# US 11,078,260 B2 · Antibodies to endoplasmin and their use

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- Number: US 11,078,260 B2
- Document ID: US11078260B2
- Status: Granted
- Kind: B2
- Application number: 15/870,532
- Filed: 2018-01-12
- Published: 2018-08-16
- Granted: 2021-08-03
- Earliest claimed: 2010-06-16
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of The Commonwealth System of Higher Education
- Inventors: Soldano Ferrone; Xinhui Wang; Thomas P. Conrads; Elvira Favoino; Brian L. Hood
- Web page: https://patentgrep.com/patent/US11078260B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 47/6843: {the antibody targeting a material from animals or humans}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 39/04: Chelating agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/30: from tumour cells
- C07K 16/3015: {Breast}
- C07K 16/3023: {Lung}
- C07K 16/303: {Liver or Pancreas}
- C07K 16/3038: {Kidney, bladder}
- C07K 16/3053: {Skin, nerves, brain}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 16/3092: {against tumour-associated mucins}
- G01N 33/575: for cancer
- G01N 33/577: involving monoclonal antibodies {binding reaction mechanisms characterised by the use of monoclonal antibodies (G01N33/5302 - G01N33/576 take precedence)}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- C07K 2317/21: from primates, e.g. man
- 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 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/624: Disulfide-stabilized antibody (dsFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2319/55: containing a fusion with a toxin, e.g. diphteria toxin
- C07K 2319/60: containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 15/09: Recombinant DNA-technology
- C12N 15/62: DNA sequences coding for fusion proteins
- C12N 15/8258: {for the production of oral vaccines (antigens) or immunoglobulins}
- C12N 15/86: Viral vectors
- C12N 2800/00: Nucleic acids vectors
- C12N 2810/859: from immunoglobulins
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2333/4727: Calcium binding proteins, e.g. calmodulin
- G01N 2800/7028: Cancer
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Isolated monoclonal antibodies are disclosed herein that specifically bind endoplasmin. In some embodiments these antibodies are fully human. Recombinant nucleic acids encoding these antibodies, expression vectors including these nucleic acids, and host cells transformed with these expression vectors are also disclosed herein. In several embodiments the disclosed antibodies are of use for detecting and/or treating tumors that express endoplasmin, such as melanoma, breast cancer, head and neck squamous cell carcinoma, renal cancer, lung cancer, glioma, bladder cancer, ovarian cancer or pancreatic cancer. In one example, the tumor is a melanoma.

## Claims

### Claim 1

An isolated chimeric molecule comprising a human monoclonal antibody, or antigen binding fragment thereof, linked to an interferon,
wherein the human monoclonal antibody or the antigen binding fragment thereof comprises a heavy chain variable domain and a light chain variable domain, and wherein:
a) the heavy chain variable domain comprises amino acids 26-33 of SEQ ID NO: 1, amino acids 51-58 of SEQ ID NO: 1, and amino acids 97-103 of SEQ ID NO: 1;
b) the light chain variable domain comprises amino acids 27-32 of SEQ ID NO: 2, amino acids 50-52 of SEQ ID NO: 2, and amino acids 89-97 of SEQ ID NO: 2; and
c) the human monoclonal antibody or the antigen binding fragment thereof specifically binds human endoplasmin.

### Claim 2 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the interferon (IFN) is IFN-α, IFN-β, or IFN-γ.

### Claim 3 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the heavy chain variable domain of the antibody comprises SEQ ID NO: 1.

### Claim 4 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the light chain variable domain of the antibody comprises SEQ ID NO: 2.

### Claim 5 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the antigen-binding fragment is a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a single chain Fv protein (scFv), or a disulfide stabilized Fv protein (dsFv).

### Claim 6 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the human monoclonal antibody is an IgG.

### Claim 7 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the antibody or the antigen binding fragment thereof is labeled.

### Claim 8 (depends on 1)

A composition comprising the isolated chimeric molecule of claim 1, and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 1)

The isolated chimeric molecule of claim 1, wherein the IFN is IFN-α.

### Claim 10 (depends on 9)

The isolated chimeric molecule of claim 9, wherein the heavy chain variable domain comprises SEQ ID NO: 1.

### Claim 11 (depends on 9)

The isolated chimeric molecule of claim 9, wherein the light chain variable domain comprises SEQ ID NO: 2.

### Claim 12 (depends on 9)

The isolated chimeric molecule of claim 9, wherein the antigen-binding fragment is a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a single chain Fv protein (scFv), or a disulfide stabilized Fv protein (dsFv).

### Claim 13 (depends on 9)

The isolated chimeric molecule of claim 9, wherein the human monoclonal antibody is an IgG.

### Claim 14 (depends on 9)

The isolated chimeric molecule of claim 9, wherein the human monoclonal antibody or the antigen binding fragment thereof is labeled.

### Claim 15 (depends on 9)

A composition comprising the isolated chimeric molecule of claim 9, and a pharmaceutically acceptable carrier.