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Immunoconjugates comprising mutant interleukin-2 and an anti-CD8 antibody

A technology of immunoconjugates and interleukins, applied in the field of immunoconjugates

Inactive Publication Date: 2022-02-15
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0014] However, tumors may be able to evade this targeting by shedding, mutating, or downregulating the antibody's target antigen

Method used

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  • Immunoconjugates comprising mutant interleukin-2 and an anti-CD8 antibody
  • Immunoconjugates comprising mutant interleukin-2 and an anti-CD8 antibody
  • Immunoconjugates comprising mutant interleukin-2 and an anti-CD8 antibody

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preparation example Construction

[0100] The term "pharmaceutical composition" refers to a preparation which is in a form which allows the biological activity of the active ingredients contained in the preparation to be effective and which does not contain a or additional components with unacceptable toxicity.

[0101] "Pharmaceutically acceptable carrier" refers to non-toxic components in a pharmaceutical composition other than the active component to the subject. Pharmaceutical carriers include, but are not limited to, buffers, excipients, stabilizers, or preservatives.

[0102] As used herein, "treatment" (and its grammatical variants, such as "treat" or "treating") refers to an attempt to alter the natural course of the disease in the individual being treated, and may be performed to treat Clinical interventions for prevention or performed during clinical pathology. Desired effects of treatment include, but are not limited to, prevention of occurrence or recurrence of disease, alleviation of symptoms, at...

example

[0294] The following are examples of methods and compositions of the invention. It is understood that various other embodiments may be practiced, given the general description provided above.

example 11

[0296] Example 1.1 Production of anti-CD8-IL2v TA conjugates and anti-CD8-IL2v OA conjugates targeting human CD8

[0297] The abbreviation "TA" means "double arm" herein. The abbreviation "OA" means "single arm" herein. The terms "anti-CD8-IL2vTA" and "CD8-IL2v TA" are used interchangeably herein. The terms "anti-CD8-IL2v OA" and "CD8-IL2v OA" are used interchangeably herein.

[0298] Expression of all genes is under the control of the human CMV promoter-intron A-5'UTR cassette. The BGH polyadenylation signal is located downstream of the gene. For use in HEK293 EBNA cells, the vector contains an oriP element for stable episomal maintenance of the plasmid.

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Abstract

The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to CD8. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

Description

technical field [0001] The present invention relates generally to immunoconjugates, and in particular to immunoconjugates comprising interleukin-2 polypeptide mutants and antibodies that bind to CD8, said immunoconjugates being only specific for CD8 + Cells have strong cis-targeting. Furthermore, the present invention relates to polynucleotide molecules encoding said immunoconjugates, as well as vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing said mutant immunoconjugates, pharmaceutical compositions comprising said mutant immunoconjugates, and uses thereof. Background technique [0002] Interleukin-2 (IL-2), also known as T cell growth factor (TCGF), is a 15.5 kDa globular sugar that plays a central role in lymphocyte production, survival, and homeostasis protein. It has a length of 133 amino acids and consists of four antiparallel amphipathic α-helices forming a quadruple structure essential for its ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N15/85C12N5/10A61K38/20A61K47/64A61P35/00
CPCC07K16/2815C07K14/55C12N15/85C12N5/0686A61K38/2013A61K47/6425A61P35/00C12N2800/107C12N2510/00C07K2319/30A61K2039/505C07K2319/00A61K38/00
Inventor A·弗里莫瑟-格伦德舍伯C·克雷恩P·尤马纳I·瓦尔德豪尔
Owner F HOFFMANN LA ROCHE & CO AG
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