# US 8,772,457 B2 · BACE1 antibodies

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

- Number: US 8,772,457 B2
- Document ID: US8772457B2
- Status: Granted
- Kind: B2
- Application number: 13/292,633
- Filed: 2011-11-09
- Published: 2012-06-14
- Granted: 2014-07-08
- Earliest claimed: 2010-11-10
- Assignees: Genentech, Inc.
- Applicants: Jasvinder Atwal; Yongmei Chen; Cecilia Pui Chi Chiu; Robert A. Lazarus; Weiru Wang; Ryan J. Watts; Yan Wu; Yingnan Zhang
- Inventors: Jasvinder Atwal; Yongmei Chen; Cecilia Pui Chi Chiu; Robert A. Lazarus; Weiru Wang; Ryan J. Watts; Yan Wu; Yingnan Zhang
- Web page: https://patentgrep.com/patent/US8772457B2

## CPC

- C07K 16/40: against enzymes
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/6871: {the antibody targeting an enzyme}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/20: Hypnotics; Sedatives
- 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 27/06: Antiglaucoma agents or miotics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12P 21/005: {Glycopeptides, glycoproteins}
- G01N 33/573: for enzymes or isoenzymes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- 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)
- 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
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention provides antibodies to specific neural proteins and methods of using the same.

## Claims

### Claim 1

An isolated antibody, or fragment thereof, that binds to β-site amyloid precursor protein cleaving enzyme 1 (BACE1) comprising
(a) an HVR-H1 comprising the amino acid sequence GFTFX13GYX14IH (SEQ ID NO:26), wherein X13=S or L and X14=A or G,
(b) an HVR-H2 comprising the amino acid sequence of GWISPAGGSTDYADSVKG (SEQ ID NO:24),
(c) an HVR-H3 comprising the amino acid sequence of GPFSPWVMDY (SEQ ID NO:25),
(d) an HVR-L1 comprising the amino acid sequence of RASQX1VX2X3X4X5A (SEQ ID NO:17), wherein X1=D or V; X2=S or A; X3=T or N; X4=S or A; X5=V or L,
(e) an HVR-L2 comprising the amino acid sequence of X6ASFLYS (SEQ ID NO:18) wherein X6=S or L, and
(f) an HVR-L3 comprising the amino acid sequence of QQX7X8X9X10X11X12T (SEQ ID NO:19), wherein X7=S, F, G, D or Y; X8=Y, P, S, or A; X9=T or N; X10=T, Y, D or S; X11=P or L; X12=P or T, and wherein the antibody reduces or inhibits the activity of the BACE1 polypeptide.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the antibody binds to the active site of BACE1.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein the antibody binds to an exosite of BACE1.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein the HVR-H1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO:22 and SEQ ID NO:23.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein the HVR-H1 sequence is SEQ ID NO:23.

### Claim 6 (depends on 1)

The antibody of claim 1, comprising a VH chain having an amino acid sequence selected from SEQ ID NOs: 20 and 21.

### Claim 7 (depends on 6)

The antibody of claim 6, wherein the VH chain amino acid sequence is SEQ ID NO:21.

### Claim 8 (depends on 1)

The antibody of claim 1, wherein the HVR-L1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:8.

### Claim 9 (depends on 1)

The antibody of claim 1, wherein the HVR-L2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO:9 and SEQ ID NO:10.

### Claim 10 (depends on 1)

The antibody of claim 1, wherein the HVR-L3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:11-16.

### Claim 11 (depends on 1)

The antibody of claim 1, comprising an HVR-L1 sequence of SEQ ID NO:7 or SEQ ID NO:8; an HVR-L2 sequence of SEQ ID NO:9 or SEQ ID NO:10; and an HVR-L3 sequence selected from the group consisting of: SEQ ID NOs:11-16.

### Claim 12 (depends on 11)

The antibody of claim 11, wherein the HVR-L1 sequence is SEQ ID NO:7, the HVR-L2 sequence is SEQ ID NO:9 and the HVR-L3 sequence is SEQ ID NO:12.

### Claim 13 (depends on 1)

The antibody of claim 1, comprising a VL chain sequence having an amino acid sequence selected from the group consisting of: SEQ ID NOs: 1-6.

### Claim 14 (depends on 13)

The antibody of claim 13, wherein the VL chain amino acid sequence is SEQ ID NO:2.

### Claim 15 (depends on 5)

The antibody of claim 5, wherein the HVR-L1 comprises the amino acid sequence of SEQ ID NO:7, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:9 and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:12.

### Claim 16 (depends on 14)

The antibody of claim 14, further comprising a VH chain comprising the amino acid sequence of SEQ ID NO:21.

### Claim 17 (depends on 1)

The antibody of claim 1, which is a monoclonal antibody.

### Claim 18 (depends on 1)

The antibody of claim 1, which is a human, humanized, or chimeric antibody.

### Claim 19 (depends on 1)

The antibody of claim 1, which is an antibody fragment.

### Claim 20 (depends on 1)

The antibody of claim 1, which is a full length IgG1 antibody.

### Claim 21 (depends on 1)

An immunoconjugate comprising the antibody of claim 1 and a cytotoxic agent.

### Claim 22 (depends on 1)

A pharmaceutical formulation comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

### Claim 23 (depends on 1)

The antibody of claim 1, wherein the HVR-H1 sequence is SEQ ID NO:22.

### Claim 24 (depends on 23)

The antibody of claim 23, wherein the HVR-L1 sequence is SEQ ID NO:7, the HVR-L2sequence is SEQ ID NO:9 and the HVR-L3 sequence is SEQ ID NO:11.

### Claim 25 (depends on 23)

The antibody of claim 23, wherein the HVR-L1 sequence is SEQ ID NO:7, the HVR-L2 sequence is SEQ ID NO:9 and the HVR-L3 sequence is SEQ ID NO:13.

### Claim 26 (depends on 23)

The antibody of claim 23, wherein the HVR-L1 sequence is SEQ ID NO:7, the HVR-L2 sequence is SEQ ID NO:9 and the HVR-L3 sequence is SEQ ID NO:14.

### Claim 27 (depends on 23)

The antibody of claim 23, wherein the HVR-L1 sequence is SEQ ID NO:8, the HVR-L2 sequence is SEQ ID NO:10 and the HVR-L3 sequence is SEQ ID NO:15.

### Claim 28 (depends on 23)

The antibody of claim 23, wherein the HVR-L1 sequence is SEQ ID NO:7, the HVR-L2 sequence is SEQ ID NO:9 and the HVR-L3 sequence is SEQ ID NO:16.