# US 9,750,804 B2 · Alpha-enolase specific antibodies and method of use in immune diseases

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- Number: US 9,750,804 B2
- Document ID: US9750804B2
- Status: Granted
- Kind: B2
- Application number: 14/580,127
- Filed: 2014-12-22
- Published: 2015-06-25
- Granted: 2017-09-05
- Earliest claimed: 2013-12-20
- Assignees: Development Center for Biotechnology; National Health Research Institutes
- Applicants: Development Center for Biotechnology; National Health Research Institutes
- Inventors: Shih-Chong Tsai; Mingl Chang; Ta-Tung Yuan; Shih-Chi Tseng; Shyi-Jou Chen; Wei-Tso Chia; Hsin-Yun Wang; Neng-Yao Shih; Ko-Jiunn Liu; Li-Tzong Chen
- Web page: https://patentgrep.com/patent/US9750804B2

## CPC

- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- B63B 1/121: {comprising two hulls (B63B1/107 takes precedence)}
- B63B 15/02: Staying of masts or of other superstructures
- B63H 9/08: Connections of sails to masts, spars, or the like
- C07K 16/40: against enzymes
- A61K 2039/505: {comprising antibodies}
- B63B 2001/123: {interconnected by a plurality of beams, or the like members only}
- B63B 2015/005: {with means for varying mast position or orientation with respect to the hull}
- 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 2317/76: 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
- 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
- B63B: SHIPS OR OTHER WATERBORNE VESSELS; EQUIPMENT FOR SHIPPING (arrangements of vessel ventilation, heating, cooling, or air-conditioning B63J2/00; floating substructures as supports of dredgers or soil-shifting machines E02F9/06)
- B63H: MARINE PROPULSION OR STEERING (propulsion of air-cushion vehicles B60V1/14; specially adapted for submarines, other than nuclear propulsion, B63G; specially adapted for torpedoes F42B19/00)
- 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

A method for treating an inflammatory disease or an immune disorder includes administering to a subject in need of such treatment an antagonist against ENO1. The antagonist binds ENO1 and inhibits ENO1 plasminogen receptor activity. The antagonist may be an anti-human ENO1 antibody, or an scFv, Fab, or F(ab)2 fragment thereof, that specifically binds to human ENO1 (GenBank: AAH50642.1) for the treatment of an inflammatory disease or an immune disorder, which may be multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, systemic Lupus erythematosus, chronic obstructive pulmonary disease (COPD), asthma, allergy, psoriasis, type 1 diabetes mellitus, artherosclerosis or osteoporosis.

## Claims

### Claim 1

An antibody, or an scFv, Fab or F(ab)2 fragment thereof, wherein the antibody, or the scFv or Fab or F(ab)2 fragment thereof, can bind to an epitope on human ENO1 and inhibit ENO1 plasminogen receptor activity, wherein the epitope is located in a region consisting of the sequence of 296FDQDDWGAWQKFTASAGIQVVGDDLTVTNPK RIAKAVNEKS336 (SEQ ID NO:39) of human ENO1.

### Claim 2 (depends on 1)

The antibody, or an scFv, Fab or F(ab)2 fragment thereof, according to claim 1, wherein the epitope is located in a region consisting of the sequence of 296FDQDDWGAWQKFTA 309 (SEQ ID NO:40) or 326KRIAKAVNEKS336 (SEQ ID NO:41) of human ENO1.

### Claim 3 (depends on 1)

The antibody, or the scFv, Fab or F(ab)2 fragment thereof, according to claim 1, wherein the antibody is a monoclonal antibody.

### Claim 4 (depends on 1)

A pharmaceutical composition for treating an inflammatory disease or an immune disorder, comprising the antibody, or the scFv, Fab or F(ab)2 fragment thereof, according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 5 (depends on 1)

A method for treating an inflammatory disease or an immune disorder, comprising administering to a subject in need thereof the antibody, or an scFv, Fab or F(ab)2 fragment thereof, according to claim 1 an antagonist against ENO1, wherein the antagonist binds ENO1 and inhibits ENO1 plasminogen receptor activity.

### Claim 6 (depends on 5)

The method of claim 5, wherein the subject is human and the anti-ENO1 antibody binds human ENO1 protein.

### Claim 7 (depends on 6)

The method of claim 6, wherein the anti-ENO1 antibody inhibits a plasminogen receptor activity of the human ENO1 protein by preventing plasminogen from binding to the human ENO1 protein.

### Claim 8 (depends on 5)

The method of claim 5, wherein the anti-ENO1 antibody is a monoclonal antibody.

### Claim 9 (depends on 5)

The method of claim 5, wherein the inflammatory disease or immune disorder is multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, systemic Lupus erythematosus, chronic obstructive pulmonary disease (COPD), asthma, allergy, psoriasis, type 1 diabetes mellitus, atherosclerosis or osteoporosis.

### Claim 10 (depends on 9)

The method of claim 9, wherein the anti-ENO1 antibody is a monoclonal antibody.

### Claim 11 (depends on 10)

The method of claim 10, wherein the anti-ENO1 antibody binds human ENO1 with a Kd of 1×10-7M or less.

### Claim 12 (depends on 5)

The method of claim 5, wherein the anti-ENO1 antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, an affinity matured antibody, a human antibody, a bispecific antibody and antibody drug conjugated (ADC).

### Claim 13 (depends on 5)

The method of claim 5, wherein the anti-ENO1 antibody can specifically bind to an ENO1 plasminogen receptor of monocytes or leukocytes.

### Claim 14 (depends on 5)

The method of claim 5, further comprising administering to the subject in need thereof an immune-suppressor immune-suppression modulator.

### Claim 15 (depends on 5)

The method according to claim 5, wherein the epitope is located in a region consisting of the sequence of 296FDQDDWGAWQKFTA309 (SEQ ID NO:40) or 326KRIAKAVNEKS336 (SEQ ID NO:41) of human ENO1.