# US 2021/0277130 A1 · Methods of Treating Conditions with Antibodies that Bind Colony Stimulating Factor 1 Receptor (CSF1R)

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- Number: US 2021/0277130 A1
- Document ID: US20210277130A1
- Status: Published application
- Kind: A1
- Application number: 17/173,886
- Filed: 2021-02-11
- Published: 2021-09-09
- Earliest claimed: 2012-05-11
- Assignees: Five Prime Therapeutics, Inc.
- Applicants: Five Prime Therapeutics, Inc.
- Inventors: Brian Wong; Emma Masteller; Justin Wong; Haishan Lin
- Web page: https://patentgrep.com/patent/US20210277130A1

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)}
- 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 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- 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)
- 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

Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (CSF1R) are provided. Such methods include, but are not limited to, methods of treating rheumatoid arthritis and associated conditions, methods of treating systemic lupus erythematosus and associated conditions, and methods of treating multiple sclerosis.

## Claims

### Claim at position 1

-38. (canceled)

### Claim 39

A method of reducing the number of CD16+ monocytes in a subject with a CD16+ disorder, comprising (a) determining the number of CD16+ monocytes in a peripheral blood sample obtained from the subject, and (b) administering to the subject an antibody that binds human colony stimulating factor 1 receptor (CSF1R) such that the number of CD16+ monocytes is reduced by at least 30%; wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to human CSF1R and blocks binding of human IL-34 to human CSF1R, and (ii) comprises a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20.

### Claim 40 (depends on 39)

The method of claim 39, further comprising determining the number of CD16-monocytes in the sample, wherein the antibody is administered such that the number of CD16− monocytes is not reduced or is reduced by less than 20%.

### Claim 41 (depends on 39)

The method of claim 39, further comprising (c) determining the number of CD16+ monocytes in a further peripheral blood sample from the subject after administration of the antibody.

### Claim 42 (depends on 41)

The method of claim 41, further comprising determining the number of CD16-monocytes in the samples of (a) and (c).

### Claim 43 (depends on 39)

The method of claim 39, wherein the method further comprises administering at least one additional therapeutic agent selected from an anti-CD-20 antibody, an anti-CD19 antibody, an anti-GM-CSF antibody, a CTLA-4 antagonist, and an anti-GM-CSF-R antibody.

### Claim 44 (depends on 39)

The method of claim 39, comprising administering to the subject the antibody that binds CSF1R such that the number of CD16+ monocytes is reduced by at least 50%.

### Claim 45 (depends on 39)

The method of claim 39, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46.

### Claim 46 (depends on 39)

The method of claim 39, wherein the antibody is a humanized antibody.

### Claim 47 (depends on 39)

The method of claim 39, wherein the antibody is a Fab, an Fv, an scFv, a Fab′, or a (Fab′)2.

### Claim 48

A method of reducing the number of CD16+ monocytes in a subject with a CD16+ disorder, comprising (a) administering to the subject an antibody that binds human colony stimulating factor 1 receptor (CSF1R), (b) determining the number of CD16+ monocytes in a peripheral blood sample obtained from the subject following administration of the antibody, (c) determining whether administration of the antibody reduces the number of CD16+ monocytes in the sample by at least 30% by comparing the number of CD16+ monocytes in the sample of (b) with the number of CD16+ monocytes determined in a peripheral blood sample obtained from the subject prior to administration, and optionally (d) adjusting the dose or frequency of the administration of the antibody such that the number of CD16+ monocytes remains reduced; wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to human CSF1R and blocks binding of human IL-34 to human CSF1R and (ii) comprises a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20.

### Claim 49 (depends on 48)

The method of claim 48, comprising adjusting the dose or frequency of the administration of the antibody such that the number of CD16+ monocytes remains reduced by at least 30%.

### Claim 50 (depends on 48)

The method of claim 48, further comprising determining the number of CD16-monocytes in the sample after administration, wherein the antibody is administered such that the number of CD16− monocytes is not reduced or is reduced by less than 20%.

### Claim 51 (depends on 48)

The method of claim 48, wherein the method further comprises administering at least one additional therapeutic agent selected from an anti-CD-20 antibody, an anti-CD19 antibody, an anti-GM-CSF antibody, a CTLA-4 antagonist, and an anti-GM-CSF-R antibody.

### Claim 52 (depends on 48)

The method of claim 48, comprising determining whether administration of the antibody reduces the number of CD16+ monocytes in the sample by at least 50%, and optionally adjusting the dose or frequency of the administration of the antibody such that the number of CD16+ monocytes remains reduced by at least 50%.

### Claim 53 (depends on 48)

The method of claim 48, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46.

### Claim 54 (depends on 48)

The method of claim 48, wherein the antibody is a humanized antibody.

### Claim 55 (depends on 48)

The method of claim 48, wherein the antibody is a Fab, an Fv, an scFv, a Fab′, or a (Fab′)2.

### Claim 56

A method of treating neoplasia in a subject, comprising (a) determining the number of CD16+ monocytes in a peripheral blood sample obtained from the subject, and (b) administering to the subject an antibody that binds human colony stimulating factor 1 receptor (CSF1R) such that the number of CD16+ monocytes is reduced by at least 30%; wherein the antibody (i) blocks binding of human colony stimulating factor 1 (CSF1) to human CSF1R and blocks binding of human IL-34 to human CSF1R, and (ii) comprises a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 15, an HC CDR2 having the sequence of SEQ ID NO: 16, and an HC CDR3 having the sequence of SEQ ID NO: 17, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 18, a LC CDR2 having the sequence of SEQ ID NO: 19, and a LC CDR3 having the sequence of SEQ ID NO: 20.

### Claim 57 (depends on 56)

The method of claim 56, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 39 and a light chain comprising the sequence of SEQ ID NO: 46.

### Claim 58 (depends on 56)

The method of claim 56, further comprising (c) determining the number of CD16+ monocytes in a further peripheral blood sample from the subject after administration of the antibody.