# US 12,180,278 B2 · Antibody targeting CD22 and CD79B

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- Number: US 12,180,278 B2
- Document ID: US12180278B2
- Status: Granted
- Kind: B2
- Application number: 17/702,042
- Filed: 2022-03-23
- Published: 2022-09-29
- Granted: 2024-12-31
- Earliest claimed: 2021-03-24
- Assignees: Janssen Biotech, Inc.
- Applicants: Janssen Biotech, Inc.
- Inventors: Kyle J. Bednar; Naresh Kumar; Sanjaya Singh; Danlin Yang; Rajkumar Ganesan
- Web page: https://patentgrep.com/patent/US12180278B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2887: {against CD20}
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/31: multispecific
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/71: Decreased effector function due to an Fc-modification
- 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

Provided herein are multispecific antibodies, that bind to CD79b and CD22, polynucleotides encoding them, vectors, host cells, methods of making and using them.

## Claims

### Claim 1

A bispecific antibody or bispecific binding fragment comprising:
a) a first antigen-binding arm that binds cluster of differentiation 79B protein (CD79B), comprising a first variable heavy domain (VH1) and further comprising a first variable light domain (VL1); and
b) a second antigen-binding arm that binds cluster of differentiation 22 (CD22), comprising a second variable heavy domain (VH2) and further comprising a second variable light domain (VL2), wherein the second antigen-binding arm that binds CD22 comprises at least one selected from the group consisting of:
(i) a VH2 comprising the HCDR1 of SEQ ID NO: 1, the HCDR2 of SEQ ID NO: 2, and the HCDR3 of SEQ ID NO:3, and a VL2 comprising the LCDR1 of SEQ ID NO: 4, the LCDR2 of SEQ ID NO:5, and the LCDR3 of SEQ ID NO:6; and
(ii) the VH2 comprises SEQ ID NO:7 and the VL2 comprises SEQ ID NO: 8.

### Claim 2 (depends on 1)

The bispecific antibody or bispecific binding fragment of claim 1, wherein the first antigen-binding arm that binds CD79b comprises a VH and VL selected from the group consisting of:
a) the VH1 comprises the HCDR1 of SEQ ID NO:9, the HCDR2 of SEQ ID NO: 10, and the HCDR3 of SEQ ID NO: 11; and the VL1 comprises the LCDR1 of SEQ ID NO: 12, the LCDR2 of SEQ ID NO: 13, and the LCDR3 of SEQ ID NO: 14;
b) the VH1 comprises the HCDR1 of SEQ ID NO: 17, the HCDR2 of SEQ ID NO: 18, and the HCDR3 of SEQ ID NO: 19; and the VL1 comprises the LCDR1 of SEQ ID NO:20, the LCDR2 of SEQ ID NO:21, and the LCDR3 of SEQ ID NO:22;
c) the VH1 comprises the HCDR1 of SEQ ID NO:25, the HCDR2 of SEQ ID NO:26, and the HCDR3 of SEQ ID NO:27; and the VL1 comprises the LCDR1 of SEQ ID NO:28, the LCDR2 of SEQ ID NO:29, and the LCDR3 of SEQ ID NO:30;
d) the VH1 comprises the HCDR1 of SEQ ID NO:33, the HCDR2 of SEQ ID NO:34, and the HCDR3 of SEQ ID NO:35; and the VL1 comprises the LCDR1 of SEQ ID NO:36, the LCDR2 of SEQ ID NO:37, and the LCDR3 of SEQ ID NO:38;
e) the VH1 comprises the HCDR1 of SEQ ID NO:41, the HCDR2 of SEQ ID NO:42, and the HCDR3 of SEQ ID NO:43; and the VL1 comprises the LCDR1 of SEQ ID NO:44, the LCDR2 of SEQ ID NO:45, and the LCDR3 of SEQ ID NO:46;
f) the VH1 comprises the HCDR1 of SEQ ID NO:49, the HCDR2 of SEQ ID NO:50, and the HCDR3 of SEQ ID NO:51; and the VL1 comprises the LCDR1 of SEQ ID NO:52, the LCDR2 of SEQ ID NO:53, and the LCDR3 of SEQ ID NO:54; and
g) the VH1 comprises the HCDR1 of SEQ ID NO:57, the HCDR2 of SEQ ID NO:58, and the HCDR3 of SEQ ID NO:59; and the VL1 comprises the LCDR1 of SEQ ID NO:60, the LCDR2 of SEQ ID NO:61, and the LCDR3 of SEQ ID NO:62.

### Claim 3 (depends on 1)

The bispecific antibody or bispecific binding fragment of claim 1, wherein the first antigen-binding arm that binds CD79b comprises a VH and VL selected from the group consisting of:
a) the VH of SEQ ID NO: 15 and the VL of SEQ ID NO: 16;
b) the VH of SEQ ID NO: 23 and the VL of SEQ ID NO: 24;
c) the VH of SEQ ID NO: 31 and the VL of SEQ ID NO: 32;
d) the VH of SEQ ID NO: 39 and the VL of SEQ ID NO: 40;
e) the VH of SEQ ID NO: 47 and the VL of SEQ ID NO: 48;
f) the VH of SEQ ID NO: 55 and the VL of SEQ ID NO: 56;
g) the VH of SEQ ID NO: 63 and the VL of SEQ ID NO: 64; and
h) the VH of SEQ ID NO: 80 and the VL of SEQ ID NO: 81.

### Claim 4 (depends on 1)

The bispecific antibody or bispecific binding fragment of claim 1, wherein the first antigen-binding arm that binds CD79b comprises at least one selected from the group consisting of:
a) a VH1 comprising the HCDR1 of SEQ ID NO:9, the HCDR2 of SEQ ID NO: 10, and the HCDR3 of SEQ ID NO: 11; and a VL1 comprising the LCDR1 of SEQ ID NO: 12, the LCDR2 of SEQ ID NO: 13, and the LCDR3 of SEQ ID NO: 14; and
b) the VH1 comprises SEQ ID NO: 80 and the VL1 comprises SEQ ID NO: 81.

### Claim 5 (depends on 1)

The bispecific antibody or bispecific binding fragment of claim 1, wherein each of the first antigen-binding arm and the second binding arm comprises at least one selected from the group consisting of a single-chain variable fragment (scFv), an (scFv)2, an antigen-binding fragment (Fab), a F (ab′)2, a Fd, a Fv, a VHH, and a dAB.

### Claim 6 (depends on 5)

The bispecific antibody or bispecific binding fragment of claim 5, wherein the first antigen-binding arm comprises an scFv, and the second antigen-binding arm comprises a Fab.

### Claim 7 (depends on 6)

The bispecific antibody or bispecific binding fragment of claim 6, wherein the first antigen-binding arm comprises an scFv having the amino acid sequence of SEQ ID NO:82.

### Claim 8 (depends on 1)

The bispecific antibody or bispecific binding fragment of claim 1, wherein the first antigen-binding arm that binds CD79b comprises a first Fragment crystallizable (Fc) domain, and wherein the second antigen-binding arm that binds CD22 comprises a second Fc domain, wherein at least one of the first and second Fc domain comprises one or more mutations that promote heterodimerization of the Fc domains, reduce Fc binding to a Fcγ receptor, reduce Fc binding to protein A, extend the half-life of the multispecific antibody or multispecific binding fragment, or any combination thereof.

### Claim 9 (depends on 8)

The bispecific antibody or bispecific binding fragment of claim 8, wherein at least one of the first and second Fc domain comprises one or more mutations selected from the group consisting of:
a) one or more mutations that promote heterodimerization of the Fc domains selected from the group consisting of T366S, L368A, T366W, and Y407V (EU numbering);
b) one or more mutations that reduce Fc binding to a Fcγ receptor selected from the group consisting of L234A, L235A, and D265S according to EU numbering;
c) one or more mutations that reduce Fc binding to protein A selected from the group consisting of H435R and Y436F according to EU numbering;
d) one or more mutations that extend the half-life of the bispecific antibody or bispecific binding fragment selected from the group consisting of M252Y, S254T, and T256E according to EU numbering.

### Claim 10 (depends on 9)

The bispecific antibody or bispecific binding fragment of claim 9, wherein at least one of the first and second Fc domain comprises one or more mutations selected from the group consisting of:
a) one or more mutations that promote heterodimerization of the Fc domains wherein the first Fc domain comprise mutation T366W, and wherein the second Fc domain comprises mutations T366S, L368A, and Y407V;
b) one or more mutations that reduce Fc binding to a Fcγ receptor, wherein both the first Fc domain and the second Fc domain comprise mutations L234A, L235A, and D265S;
c) one or more mutations that reduce Fc binding to protein A, wherein the second Fc domain comprises mutations H435R and Y436F;
d) one or more mutations that extend the half-life of the bispecific antibody or bispecific binding fragment wherein both the first Fc domain and the second Fc domain comprise mutations M252Y, S254T, and T256E.

### Claim 11 (depends on 10)

The bispecific antibody or bispecific binding fragment of claim 10, wherein the first Fc domain comprises SEQ ID NO:89, and wherein the second Fc domain comprises SEQ ID NO:90.

### Claim 12 (depends on 1)

The bispecific antibody or bispecific binding fragment of claim 1, comprising SEQ ID NO:79 as the amino acid sequence comprising (i) a scFv that binds CD79B and (ii) a first Fc domain, SEQ ID NO: 83 as the amino acid sequence comprising (i) the VH of a Fab that binds CD22 and (ii) a second Fc domain, and SEQ ID NO: 84 as the amino acid sequence comprising the VL of a Fab that binds CD22.

### Claim 13 (depends on 1)

An immunoconjugate comprising the bispecific antibody or bispecific binding fragment of claim 1 conjugated to a therapeutic agent or an imaging agent.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising the bispecific antibody or bispecific binding fragment of claim 1 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 1)

A polynucleotide encoding the bispecific antibody or bispecific binding fragment of claim 1.

### Claim 16

A method of modulating B cell activation, inhibiting aberrant B cell activation, decreasing B cell proliferation, decreasing cytokine production or reducing B cell activation in a subject, comprising administering an effective amount of a bispecific antibody or bispecific binding fragment to the subject for a time sufficient to modulate B cell activation, inhibit aberrant B cell activation, decrease B cell proliferation, decrease cytokine production or reduce B cell activation, wherein the bispecific antibody or bispecific binding fragment comprises a) a first antigen-binding arm that binds cluster of differentiation 79B protein (CD79B), comprising a first variable heavy domain (VH1) and further comprising a first variable light domain (VL1); and b) a second antigen-binding arm that binds cluster of differentiation 22 (CD22), comprising a second variable heavy domain (VH2) and further comprising a second variable light domain (VL2), wherein:
the VH1 comprises the HCDR1 of SEQ ID NO:9, the HCDR2 of SEQ ID NO: 10, and the HCDR3 of SEQ ID NO: 11, and the VL1 comprises the LCDR1 of SEQ ID NO:12, the LCDR2 of SEQ ID NO: 13, and the LCDR3 of SEQ ID NO: 14; and wherein
the VH2 comprises the HCDR1 of SEQ ID NO: 1, the HCDR2 of SEQ ID NO:2, and the HCDR3 of SEQ ID NO:3, and the VL2 comprising the LCDR1 of SEQ ID NO:4, the LCDR2 of SEQ ID NO:5, and the LCDR3 of SEQ ID NO:6.

### Claim 17

A bispecific antibody or bispecific binding fragment comprising:
a) a first antigen-binding arm that binds cluster of differentiation 79B protein (CD79B), comprising a first variable heavy domain (VH1) and further comprising a first variable light domain (VL1), wherein the first antigen-arm that binds CD79B comprises at least one selected from the group consisting of:
(i) the VH1 comprises the HCDR1 of SEQ ID NO:9, the HCDR2 of SEQ ID NO: 10, and the HCDR3 of SEQ ID NO:11; and the VL1 comprises the LCDR1 of SEQ ID NO: 12, the LCDR2 of SEQ ID NO: 13, and the LCDR3 of SEQ ID NO: 14;
(ii) the VH1 comprises the HCDR1 of SEQ ID NO:17, the HCDR2 of SEQ ID NO: 18, and the HCDR3 of SEQ ID NO: 19; and the VL1 comprises the LCDR1 of SEQ ID NO:20, the LCDR2 of SEQ ID NO:21, and the LCDR3 of SEQ ID NO:22;
(iii) the VH1 comprises the HCDR1 of SEQ ID NO:25, the HCDR2 of SEQ ID NO:26, and the HCDR3 of SEQ ID NO:27; and the VL1 comprises the LCDR1 of SEQ ID NO:28, the LCDR2 of SEQ ID NO:29, and the LCDR3 of SEQ ID NO:30;
(iv) the VH1 comprises the HCDR1 of SEQ ID NO:33, the HCDR2 of SEQ ID NO:34, and the HCDR3 of SEQ ID NO:35; and the VL1 comprises the LCDR1 of SEQ ID NO:36, the LCDR2 of SEQ ID NO:37, and the LCDR3 of SEQ ID NO:38;
(v) the VH1 comprises the HCDR1 of SEQ ID NO:41, the HCDR2 of SEQ ID NO:42, and the HCDR3 of SEQ ID NO:43; and the VL1 comprises the LCDR1 of SEQ ID NO:44, the LCDR2 of SEQ ID NO:45, and the LCDR3 of SEQ ID NO:46;
(vi) the VH1 comprises the HCDR1 of SEQ ID NO:49, the HCDR2 of SEQ ID NO:50, and the HCDR3 of SEQ ID NO:51; and the VL1 comprises the LCDR1 of SEQ ID NO:52, the LCDR2 of SEQ ID NO:53, and the LCDR3 of SEQ ID NO:54; and
(vii) the VH1 comprises the HCDR1 of SEQ ID NO:57, the HCDR2 of SEQ ID NO:58, and the HCDR3 of SEQ ID NO:59; and the VL1 comprises the LCDR1 of SEQ ID NO:60, the LCDR2 of SEQ ID NO:61, and the LCDR3 of SEQ ID NO:62; and
b) a second antigen-binding arm that binds cluster of differentiation 22 (CD22), comprising a second variable heavy domain (VH2) and further comprising a second variable light domain (VL2).

### Claim 18 (depends on 17)

The bispecific antibody or bispecific binding fragment of claim 17, wherein the first antigen-binding arm that binds CD79b comprises a VH and VL selected from the group consisting of:
a) the VH of SEQ ID NO: 15 and the VL of SEQ ID NO: 16;
b) the VH of SEQ ID NO: 23 and the VL of SEQ ID NO: 24;
c) the VH of SEQ ID NO: 31 and the VL of SEQ ID NO: 32;
d) the VH of SEQ ID NO: 39 and the VL of SEQ ID NO: 40;
e) the VH of SEQ ID NO: 47 and the VL of SEQ ID NO: 48;
f) the VH of SEQ ID NO: 55 and the VL of SEQ ID NO: 56;
g) the VH of SEQ ID NO: 63 and the VL of SEQ ID NO: 64; and
h) the VH of SEQ ID NO: 80 and the VL of SEQ ID NO: 81.

### Claim 19 (depends on 17)

The bispecific antibody or bispecific binding fragment of claim 17, wherein the first antigen-binding arm that binds CD79b comprises at least one selected from the group consisting of:
a) a VH1 comprising the HCDR1 of SEQ ID NO:9, the HCDR2 of SEQ ID NO: 10, and the HCDR3 of SEQ ID NO:11; and a VL1 comprising the LCDR1 of SEQ ID NO: 12, the LCDR2 of SEQ ID NO: 13, and the LCDR3 of SEQ ID NO: 14; and
b) the VH1 comprises SEQ ID NO: 80 and the VL1 comprises SEQ ID NO: 81.

### Claim 20 (depends on 17)

The bispecific antibody or bispecific binding fragment of claim 17, wherein each of the first antigen-binding arm and the second binding arm comprises at least one selected from the group consisting of a single-chain variable fragment (scFv), an (scFv) 2, an antigen-binding fragment (Fab), a F (ab′) 2, a Fd, a Fv, a VHH, and a dAB.

### Claim 21 (depends on 20)

The bispecific antibody or bispecific binding fragment of claim 20, wherein the first antigen-binding arm comprises an scFv, and the second antigen-binding arm comprises a Fab.

### Claim 22 (depends on 21)

The bispecific antibody or bispecific binding fragment of claim 21, wherein the first antigen-binding arm comprises an scFv having the amino acid sequence of SEQ ID NO:82.

### Claim 23 (depends on 17)

The bispecific antibody or bispecific binding fragment of claim 17, wherein the first antigen-binding arm that binds CD79b comprises a first Fragment crystallizable (Fc) domain, and wherein the second antigen-binding arm that binds CD22 comprises a second Fc domain, wherein at least one of the first and second Fc domain comprises one or more mutations that promote heterodimerization of the Fc domains, reduce Fc binding to a Fcγ receptor, reduce Fc binding to protein A, extend the half-life of the multispecific antibody or multispecific binding fragment, or any combination thereof.

### Claim 24 (depends on 23)

The bispecific antibody or bispecific binding fragment of claim 23, wherein at least one of the first and second Fc domain comprises one or more mutations selected from the group consisting of:
a) one or more mutations that promote heterodimerization of the Fc domains selected from the group consisting of T366S, L368A, T366W, and Y407V according to EU numbering;
b) one or more mutations that reduce Fc binding to a Fcγ receptor selected from the group consisting of L234A, L235A, and D265S according to EU numbering;
c) one or more mutations that reduce Fc binding to protein A selected from the group consisting of H435R and Y436F (EU numbering);
d) one or more mutations that extend the half-life of the bispecific antibody or bispecific binding fragment selected from the group consisting of M252Y, S254T, and T256E according to EU numbering.

### Claim 25 (depends on 24)

The bispecific antibody or bispecific binding fragment of claim 24, wherein at least one of the first and second Fc domain comprises one or more mutations selected from the group consisting of:
a) one or more mutations that promote heterodimerization of the Fc domains wherein the first Fc domain comprise mutation T366W, and wherein the second Fc domain comprises mutations T366S, L368A, and Y407V;
b) one or more mutations that reduce Fc binding to a Fcγ receptor, wherein both the first Fc domain and the second Fc domain comprise mutations L234A, L235A, and D265S;
c) one or more mutations that reduce Fc binding to protein A, wherein the second Fc domain comprises mutations H435R and Y436F;
d) one or more mutations that extend the half-life of the bispecific antibody or bispecific binding fragment wherein both the first Fc domain and the second Fc domain comprise mutations M252Y, S254T, and T256E.

### Claim 26 (depends on 25)

The bispecific antibody or bispecific binding fragment of claim 25, wherein the first Fc domain comprises SEQ ID NO:89, and wherein the second Fc domain comprises SEQ ID NO:90.

### Claim 27 (depends on 17)

An immunoconjugate comprising the bispecific antibody or bispecific binding fragment of claim 17 conjugated to a therapeutic agent or an imaging agent.

### Claim 28 (depends on 17)

A pharmaceutical composition comprising the bispecific antibody or bispecific binding fragment of claim 17 and a pharmaceutically acceptable carrier.

### Claim 29 (depends on 17)

A polynucleotide encoding the bispecific antibody or bispecific binding fragment of claim 17.