# US 12,595,307 B2 · Anti-CTLA4 monoclonal antibodies and chimeric antigen receptors

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- Number: US 12,595,307 B2
- Document ID: US12595307B2
- Status: Granted
- Kind: B2
- Application number: 18/001,566
- Filed: 2021-06-09
- Published: 2024-03-14
- Granted: 2026-04-07
- Earliest claimed: 2020-06-11
- Assignees: NantBio, Inc.
- Applicants: NantBio, Inc.
- Inventors: Clifford Anders Olson; Shiho Tanaka; Kayvan Niazi; Melanie Hermreck; Thomas H. King; Zhimin Guo
- Web page: https://patentgrep.com/patent/US12595307B2

## CPC

- C07K 16/2818: {against CD28 or CD152}
- G01N 33/532: Production of labelled immunochemicals
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61P 35/00: Antineoplastic agents
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- G01N 33/575: for cancer
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/35: Valency
- C07K 2317/622: Single chain antibody (scFv)
- 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)
- 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)
- 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

## Abstract

Compositions and methods are presented in which selected polypeptide compounds bind to CTLA-4. Most typically, binding is mediated by selected VH and/or VL domains, and preferred compounds are prepared as scFv, IgG, or CAR.

## Claims

### Claim 1

An antibody or fusion protein comprised thereof, comprising: a variable heavy chain (VH) segment and a variable light chain (VL) segment respectively consisting of SEQ ID NO:60 and SEQ ID NO: 63, SEQ ID NO:61 and SEQ ID NO:63, SEQ ID NO: 62 and SEQ ID NO:63, SEQ ID NO:64 and SEQ ID NO:67, SEQ ID NO:65 and SEQ ID NO:67, SEQ ID NO:66 and SEQ ID NO:67, SEQ ID NO: 68 and SEQ ID NO:69, or SEQ ID NO:70 and SEQ ID NO:71.

### Claim 2 (depends on 1)

The antibody of claim 1 comprising a variable heavy chain (VH) segment and a variable light chain (VL) segment respectively consisting of SEQ ID NO:60 and SEQ ID NO: 63, SEQ ID NO:61 and SEQ ID NO:63, SEQ ID NO:62 and SEQ ID NO:63, SEQ ID NO:64 and SEQ ID NO:67, SEQ ID NO:65 and SEQ ID NO:67, SEQ ID NO:66 and SEQ ID NO:67, SEQ ID NO: 68 and SEQ ID NO:69, or SEQ ID NO:70 and SEQ ID NO:71.

### Claim 3

An antibody, comprising a heavy chain comprising a first amino acid sequence of SEQ ID NO. 68 and a light chain comprising a second amino acid sequence of SEQ ID NO. 69, or a heavy chain comprising a first amino acid sequence of SEQ ID NO. 70 and a light chain comprising a second amino acid sequence of SEQ ID NO. 71.

### Claim 4

A recombinant nucleic acid, comprising: a first nucleic acid segment encoding a variable heavy chain (VH) peptide sequence and second nucleic acid segment encoding a variable light chain (VL) peptide sequence, wherein the VH and VL peptide sequences combine to form an antibody, scfv, or fusion proteins derived therefrom, and wherein the VH and VL peptides respectively consist of SEQ ID NO:60 and SEQ ID NO:63, SEQ ID NO:61 and SEQ ID NO:63, SEQ ID NO:62 and SEQ ID NO:63, SEQ ID NO: 64 and SEQ ID NO:67, SEQ ID NO: 65 and SEQ ID NO:67, SEQ ID NO: 66 and SEQ ID NO:67, SEQ ID NO: 68 and SEQ ID NO:69, or SEQ ID NO: 70 and SEQ ID NO:71; and wherein the first and second segments are optionally in a bicistronic arrangement.

### Claim 5

A recombinant nucleic acid, comprising: a first nucleic acid segment encoding a first amino acid sequence of SEQ ID NO. 68 and second nucleic acid segment encoding a second amino acid sequence of SEQ ID NO. 69, or a first nucleic acid segment encoding a first amino acid sequence of SEQ ID NO. 70 and a second nucleic acid segment encoding a second amino acid sequence of SEQ ID NO. 71.

### Claim 6 (depends on 4)

The recombinant nucleic acid of claim 4 further comprising a third segment encoding a polypeptide that encodes at least a portion of a N-803 or TxM, wherein the N-803 or TxM, when expressed in the cell, has an antigen binding domain that comprises an scfv peptide encoded by the first and second nucleic acid segment.

### Claim 7 (depends on 1, 2, 3)

A method of reducing immune suppression in a patient having a tumor, comprising: administering to the patient a pharmaceutical composition including an antibody or fusion protein of any one of claims 1-3; and wherein the pharmaceutical composition is administered to the patient in a dose and a schedule effective to reduce immune suppression in a tumor microenvironment.

### Claim 8 (depends on 1, 2, 3)

A method of using an antibody or fusion protein of any one of claims 1-3 for treating a cancer and/or reducing immune suppression in a patient having a tumor, comprising: administering to the patient the antibody or fusion protein at a dose and schedule effective to treat the tumor and/or reduce immune suppression in a tumor microenvironment.
