# US 2019/0170753 A1 · Hcv core and minicore binding molecules

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- Number: US 2019/0170753 A1
- Document ID: US20190170753A1
- Status: Published application
- Kind: A1
- Application number: 16/227,104
- Filed: 2018-12-20
- Published: 2019-06-06
- Earliest claimed: 2016-06-22
- Assignees: Icahn School of Medicine at Mount Sinai
- Applicants: Icahn School of Medicine at Mount Sinai
- Inventors: Andrea BRANCH; Francis ENG
- Web page: https://patentgrep.com/patent/US20190170753A1

## CPC

- G01N 33/5767: {non-A, non-B hepatitis}
- C07K 16/118: Hepatitis C virus; GB virus C [GBV-C]
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- 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]
- G01N 2333/186: Hepatitis C; Hepatitis NANB
- 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)
- 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)

## Abstract

The present disclosure relates to hepatitis C virus (HCV) core and minicore-binding molecules and nucleic acid sequences encoding such molecules. In particular embodiments, the present invention provides HCV core and minicore-binding molecules (e.g., monoclonal antibodies or antibody fragments) with particular light chain and/or heavy chain CDRs (e.g., selected from SEQ ID NOS: 2-4 and 6-8) and methods for using such molecules to detect the presence of HCV core proteins (e.g., mature p21 core protein or minicore proteins) in a sample.

## Claims

### Claim 1

A hepatitis C virus (HCV) core protein-binding molecule, comprising:
a) a light chain variable region comprising
i) a first light chain complementarity determining region (CDRL1) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 2, and SEQ ID NO: 2 with one or more conservative amino acid changes;
ii) a second light chain CDR (CDRL2) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:3 with one or more conservative amino acid changes; and
iii) a third light chain CDR (CDRL3) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:4 with one or more conservative amino acid changes; and
b) a heavy chain variable region, comprising
i) a first heavy chain CDR (CDRH1) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:6 with one or more conservative amino acid changes;
ii) a second heavy chain CDR (CDRH2) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:7 with one or more conservative amino acid changes; and
iii) a third heavy chain CDR (CDRH3) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:8 and SEQ ID NO:8 with one or more conservative amino acid changes.

### Claim 2 (depends on 1)

The HCV core protein-binding molecule of claim 1, wherein said HCV core protein-binding molecule is an antibody or antibody fragment capable of binding HCV p21 core protein and/or HCV 70 or 91 minicore protein.

### Claim 3 (depends on 1)

The HCV core protein-binding molecule of claim 1, wherein said antibody fragment is an Fab or Fv antibody fragment.

### Claim 4 (depends on 1)

The HCV core protein-binding molecule of claim 1, wherein said antibody fragment comprises an antigen binding portion of the Neo4 antibody.

### Claim 5 (depends on 1)

The HCVcore protein-binding molecule of claim 1, wherein said light and/or heavy chain variable region comprises a mouse or human framework region.

### Claim 6 (depends on 1)

The HCV core protein-binding molecule of claim 1, wherein said HCV core protein-binding molecule has a higher binding affinity for p21 core or a minicore protein than monoclonal antibody C11-3 (ABT-4).

### Claim 7 (depends on 1)

The HCV core protein-binding molecule of claim 1, wherein said HCV core protein-binding molecule is capable of binding HCV p21 core protein.

### Claim 8 (depends on 1)

The HCV core protein-binding molecule of claim 1, wherein said HCV core protein-binding molecule is capable of binding HCV 70 or 91 minicore protein.

### Claim 9 (depends on 1)

A composition comprising the HCV core protein-binding molecule of claim 1.

### Claim 10

A nucleic acid comprising:
a) a first nucleic acid sequence encoding a light chain variable region, wherein said light chain variable region comprises
i) a CDRL1 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 2 with one or more conservative amino acid changes;
ii) a CDRL2 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 3 and SEQ ID NO: 3 with one or more conservative amino acid changes; and
iii) a CDRL3 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 4 with one or more conservative amino acid changes; and
b) a second nucleic acid sequence encoding a heavy chain variable region, wherein said heavy chain variable region comprises;
i) a CDRH1 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:6 with one or more conservative amino acid changes;
ii) a CDRH2 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:7 with one or more conservative amino acid changes; and
iii) a CDRH3 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:8 and SEQ ID NO:8 with one or more conservative amino acid changes.

### Claim 11 (depends on 10)

The nucleic acid of claim 10, wherein said light chain variable region comprises a mouse or human framework region.

### Claim 12 (depends on 10)

The nucleic acid of claim 10, wherein said heavy chain variable region comprises a mouse or human framework region.

### Claim 13 (depends on 10)

An expression vector comprising the nucleic acid of claim 10.

### Claim 14 (depends on 10)

A host cell comprising a nucleic acid of claim 10.

### Claim 15 (depends on 1)

A method of detecting an HCV core protein in a sample comprising:
a) contacting a sample suspected of containing an HCV core protein with a HCV core protein-binding molecule of claim 1, wherein said HCV core protein binding molecule forms a complex with said HCV core protein if present in said sample; and
b) detecting the presence or absence of said complex in said sample.

### Claim 16 (depends on 15)

The method of claim 15, wherein said HCV core protein binding molecule comprises a detectable label.

### Claim 17 (depends on 15)

The method of claim 15, wherein said HCV core protein comprises mature p21 core protein.

### Claim 18 (depends on 15)

The method of claim 15, wherein said HCV core protein comprises 70 or 91 minicore protein.

### Claim 19 (depends on 15)

The method of claim 15, further comprising contacting said sample with a conjugate molecule capable of binding to said HCV core protein binding molecule, wherein said conjugate molecule comprises a detectable label.

### Claim 20 (depends on 19)

The method of claim 19, wherein said conjugate molecule comprises an anti-mouse antibody or a conjugate peptide.

### Claim 21 (depends on 15)

The method of claim 15, wherein said HCV core protein binding molecule comprises biotin, and said method further comprises contacting said sample with streptavidin coated paramagnetic microparticles.

### Claim 22 (depends on 15)

The method of claim 15, wherein said conjugate peptide comprises at least 5 consecutive amino acids from the amino acid sequence: SPRGSRPSWGPTDPRRRSRNLGKVI (SEQ ID NO: 36).

### Claim 23 (depends on 15)

The method of claim 15, wherein said detecting comprises adding a chemiluminescent solution to said sample.

### Claim at position 24

24-28. (canceled)

### Claim 29 (depends on 13)

A host cell comprising an expression vector of claim 13.