Human antibodies, pharmaceutical compositions and methods

A technology of antibodies and carbohydrates, applied in drug combinations, chemical instruments and methods, antibodies, etc., can solve problems such as limitations of applicability and binding characteristics

Active Publication Date: 2019-07-26
OBI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this technique yields many useful antibodies, its applicability is limited by differences in binding properties between antibodies expressed in bacteria and eukaryotic cells

Method used

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  • Human antibodies, pharmaceutical compositions and methods
  • Human antibodies, pharmaceutical compositions and methods
  • Human antibodies, pharmaceutical compositions and methods

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0284] Embodiment 1: clinical sample collection

[0285] To generate human monoclonal antibodies against Globo series antigens, B cells were isolated from the peripheral blood of vaccinated patients. After administration of Globo H-KLH vaccine (OBI-822 / OBI-821 ) in recurrent ovarian cancer patients, blood samples were collected for the following analytical procedures.

Embodiment 2

[0286] Example 2: Sorting and culturing of human single B cells

[0287] IgD freshly isolated from human peripheral blood - IgM - IgA - Memory B cells and dispensed into 384-well tissue culture plates at a density of 1 cell per well using a fluorescence-activated cell sorter. Sorted B cells were stimulated to secrete IgG and incubated for several days. After incubation, B cell lysates and culture supernatants were collected separately.

Embodiment 3

[0288] Example 3: Amplification of antibody genes

[0289] In obtaining Globo H, SSEA-3 or SSEA-4 binding clones, genes encoding Ig VH, IgVκ or IgVλ were recovered from B cell lysates using RT-PCR and cloned into IgG expression vectors. Recombinant antibodies are expressed by transfection of mammalian cells and used to confirm binding specificity or perform other functional assays.

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PUM

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Abstract

Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to Globo H, stage-specific embryonic antigen 3 (SSEA-3) and stage-specific embryonic antigen 4 (SSEA-4)are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cellsurfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as sarcoma, skin cancer, leukemia, lymphoma, brain cancer, glioblastoma, lung cancer, breast cancer, oral cancer, head-and-neck cancer, nasopharyngeal cancer, esophagus cancer, stomach cancer, liver cancer, bile duct cancer, gallbladder cancer, bladder cancer, pancreatic cancer, intestinal cancer, colorectal cancer, kidney cancer, cervix cancer, endometrial cancer, ovarian cancer, testical cancer, buccal cancer, oropharyngeal cancer, laryngeal cancer and prostate cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 368,407, filed July 29, 2016. The entire content of the above application is incorporated herein by reference. [0003] field of invention [0004] The present disclosure relates to human antibodies and binding fragments thereof that bind carbohydrate antigens, as well as nucleic acids encoding such antibodies, complementary nucleic acids, polypeptides, vectors, host cells, and methods of making and using them, including those comprising said antibodies and / or binding fragments pharmaceutical composition. Additionally, methods of administering an antibody to a subject in an amount effective to inhibit cancer cells are provided. Specifically, disclosed herein are antibodies that bind stage-specific embryonic antigen 3 (SSEA-3), stage-specific embryonic antigen 4 (SSEA-4), and GloboH, as well as related compositions and methods of use. Methods...

Claims

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Application Information

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IPC IPC(8): C07K16/44A61K49/16G01N33/574A61K39/00
CPCG01N33/574A61K49/0002G01N2400/02C07K16/18C07K16/30C07K2317/21C07K2317/92C07K16/44C07K2317/33A61P35/00A61P43/00A61K47/68A61K49/16A61K2039/505A61K47/6851A61K45/06C07K2317/54C07K2317/55C07K2317/565C07K2317/622C07K2317/73A61K39/39591A61K39/39583
Inventor C-D·T·游曾婉莹李书宇赖建勋陈怡如
Owner OBI PHARMA
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