# US 2022/0033504 A1 · Antibodies targeting a complex comprising non-classical hla-i and neoantigen and their methods of use

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- Number: US 2022/0033504 A1
- Document ID: US20220033504A1
- Status: Published application
- Kind: A1
- Application number: 17/199,258
- Filed: 2021-03-11
- Published: 2022-02-03
- Earliest claimed: 2020-06-01
- Assignees: Abexxa Biologics, Inc.
- Applicants: AbeXXa Biologics, Inc.
- Inventors: Jon Weidanz; Katherine Upchurch-Ange
- Web page: https://patentgrep.com/patent/US20220033504A1

## CPC

- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- A61P 35/00: Antineoplastic agents
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/50: characterized by immunoglobulin fragments
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/62: comprising only variable region components
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/64: comprising a combination of variable region and constant region components
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C07K 2319/00: Fusion polypeptide
- 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

## Abstract

Provided herein are antibodies that selectively bind to complex comprising a non-classical HLA-I (e.g. HLA-E) and a neoantigen having variable heavy chain domains (VH), variable light chain domains (VL), and complementarity determining regions (CDRs) as disclosed herein, as well as methods and uses thereof.

## Claims

### Claim at position 1

-229. (canceled)

### Claim 230

A monoclonal antibody, or an antigen-binding fragment thereof, that selectively binds to a complex comprising an HLA-E and a peptide comprising the sequence according to SEQ ID NO: 18 (VMAPRTLFL), said antibody or antigen-binding fragment thereof comprising:
(i) a light chain variable domain (VL) comprising an amino acid sequence at least 90% identical to the sequence of SEQ ID NO: 7, wherein the VL amino acid sequence comprises a CDR1 having the amino acid sequence set forth as SEQ ID NO: 1, a CDR2 having the amino acid sequence set forth as SEQ ID NO: 2, and a CDR3 having the amino acid sequence set forth as SEQ ID NO: 3; and
(ii) a heavy chain variable domain (VH) comprising an amino acid sequence at least 90% identical to the sequence of SEQ ID NO: 8, wherein the VH amino acid sequence comprises a CDR1 having the amino acid sequence set forth as SEQ ID NO: 4, a CDR2 having the amino acid sequence set forth as SEQ ID NO: 5, and a CDR3 having the amino acid sequence set forth as SEQ ID NO: 6.

### Claim 231 (depends on 230)

The monoclonal antibody of claim 230, wherein the VL comprises the amino acid sequence of SEQ ID NO: 7 and the VH comprises the amino acid sequence of SEQ ID NO: 8.

### Claim 232 (depends on 230)

The monoclonal antibody of claim 230, wherein the monoclonal antibody or antigen-binding fragment thereof does not have a binding affinity to (i) the HLA-E alone; or (ii) the peptide alone.

### Claim 233 (depends on 230)

A pharmaceutical composition, comprising (a) the monoclonal antibody or antigen-binding fragment thereof of claim 230; and (b) a pharmaceutically acceptable excipient.

### Claim 234 (depends on 230)

A bispecific T cell engager, comprising the monoclonal antibody or antigen binding-fragment thereof of claim 230.

### Claim 235 (depends on 233)

The bispecific T cell engager of claim 233, wherein the bispecific T cell engager binds to a CD3 protein associated with a T cell receptor.

### Claim 236 (depends on 234)

A pharmaceutical composition, comprising (a) the bispecific T cell engager of claim 234; and (b) a pharmaceutically acceptable excipient.

### Claim 237 (depends on 230)

A method of treating a cancer that expresses both HLA-E and HLA-G in an individual in need thereof, comprising administering to the individual an effective amount of the monoclonal antibody or antigen-binding fragment thereof of claim 230, to thereby treat the cancer.

### Claim 238 (depends on 237)

The method of claim 237, wherein the cancer is breast cancer, kidney cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, choriocarcinoma, non-small cell lung carcinoma (NSCLC), gastric cancer, cervical cancer, head and neck cancer, leukemia, lymphoma, myeloma, multiple myeloma (MM), acute myeloid leukemia (AML), myelodysplastic syndrome, a B-cell malignancy, or mantel cell lymphoma.

### Claim 239 (depends on 234)

A method of treating a cancer that expresses both HLA-E and HLA-G in an individual in need thereof, comprising administering to the individual an effective amount of the bispecific T cell engager of claim 234, to thereby treat the cancer.

### Claim 240 (depends on 239)

The method of claim 239, wherein the cancer is breast cancer, kidney cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, choriocarcinoma, non-small cell lung carcinoma (NSCLC), gastric cancer, cervical cancer, head and neck cancer, leukemia, lymphoma, myeloma, multiple myeloma (MM), acute myeloid leukemia (AML), myelodysplastic syndrome, a B-cell malignancy, or mantel cell lymphoma.