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US 12,180,299 B2Granted
Multispecific antibody analogs comprising a common light chain, and methods of their preparation and use
AssigneeAdimab, LLC
InventorsHemanta Baruah, Robert Mabry
Life of this patent
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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.
Claims10
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).
18 more elements
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).
12 more elements
Dependencies are inferred from the claim text.