Unlock instant, AI-driven research and patent intelligence for your innovation.

Anti-HIV vaccine antibodies with reduced multi-reactivity

A technology of antibodies and antigens, applied in the direction of antibodies, antiviral immunoglobulins, medical preparations containing active ingredients, etc., can solve problems such as difficulties in improvement

Pending Publication Date: 2022-06-17
CALIFORNIA INST OF TECH +1
View PDF176 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are various known ways to improve the biophysical properties of antibodies, improving these properties without sacrificing much of the antibody's neutralizing activity has been difficult

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
  • Anti-HIV vaccine antibodies with reduced multi-reactivity
  • Anti-HIV vaccine antibodies with reduced multi-reactivity
  • Anti-HIV vaccine antibodies with reduced multi-reactivity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0420] This example describes the materials and methods used in the subsequent examples below.

[0421] Polyreactivity assay: as described ( et al. 2012, mAbs, 4:6, 753-760), polyreactivity assay using ELISA to detect non-specific binding to baculovirus extract. Briefly, a solution of 1% baculovirus particles in 100 mM sodium bicarbonate buffer pH 9.6 was absorbed into the wells of a 384-well ELISA plate (Nunc Maxisorp) using a Tecan Freedom Evo liquid handling robot and the plate was incubated at 4°C. Incubate overnight. Plates were blocked with 0.5% BSA in PBS for 1 hour at room temperature. Purified IgG (diluted to 1 μg / mL in PBS with 0.5% BSA) was added to blocked assay plates and incubated for 3 hours at room temperature. Bound IgG was detected with a luminescent signal at 425 nm using HRP-conjugated anti-human IgG (H&L) secondary antibody (Genscript) and SuperSignal ELISA Femto Maximum Sensitivity Substrate (Thermo Fisher Scientific).

[0422] Neutralization assay: ...

Embodiment 2

[0426] The parental antibody NIH45-46 G54W consists of NIH45-46 HC paired with NIH45-46 LC with the G54W mutation. New antibody variants have mutations in one or both of the chains.

[0427] The single chain used to construct the new antibody variant is:

[0428] Chain name description (mutations listed using standard Kabat numbering)

[0429] HC1 HC NIH45-46 G54W HC with T68D SAP10 LC NIH45-46LC with Q27E, S28H and S30D SAP10T LC NIH45-46LC with Q27E, S28H, S30D and S74T SAP10T-LS LC NIH45-46LC with Q27E, S28H, S30D, S74T, M428L and N434S SAP3 LC NIH45-46LC with Q27E, S28Y and S30D SAP8 LC NIH45-46LC with Q27D, S28H m2 LC NIH45-46LC with S28Y

[0430] The new antibody reagent consists of the following HC / LC pairings (LS denotes a mutation in the Fc region previously described, eg M428L / N434S):

[0431] HC1 / SAP10

[0432] HC1 / SAP10-LS

[0433] HC1 / SAP10T

[0434] HC1 / SAP10T-LS

[0435] HC1 / SAP8

[0436] HC1 / SAP...

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

The present disclosure provides novel broadly neutralizing anti-HIV antibodies and antigen binding fragments thereof. The disclosed anti-HIV antibodies exhibit improved biophysical properties, such as reduced multi-reactivity, extended half-life, while maintaining broad and potent neutralizing activity. The disclosed anti-HIV bNAb variants constitute a new therapeutic strategy for the treatment and / or prevention of HIV infection.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority under 35 U.S.C. §119(e) to US Provisional Patent Application No. 62 / 871,393, filed July 8, 2019. The above application is incorporated herein by reference in its entirety. [0003] Statement Regarding Federally Funded Research [0004] This invention was made with government support under grants P01AI100148 and R01AI29784 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention. technical field [0005] The present invention relates to broad and potent antibodies against Human Immunodeficiency Virus ("HIV"). Background technique [0006] HIV causes Acquired Immune Deficiency Syndrome (AIDS), a human condition whose clinical features include wasting syndrome, central nervous system degeneration and severe immunosuppression leading to life-threatening opportunistic infections and malignant tumor. Since its discovery in 1981, HIV type 1 (HI...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/10A61P31/18
CPCA61P31/18C07K16/1063C07K2317/94C07K2317/76C07K2317/92C07K2317/21C07K2317/565C07K2317/567C07K2317/33C07K16/1045A61K2039/505A61K39/42A61K45/06C07K2317/31
Inventor S·A·西弗斯J·凯夫M·C·纽森茨威格P·J·比约克曼
Owner CALIFORNIA INST OF TECH