# US 10,246,518 B2 · Nucleic acids encoding bispecific antibodies binding to beta-Klotho and fibroblast growth factor receptor 1

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

- Number: US 10,246,518 B2
- Document ID: US10246518B2
- Status: Granted
- Kind: B2
- Application number: 15/837,801
- Filed: 2017-12-11
- Published: 2018-04-19
- Granted: 2019-04-02
- Earliest claimed: 2013-12-23
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Yongmei Chen; James Ernst; Hok Seon Kim; Junichiro Sonoda; Christoph Spiess; Scott Stawicki; Yan Wu
- Web page: https://patentgrep.com/patent/US10246518B2

## CPC

- C07K 16/40: against enzymes
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/12: Antihypertensives
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- 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 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/71: for growth factors; for growth regulators
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- 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 2317/40: characterized by post-translational modification
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/524: CH2 domain
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/75: Agonist effect on antigen
- 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
- 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)

## Abstract

The presently disclosed subject matter provides antibodies that bind KLB and FGFR1, and methods of using the same. In certain embodiments, an antibody of the present disclosure includes a bispecific antibody that binds to an epitope present on FGFR1 and binds to an epitope present on KLB.

## Claims

### Claim 1

A nucleic acid encoding a bispecific antibody, or an antigen-binding portion thereof, that binds to beta-Klotho (KLB) and Fibroblast Growth Factor Receptor 1c (FGFR1c), wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
(i) a first arm comprising (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 136; (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 137; (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 138; (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 139; (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 140; and (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 141; and
(ii) a second arm comprising (a) a heavy chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 15; (b) a heavy chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 31; (c) a heavy chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 47; (d) a light chain variable region CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 62; (e) a light chain variable region CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 78; and (f) a light chain variable region CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 93.

### Claim 2 (depends on 1)

The nucleic acid of claim 1, wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
(a) a first arm comprising: a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 132 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 134; and
(b) a second arm comprising: a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises amino acids having the sequence set forth in SEQ ID NO: 128, and the light chain variable region comprises amino acids having the sequence set forth in SEQ ID NO: 130.

### Claim 3 (depends on 2)

The nucleic acid of claim 2, wherein the first arm comprises a heavy chain and a light chain, wherein the heavy chain comprises amino acids having the sequence set forth in SEQ ID NO: 133, and the light chain comprises amino acids having the sequence set forth in SEQ ID NO: 135.

### Claim 4 (depends on 2)

The nucleic acid of claim 2, wherein the second arm comprises a heavy chain and a light chain, wherein the heavy chain comprises amino acids having the sequence set forth in SEQ ID NO: 129, and the light chain comprises amino acids having the sequence set forth in SEQ ID NO: 131.

### Claim 5 (depends on 2)

The nucleic acid of claim 2, wherein the bispecific antibody, or an antigen-binding portion thereof, comprises:
(a) a first arm comprising a heavy chain region and a light chain region, wherein the heavy chain region comprises amino acids having the sequence set forth in SEQ ID NO: 133, and the light chain region comprises amino acids having the sequence set forth in SEQ ID NO: 135; and
(b) a second arm comprising a heavy chain region and a light chain region, wherein the heavy chain region comprises amino acids having the sequence set forth in SEQ ID NO: 129, and the light chain region comprises amino acids having the sequence set forth in SEQ ID NO: 131.