Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Cd3/cd33 bispecific binding molecules

A bispecific, molecular-binding technology, applied to specific peptides, anti-receptors/cell surface antigens/cell surface determinant immunoglobulins, drug combinations, etc., can solve problems such as small binding affinity and long half-life

Inactive Publication Date: 2020-05-19
CILAG GMBH INT
View PDF9 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Therefore, there is a need for new engineered Fcγ sequences that have no or minimal binding affinity for FcγR and C1q, but retain a long half-life

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Cd3/cd33 bispecific binding molecules
  • Cd3/cd33 bispecific binding molecules
  • Cd3/cd33 bispecific binding molecules

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0193] 1. A bispecific binding molecule specifically binding to CD3 and CD33, said bispecific binding molecule comprising:

[0194] A CD33-binding polypeptide comprising SEQ ID NO:36 or SEQ ID NO:38 covalently coupled to the C-terminus of a light chain of an antibody that specifically binds CD3, said antibody comprising an IgG1 Fc region, said region comprising a CH2 domain in which the amino acid at position 265 is different from aspartic acid (D), the amino acid at position 297 is different from asparagine (N), and the amino acid at position 329 is different from proline Acid (P), where numbering is indicated by the EU index in Kabat.

[0195] 2. The bispecific binding molecule of embodiment 1, wherein

[0196] i. the amino acid at position 265 is alanine (A), asparagine (N) or glutamic acid (E),

[0197] ii. the amino acid at position 297 is alanine (A), aspartic acid (D) or glutamine (Q), and

[0198] iii. The amino acid at position 329 is alanine (A), glycine (G) or se...

example

[0233] The following examples are provided to supplement the existing disclosure and provide a better understanding of the subject matter described herein. These examples should not be viewed as limiting the described subject matter. It should be understood that the examples and embodiments described herein are for illustrative purposes only, and that various modifications or changes therefrom will be apparent to those skilled in the art and are to be included therein and can be made without departing from this document. made without the scope of the invention.

example 1

[0234] Example 1. Expression and purification of Fc mutated antibodies

[0235] Several antibodies with different mutations in the CH2 domain were produced based on mAb1 (mAb1 is a human IgG1 antibody specific for human CD3). The mutations are:

[0236] -i) N297A,

[0237] -ii) D265 plus P329A (DAPA),

[0238] -iii) D265 plus N297A plus P329A (DANAPA), and

[0239] -iv) L234A plus L235A (LALA)

[0240] (EU numbering according to Kabat (Kabat, E.A. (1991). Sequences of proteins of immunological interest [ Protein sequences of immunological significance ], Bethesda, MD: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, 1991).

[0241] For expression of antibodies, a leader sequence is usually present, which is excised and no longer present in the secreted product. An example of a leader sequence for expression in the examples described herein is provided in SEQ ID NO:42, and an example of a nucleotide sequence encoding the ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Advantageous bispecific binding molecules that comprise a CD3 binding and a CD33 binding part are provided. The CD3 binding part comprises an antibody that has variations in the Fc region with reducedbinding to C1q and Fc[gamma] receptors. The bispecific binding molecules can be used in the treatment of cancer.

Description

technical field [0001] 本文提供的公开内容涉及与CD3和CD33特异性结合的双特异性结合分子,其包含结合CD3的抗体部分,所述结合CD3的抗体部分包含突变的人抗体IgG1恒定区(Fc区),以保持FcRn结合,但基本失去了特异性结合Fcγ受体和C1q的能力。 Background technique [0002] 识别CD3和癌细胞表面抗原的双特异性结合分子是本领域已知的。它们典型地能够将任何种类的细胞毒性T细胞连接到癌细胞,而不依赖于T细胞受体特异性、共刺激或肽抗原呈递。已经描述了此类分子的几种形式,其中一种被称为BiTE(双特异性T细胞接合剂)的形式显示了迄今为止在临床上最大的成功。这种形式基于两个单链抗体通过肽接头共价连接,从而形成双特异性scFv抗体片段形式。WO 2014 / 170063将FynomAb形式描述为具有比此类BiTE形式具有优势。 [0003] CD33或Siglec-3是在骨髓系细胞上表达的跨膜受体。CD33可用作治疗急性髓性白血病的靶标。人CD33由NCBI参考序列:NP_001763.3)表示,并且已在本领域中进行了描述。 [0004] WO 2014 / 170063公开了具有与CD33结合的Fynomer部分和与CD3结合的抗体部分的FynomAb(例如,COVA467,是其中优选的CD3和CD33结合分子)。 [0005] COVA467中的CD3抗体部分包含在IgG1 Fc区中所谓的’LALA’突变(L234A和L235A,也称为“Ala-Ala”或“LALA”,其中编号是根据Kabat等人的Sequences of Proteins ofImmunological Interest[免疫学目的蛋白质序列],第5版.Public Health Service[公共卫生署],National Institutes of Health[国立卫生研究院],贝塞斯达,马里兰州(1991)中的EU索引进行的)。这些突变降低了C1q和FcγR结合,并且结果降低了效应子功能。 [0006] 然而,看起来具有所述LALA突变的IgG1仍具有残留的FcR结合活性和不完全沉默。因此,所述COVA467分子可能具有不希望的FcR依赖性T细胞活化的风险。 [0007] 在本领域中已经描述...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07K16/00C07K16/28C07K16/32A61P35/00A61K39/00
CPCA61K2039/507A61P35/00C07K16/00C07K16/2803C07K16/2809C07K16/2818C07K16/32C07K2317/24C07K2317/31C07K2317/33C07K2317/52C07K2317/524C07K2317/71C07K2317/92C07K2317/94A61K2039/505C07K16/468
Inventor S·S·布拉克K·克卢普施I·阿廷杰-托勒F·布勒A·祖姆斯特格J·贝尔采钦格D·格拉布洛夫斯基V·贝利斯维尔J·罗凯特R·肖尔茨R·桑迪玛利亚D·森E·凯奇C·阿尔巴尼
Owner CILAG GMBH INT
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com