# US 12,222,355 B2 · Therapeutic antibodies against ROR-1 protein and methods for use of same

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- Number: US 12,222,355 B2
- Document ID: US12222355B2
- Status: Granted
- Kind: B2
- Application number: 18/058,239
- Filed: 2022-11-22
- Published: 2023-10-26
- Granted: 2025-02-11
- Earliest claimed: 2011-01-14
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Thomas J. Kipps; George F. Widhopf, II; Bing Cui
- Web page: https://patentgrep.com/patent/US12222355B2

## CPC

- G01N 33/6854: {Immunoglobulins}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/40: against enzymes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

Therapeutic antibodies having binding specificity for ROR-1 expressed on cancer cells (particularly leukemic and lymphomic cells) and pharmaceutical compositions containing one or more such antibodies for use in treating cancer. Methods for diagnosing such cancers through in vitro detection of binding to ROR-1 protein expressed on putative cancer cells are also provided.

## Claims

### Claim 1

An isolated anti-ROR1 antibody comprising a humanized heavy chain variable region and a humanized light chain variable region, wherein:
a) said heavy chain variable region comprises complementarity determining regions corresponding to amino acids 26 to 33, 51 to 57, and 96 to 106 of SEQ ID NO: 14, and said light chain variable region comprises complementarity determining regions corresponding to amino acids 26 to 31, 49 to 51, and 88 to 96 of SEQ ID NO: 16;
b) said heavy chain variable region comprises complementarity determining regions corresponding to amino acids 26 to 33, 51 to 58, and 97 to 108 of SEQ ID NO: 6, and said light chain variable region comprises complementarity determining regions corresponding to amino acids 27 to 32, 50 to 52, and 89 to 97 of SEQ ID NO: 8; or
c) said heavy chain variable region comprises complementarity determining regions corresponding to amino acids 26 to 33, 51 to 57, and 96 to 107 of SEQ ID NO: 18, and said light chain variable region comprises complementarity determining regions corresponding to amino acids 27 to 32, 50 to 52, and 89 to 97 of SEQ ID NO: 20.

### Claim 2 (depends on 1)

The isolated anti-ROR1 antibody of claim 1, wherein said heavy chain variable region comprises an amino acid sequence at least 90% identical to that set forth in SEQ ID NO: 14, and said light chain variable region comprises an amino acid sequence at least 90% identical to that set forth in SEQ ID NO: 16.

### Claim 3 (depends on 1)

The isolated anti-ROR1 antibody of claim 1, wherein said heavy chain variable region comprises an amino acid sequence at least 90% identical to that set forth in SEQ ID NO: 6, and wherein said light chain variable region comprises an amino acid sequence at least 90% identical to that set forth in SEQ ID NO: 8.

### Claim 4 (depends on 1)

The isolated anti-ROR1 antibody of claim 1, wherein said heavy chain variable region comprises an amino acid sequence at least 90% identical to that set forth in SEQ ID NO: 18, and said light chain variable region comprises an amino acid sequence at least 90% identical to that set forth in SEQ ID NO: 20.

### Claim 5 (depends on 1)

The isolated anti-ROR1 antibody of claim 1, wherein said anti-ROR1 antibody is a Fab or F (ab′) 2 fragment.

### Claim 6 (depends on 1)

The isolated anti-ROR1 antibody of claim 1, wherein said isolated anti-ROR1 antibody binds residues of ROR1 from position 1 to 147 of SEQ ID NO: 36.

### Claim 7 (depends on 6)

The isolated anti-ROR1 antibody of claim 6, wherein said isolated anti-ROR1 antibody binds a glutamic acid residue corresponding to a glutamic acid residue in the extracellular domain of human ROR-1 protein at position 138 of SEQ ID NO: 36.

### Claim 8 (depends on 1)

The isolated anti-ROR1 antibody of claim 1, wherein said isolated anti-ROR1 antibody further inhibits CD5dullB220+ and ROR1brightB220+ leukemic B cell expansion or proliferation.

### Claim 9 (depends on 1)

A pharmaceutically acceptable composition comprising at least one isolated anti-ROR1 antibody of claim 1 and a pharmaceutically acceptable carrier.