# US 11,078,273 B2 · ROR2 antibody compositions and related methods

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- Number: US 11,078,273 B2
- Document ID: US11078273B2
- Status: Granted
- Kind: B2
- Application number: 16/071,361
- Filed: 2017-01-20
- Published: 2019-01-31
- Granted: 2021-08-03
- Earliest claimed: 2016-01-20
- Assignees: The Scripps Research Institute
- Applicants: The Scripps Research Institute
- Inventors: Christoph Rader; Haiyong Peng; Xiuling Li
- Web page: https://patentgrep.com/patent/US11078273B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 47/6809: {Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 35/00: Antineoplastic agents
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- 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

The disclosure provides antibodies, antibody fragments or antigen-binding fragments, as well as related antibody drug conjugates (ADCs) and chimeric antigen receptors (CARs), that specifically recognize human ROR2, Also provided in the disclosure are methods of using such antibodies in various diagnostic and therapeutic applications.

## Claims

### Claim 1

An antibody, an antibody-based binding protein or an antibody fragment that specifically binds to the extracellular domain of human receptor tyrosine kinase-like orphan receptor 2 (ROR2), comprising heavy chain CDR1-3 sequences and light chain CDR1-3 sequences that are respectively identical to SEQ ID NOs:25-27 and SEQ ID NOs:61-63.

### Claim 2 (depends on 1)

The antibody, antibody-based binding protein or antibody fragment of claim 1, comprising a heavy chain variable region sequence and a light chain variable region sequence that are at least 95% identical to SEQ ID NO:1 and SEQ ID NO:13, respectively.

### Claim 3 (depends on 1)

The antibody, antibody-based binding protein or antibody fragment of claim 1, comprising a heavy chain variable region sequence and a light chain variable region sequence respectively shown in SEQ ID NO:1 and SEQ ID NO:13.

### Claim 4 (depends on 1)

The antibody, antibody-based binding protein or antibody fragment of claim 1, wherein the antibody or antibody fragment is chimeric or humanized.

### Claim 5 (depends on 1)

The antibody, antibody-based binding protein or antibody fragment of claim 1, wherein the antibody or antibody fragment is IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, synthetic IgG, IgM, F(ab)2, Fv, scFv, IgGACH2, F(ab′)2, scFv2CH3, Fab, VL, VH, scFv4, scFv3, scFv2, dsFv, Fv, scFv-Fc, (scFv)2, a non-depleting IgG, a diabody, or a bivalent antibody.

### Claim 6 (depends on 1)

The antibody, antibody-based binding protein or antibody fragment of claim 1, which is conjugated to a synthetic molecule.

### Claim 7 (depends on 6)

The antibody, antibody-based binding protein or antibody fragment of claim 6, wherein the synthetic molecule is a cytotoxic agent, a label, a therapeutic radioisotope, or a liposome.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising (1) a therapeutically effective amount of an antibody, antibody-based binding protein or antibody fragment of claim 1, and (2) a pharmaceutically acceptable carrier.

### Claim 9 (depends on 1)

A kit comprising the antibody or antigen-binding fragment of claim 1.

### Claim 10

An antibody drug conjugate (ADC), comprising an antibody, an antibody-based binding protein or an antibody fragment that specifically binds to the extracellular domain of human receptor tyrosine kinase-like orphan receptor 2 (ROR2), comprising heavy chain CDR1-3 sequences and light chain CDR1-3 sequences that are respectively identical to SEQ ID NOs:25-27 and SEQ ID NOs:61-63.

### Claim 11 (depends on 10)

The antibody drug conjugate of claim 10, wherein the cytotoxic agent is a small molecular weight toxin, a peptide toxin, or a protein toxin.

### Claim 12 (depends on 10)

The antibody drug conjugate of claim 10, wherein the antibody or antibody fragment comprises a heavy chain variable region sequence and a light chain variable region sequence respectively shown in SEQ ID NO:1 and SEQ ID NO:13.

### Claim 13 (depends on 10)

A pharmaceutical composition comprising (1) a therapeutically effective amount of an antibody drug conjugate (ADC) of claim 10, and (2) a pharmaceutically acceptable carrier.