# US 12,180,299 B2 · Multispecific antibody analogs comprising a common light chain, and methods of their preparation and use

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- Number: US 12,180,299 B2
- Document ID: US12180299B2
- Status: Granted
- Kind: B2
- Application number: 16/738,221
- Filed: 2020-01-09
- Published: 2020-07-16
- Granted: 2024-12-31
- Earliest claimed: 2014-04-01
- Assignees: Adimab, LLC
- Applicants: Adimab, LLC
- Inventors: Hemanta Baruah; Robert Mabry
- Web page: https://patentgrep.com/patent/US12180299B2

## CPC

- C07K 16/32: against translation products of oncogenes
- C07K 16/005: {constructed by phage libraries}
- C07K 16/065: {Purification, fragmentation}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/35: Valency
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/522: CH1 domain
- C07K 2317/524: CH2 domain
- C07K 2317/526: CH3 domain
- C07K 2317/53: Hinge
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/64: comprising a combination of variable region and constant region components
- 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)

## Abstract

Multispecific antibody analogs that co-engage at least two different antigens or epitopes, which may also be referred to as targets as used interchangeably throughout, said analogs comprising a common light chain, are provided, as well as methods for their production and use.

## Claims

### Claim 1

A method of identifying a common VL for use in the synthesis of a multispecific antibody, wherein:
(A) at least one first antigen binding region comprises a first VH and the common VL; and
(B) at least one second antigen binding region comprises a second VH and the common VL,
wherein:
(A) the first antigen binding region has specificity for a first antigen; and
(B) the second antigen binding region has specificity for a second antigen different from the first antigen,
and the method comprises the steps of:
(i) identifying one or more antigen binding regions having specificity for the first antigen, each of the antigen binding regions comprising: a first-antigen specific human VH; and a first-antigen specific human VL comprising a framework region of VK1-05, VK1-12, or VK3-11,
(ii) obtaining one or more of the first-antigen specific human VLs from (i),
(iii) identifying antigen binding regions having specificity for the second antigen, each of the antigen binding regions comprising a second-antigen specific human VH and a second-antigen specific human VL,
(iv) obtaining two or more of the second-antigen specific human VHs from (iii),
(v) preparing a restricted library comprising the two or more second-antigen specific human VHs obtained from (iv) and the one or more first-antigen specific human VLs obtained from (ii), wherein the restricted library does not comprise a first-antigen specific human VH from (i), and wherein the restricted library is a human IgG1 antibody library comprising at least 105 different human VHs and 1 to 2910 different human VLs,
(vi) performing a selection against the second antigen using the restricted library prepared in (v), and
(vii) identifying from the selection performed in (vi) at least one antigen binding region having specificity for the second antigen, the at least one antigen binding region comprising: a second-antigen specific human VH; and a human VL identical to a first-antigen specific human VL obtained in (ii), thereby identifying a common VL, wherein the common VL:
(a) has specificity for the first antigen when associated with at least one first-antigen specific human VH from (i), and
(b) has specificity for the second antigen when associated with at least one second-antigen specific human VH identified in (vii).

### Claim 2 (depends on 1)

The method of claim 1, wherein:
(a) the identifying in (i) is from a selection performed using a naïve library,
(b) the identifying in (iii) is from a selection performed using a naïve library, or
(c) the identifying in (i) is from a selection performed using a naïve library and the identifying in (iii) is from a selection performed using a naïve library.

### Claim 3

A method of identifying a common VL, wherein the common VL:
(a) has specificity for a first antigen, when associated with at least one VH, and
(b) has specificity for a second antigen, when associated with at least one VH different from the VH in (a),
and wherein the first antigen is different from the second antigen and the method comprises the steps of:
(i) obtaining one or more first-antigen specific human VLs from one or more antigen binding regions having specificity for the first antigen, each of the antigen binding regions comprising: a first-antigen specific human VH; and a first-antigen specific human VL comprising a framework region of VK1-05, VK1-12, or VK3-11,
(ii) identifying antigen binding regions having specificity for the second antigen, each of the antigen binding regions comprising a second-antigen specific human VH and a second-antigen specific human VL,
(iii) obtaining two or more of the second-antigen specific human VHs from (ii),
(iv) preparing a restricted library comprising the two or more second-antigen specific human VHs obtained from (iii) and the one or more first-antigen specific human VLs obtained from (i), wherein the restricted library does not comprise a first-antigen specific human VH according to (i), and wherein the restricted library is a human IgG1 library comprising at least 105 different human VHs and 1 to 10 different human VLs,
(v) performing a selection against the second antigen using the restricted library prepared in (iv), and
(vi) identifying from the selection performed in (v) at least one antigen binding region having specificity for the second antigen, the at least one antigen binding region comprising: a second-antigen specific human VH; and a human VL identical to a first-antigen specific human VL obtained in (i), thereby identifying a common VL from the selection performed in (v), wherein the common VL:
(a) has specificity for the first antigen when associated with at least one first-antigen specific human VH according to (i), and
(b) has specificity for the second antigen when associated with at least one second-antigen specific human VH identified in (vi).

### Claim 4 (depends on 3)

The method of claim 3, wherein the identifying in (ii) is from a selection performed using a naïve library.

### Claim 5 (depends on 1)

The method of claim 1, wherein, in (ii), at least one of the one or more first-antigen specific human VLs comprises a framework region of VK1-05.

### Claim 6 (depends on 1)

The method of claim 1, wherein, in (ii), at least one of the one or more first-antigen specific human VLs comprises a framework region of VK1-12.

### Claim 7 (depends on 1)

The method of claim 1, wherein, in (ii), at least one of the one or more first-antigen specific human VLs comprises a framework region of VK3-11.

### Claim 8 (depends on 3)

The method of claim 3, wherein, in (i), at least one of the one or more first-antigen specific human VLs comprises a framework region of VK1-05.

### Claim 9 (depends on 3)

The method of claim 3, wherein, in (i), at least one of the one or more first-antigen specific human VLs comprises a framework region of VK1-12.

### Claim 10 (depends on 3)

The method of claim 3, wherein, in (i), at least one of the one or more first-antigen specific human VLs comprises a framework region of VK3-11.