 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

A pharmaceutical composition comprising an antibody of claim 1 and a pharmaceutically acceptable carrier.

### Claim 8 (depends on 1)

A nucleic acid comprising a nucleotide sequence encoding an antibody of claim 1.

### Claim 9 (depends on 8)

A vector comprising the nucleic acid of claim 8.

### Claim 10 (depends on 9)

The vector claim 9, wherein the vector is an expression vector.

### Claim 11 (depends on 10)

A host cell comprising the expression vector of claim 10.

### Claim 12 (depends on 11)

The host cell of claim 11, wherein the host cell is a mammalian cell.

### Claim 13 (depends on 12)

The host cell of claim 12, wherein the mammalian cell is a Chinese Hamster Ovarian (CHO) cell.

### Claim 14 (depends on 13)

A method of producing an antibody, comprising:
culturing the host cell of claim 13 in a culture medium, thereby producing the antibody.

### Claim 15 (depends on 14)

The method of claim 14, comprising recovering the antibody from the culture medium.

### Claim 16 (depends on 15)

The method of claim 15, further comprising purifying the antibody.