US 12,371,475 B2Granted

Nucleic acids encoding anchor modified antibodies and uses thereof

AssigneeRegeneron Pharmaceuticals, Inc.

InventorsJason Mastaitis, Andrew J. Murphy, John McWhirter, Vera Voronina, Jesper Gromada

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Abstract

Described herein are anchor-modified immunoglobulin polypeptides, wherein the anchor moors the immunoglobulin polypeptide to a receptor of interest. The anchor-modified immunoglobulin polypeptides are generally characterized at the N-terminus with an anchor, e.g., the receptor binding portion of a ligand that binds a receptor. Non-human animals genetically modified with recombinant immunoglobulin segments that encode the anchor-modified immunoglobulin polypeptides are capable of making the anchor-modified immunoglobulin polypeptides. Such non-human animals also provided, along with methods and compositions for making and using the non-human animals. Methods for producing anchor-modified immunoglobulins from non-human animals are also provided, as well as anchor-modified immunoglobulins generated therefrom.

Claims27

Dependent claims

A recombinant nucleic acid molecule comprising a modified immunoglobulin (Ig) variable (V) gene segment that encodes an anchor-modified Ig polypeptide,

wherein the modified Ig V gene segment comprises a nucleic acid sequence encoding the anchor between a nucleic acid sequence encoding an Ig signal peptide and a nucleic acid sequence encoding the framework region (FR) 1, complementarity determining region (CDR) 1, FR2, CDR2, FR3, and CDR3 of a germline Ig V gene segment, or a variant thereof,
wherein the anchor-modified Ig polypeptide comprises, in operable linkage:
(i) the Ig signal peptide,
(ii) the anchor, and
(iii) the FR1, CDR1, FR2, CDR2, FR3, and CDR3 of the germline Ig V gene segment, or a variant thereof,
wherein the anchor comprises a receptor binding portion of a non-immunoglobulin polypeptide of interest that binds a cognate receptor, and
optionally wherein the nucleic acid molecule lacks any other Ig V gene segments.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/555,616Filed 20 Dec 2021 · us provisional application
Priority: 23 Dec 2020
Published: US 2022/0195014 A123 Jun 2022
Granted: 29 Jul 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07K 14/723
For hormones: g protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor
G01N 33/6851
Methods of protein analysis involving mass spectrometry: methods of protein analysis involving laser desorption ionisation mass spectrometry
C07K 14/58
Hormones: atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Cardionatrin; Cardiodilatin
C07K 16/06
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: from serum