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Ptprs and proteoglycans in rheumatoid arthritis

A technology of immunoglobulins and analogs, applied in the direction of anti-animal/human immunoglobulins, immunoglobulins, peptides/protein components, etc.

Pending Publication Date: 2021-06-22
LA JOLLA INST FOR IMMUNOLOGY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, such therapies include significant side effects and can improve efficacy

Method used

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  • Ptprs and proteoglycans in rheumatoid arthritis
  • Ptprs and proteoglycans in rheumatoid arthritis
  • Ptprs and proteoglycans in rheumatoid arthritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0187] Example 1. Materials and methods

[0188] polypeptide

[0189] The following peptides were used in the experiments:

[0190] "In use" (SEQ ID NO: 16):

[0191] EEPPRFIREPKDQIGVSGGVASFVCQATGDPKPRVTWNKKGKKVNSQRFETIDFDESSGAVLRIQPLRTPRDENVYECVAQNSVGEITIHAKLTVLREDQLPPGFPNIDMGPQLKVVERTRTATMLCAASGNPDPEITWFKDFLPVDPSASNGRIKQLRSGALQIESSEETDQGKYECVATNSAGVRYSSPANLYVRTSGGGSLVPRGSEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0192] "Construct 1" (SEQ ID NO: 17):

[0193]ETGEEPPRFIREPKDQIGVSGGVASFVCQATGDPKPRVTWNKKGKKVNSQRFETIDFDESSGAVLRIQPLRTPRDENVYECVAQNSVGEITIHAKLTVLREDQLPPGFPNIDMGPQLKVVERTRTATMLCAASGNPDPEITWFKDFLPVDPSASNGRIKQLRSGALQIESSEETDQGKYECVATNSAGVRYSSPANLYVRTSGGGGSGGGGSEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT...

Embodiment 2

[0257] Combination therapy targeting synoviocytes for rheumatoid arthritis

[0258] The effect of TNF on the expression of PTPRS (encoding RPTPσ) was investigated in rheumatoid arthritis (RA) and osteoarthritis (OA) fibroblast-like synoviocytes (FLS). FLS was used between passage 4 and 10, and cells were synchronized in 0.1% FBS (serum-starved medium) for 24-48h, then stimulated with 50ng / ml TNF for 24h. RNA was extracted using RNeasy kit (Qiagen). Use for qRT-PCR cDNA was synthesized by III First-Strand Synthesis SuperMix (Life Technologies). With primer assay and from SABiosciences / Qiagen Green qPCR Mastermix, qPCR was performed on the Bio-Rad CFX384 Real-Time PCR Detection System. The manufacturer guarantees that the primer assay efficiency is greater than 90%. Each reaction was measured in triplicate using the technique and the data were normalized to the expression level of the housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Results are present...

Embodiment 3

[0275] Example 3. Synergistic reversal of arthritis by synoviocyte-targeted therapy and TNF immunomodulation

[0276] By treating mice with severe arthritis (clinical score of at least 8) with doses of Ig1&2 (0.1 mg) and murine etanercept (2 mg / kg) that were not effective in reversing severe arthritis as monotherapy, suboptimal Therapeutic synergy of therapeutic doses of Fc-Ig1&2 and murine etanercept in CIA. CIA was induced and scored as described above. Fc-Ig1 & 2 and murine etanercept were obtained and injected as described above. For histological scoring of mouse arthritic joints, whole hind paws were fixed in 10% formalin, decalcified, trimmed and embedded. Sections were prepared from tissue blocks and stained with hematoxylin and eosin, safranin-O or toluidine blue (HistoTox). Histopathological scoring was performed as described. Briefly, inflammation in the joints of arthritic mice was scored 0-4 based on hematoxylin-eosin staining according to the following criteri...

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PUM

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Abstract

Provided herein, inter alia, are pharmaceutical compositions methods thereof that include a first amount of a PTPRS de-clustering agent and a second amount of a TNF inhibitor or an IL-6 inhibitor in synergistic amounts. The synergistic combinations provide (a) amelioration of disease or one or more symptoms of disease or (b) delay of onset of disease or one or more symptoms of disease.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application No. 62 / 733,545, filed September 19, 2018, which is hereby incorporated by reference in its entirety. [0003] Statement Concerning Rights to Inventions Made Under Federally Sponsored Research and Development [0004] This invention was made with Government support under Grant No. R01 AR066053 issued by the National Institutes of Health. The US Government has certain rights in this invention. [0005] References to attachments to sequence listings, tables, or computer program listings submitted as ASCII text files [0006] The sequence listing written in file 048513-510001WO_SEQUENCE_LISTING_ST25.txt (created September 19, 2019, 76,475 bytes, machine format IBM-PC, MS Windows operating system) is hereby incorporated by reference. [0007] Background of the invention [0008] In the United States, about 5-8% of people suffer from autoimmune diseases. Researc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/24A61K38/17A61K45/06A61P1/00A61P19/02A61P29/00A61K39/00
CPCA61K45/06A61P1/00A61P19/02A61P29/00C07K2319/30C07K16/00A61K39/395A61K38/1793A61K38/465C12Y301/03048A61K2300/00A61P37/06A61K39/3955
Inventor N·博蒂尼
Owner LA JOLLA INST FOR IMMUNOLOGY
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