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Anti-cd3 antibodies and uses thereof

An antibody and antigen technology, applied in the direction of antibodies, antibody medical components, anti-tumor drugs, etc., can solve problems such as unfavorable pharmacokinetics, immunogenicity and manufacturing

Pending Publication Date: 2021-06-04
JANSSEN BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the clinical utility of many T cell-recruiting bispecific antibodies is limited by challenges including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing issues

Method used

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  • Anti-cd3 antibodies and uses thereof
  • Anti-cd3 antibodies and uses thereof
  • Anti-cd3 antibodies and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0206] Preparation of immunogenic antigens and production of monoclonal antibodies can be performed by any suitable technique such as recombinant protein production. The immunogenic antigen can be administered to the animal as a purified protein or protein mixture (including whole cells or cell or tissue extracts), or the antigen can be formed de novo in the animal from nucleic acid encoding the antigen or a portion thereof.

[0207] Generation and use of bispecific and multispecific CD3 antibodies

[0208] The present invention provides bispecific and multispecific antibodies comprising a first domain that specifically binds CD3 and a second domain that specifically binds a second antigen. The second antigen can be a tumor associated antigen (TAA) or an antigen on a pathogenic cell.

[0209] Exemplary anti-CD3 antibodies that can be used to engineer bispecific and multispecific antibodies comprising a first domain that specifically binds CD3 and a second domain that specif...

Embodiment approach

[0565] The present invention provides the following non-limiting embodiments.

[0566] 1. An isolated recombinant anti-CD3 antibody or antigen-binding fragment thereof, comprising:

[0567] a) a heavy chain and a light chain comprising: a heavy chain complementarity determining region (HCDR) 1 comprising SEQ ID NO:662, a HCDR2 comprising SEQ ID NO:663 and a HCDR3 comprising SEQ ID NO:664, wherein The light chain comprises: a light chain complementarity determining region (LCDR) 1 comprising SEQ ID NO: 671, an LCDR2 comprising SEQ ID NO: 673 and an LCDR3 comprising SEQ ID NO: 690;

[0568] b) a heavy chain variable region comprising SEQ ID NO:652 and a light chain variable region comprising SEQ ID NO:661;

[0569] c) a heavy chain comprising SEQ ID NO:640 and a light chain comprising SEQ ID NO:676;

[0570] d) a heavy chain comprising: HCDR1 comprising SEQ ID NO:662, HCDR2 comprising SEQ ID NO:663 and HCDR3 comprising SEQ ID NO:664, and a light chain comprising: comprising SE...

Embodiment

[0652] 1 De novo production and functional characterization of anti-CD3 mAbs

[0653] 1-1 Immunization with CD3 antigen to generate CD3 monoclonal antibodies

[0654] Immunization with a proprietary vector (Aldevron, Fargo, North Dakota, USA) encoding Human CD3e and Human CD3d; Cynomolgus CD3e and Cynomolgus CD3d. Animals received alternating boosts of human and cynomolgus DNA. From the 6th administration, animals received the optimized vector with the same insert. Cells from lymph nodes were fused with the Ag8 myeloma cell line. After IgM depletion, 40 million cells from confluent BLWs were plated on three 96-well plates. In the absence of IgM depletion, 133 million cells from confluent BLX were plated on nine 96-well plates.

[0655] Analysis of fusion BLW (bead depletion of lymphocytes) and BLX (bead depletion of lymphocytes) by cell-based ELISA (CELISA) on cells transiently transfected with human and cynomolgus cDNA cloned into the selection vector depleted)...

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Abstract

The present invention relates to antibodies that specifically bind CD3. The present invention relates to antibodies that specifically bind PSMA. The present invention relates to antibodies that specifically bind CD3 and PSMA. The present invention relates to antibodies that specifically bind IL1RAP. The present invention relates to antibodies that specifically bind CD33. The present invention relates to antibodies that specifically bind CD3 and IL1RAP. The present invention relates to antibodies that specifically bind CD3 and CD33. The present invention relates to antibodies that specifically bind TMEFF2. The present invention relates to antibodies that specifically bind CD3 and TMEFF2. The present invention relates to fragments of the antibodies, polynucleotides encoding the antibodies or fragments thereof, and methods of making and using the same.

Description

[0001] sequence listing [0002] This application contains a Sequence Listing that has been electronically filed in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy created on May 3, 2019 is named JBI5135WOPCT1_Sequence_listing.txt and is 588KB in size. technical field [0003] The disclosure provided herein relates to anti-CD3 antibodies and antigen-binding fragments thereof capable of specifically binding to human and non-human non-human cluster of differentiation 3 (CD3), and in particular to cross-crossing with CD3 of non-human mammals (eg, cynomolgus monkeys) Reactive anti-CD3 antibodies and antigen-binding fragments; PSMA antibodies and antigen-binding fragments thereof that can specifically bind to human and non-human prostate-specific membrane antigen (PSMA); IL1RAP antibodies that can specifically bind to human and non-human IL1RAP and Antigen-binding fragments thereof; CD33 antibodies and antigen-binding fragments thereof capabl...

Claims

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Application Information

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IPC IPC(8): C07K16/28C07K14/47C07K16/30A61P35/00A61P35/02
CPCA61K2039/505C07K16/2809C07K2317/565C07K2317/515C07K2317/51C07K2317/75C07K2317/33C07K2317/92C07K2317/31C07K2317/94C07K16/3069C07K2317/55A61P35/00C07K2317/71C07K2317/24C07K16/2866C07K16/2803A61P35/02C07K16/28A61K39/39541C07K2317/21
Inventor F·高德特J·吉尔斯-科马尔B·海德里奇C·黄C·凯恩R·麦克达德J·内梅斯-西伊
Owner JANSSEN BIOTECH INC
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