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

B-cell reduction using cd37-specific and cd20-specific binding molecules

a b-cell and binding molecule technology, applied in the field of b-cell reduction, can solve the problems of insufficient b-cell activity, synergistic conjugations, inappropriate cell proliferation,

Inactive Publication Date: 2009-08-27
EMERGENT PRODUCTS DEVELOPMENT SEATTLE LLC
View PDF99 Cites 103 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The methods provide enhanced B-cell reduction and improved clinical responses compared to existing therapies, with reduced toxicity and increased penetration into lymphoid tissues, leading to better treatment outcomes for B-cell-related diseases and autoimmune disorders.

Problems solved by technology

In some of these methods, the combinations are synergistic.
For example, aberrant B-cell activity may include inappropriate proliferation of cells whose DNA or other cellular components have become damaged or defective.

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
  • B-cell reduction using cd37-specific and cd20-specific binding molecules
  • B-cell reduction using cd37-specific and cd20-specific binding molecules
  • B-cell reduction using cd37-specific and cd20-specific binding molecules

Examples

Experimental program
Comparison scheme
Effect test

example 1

Production of a CD37-Specific Binding Molecule

[0174]CD37-specific SMIPs are described in co-owned U.S. application Ser. No. 10 / 627,556 and U.S. Patent Publication Nos. 2003 / 133939, 2003 / 0118592 and 2005 / 0136049. An exemplary SMIP, TRU-016, is produced as described below.

[0175]TRU-016 [G28-1 scFv VH11S(SSC-P)H WCH2 WCH3] is a recombinant single chain protein that binds to the CD37 antigen. The binding domain was based on the G28-1 antibody sequence previously disclosed in the patent publications listed in the preceding paragraph, which disclosure is incorporated herein by reference. The binding domain is connected to the effector domain, the CH2 and CH3 domains of human IgG1, through a modified hinge region. TRU-016 exists as a dimer in solution and the dimer has a theoretical molecular weight of approximately 106,000 daltons.

[0176]Total RNA from the G28-1 hybridoma was isolated using Trizol RNA (Gibco) reagent according to the manufacturer's instructions. cDNA was prepared using 5 μ...

example 2

TRU-016 and Various CD37-Specific Antibodies Bind the Same or Overlapping Epitopes on CD37

[0186]Experiments were performed to identify the CD37 epitope bound by TRU-016 and other previously described CD37-specific antibodies.

[0187]Unconjugated MB371 (#555457) and FITC-conjugated MB371 (#555456) were obtained from BD Pharmingen (San Jose, Calif.), FITC-conjugated BL14 (#0457) from Immunotech / Beckman Coulter (Fullerton, Calif.), FITC-conjugated NMN46 (#RDI-CBL 136FT) and unconjugated NMN46 (#RDI-CBL 136) from RDI (Flanders, N.J.), FITC-conjugated IP024 (#186-040) and unconjugated IPO-24 (#186-020) from Ancell Corporation (Bayport, Minn.), FITC-conjugated HHI (#3081) and unconjugated HH1 (#3080) from DiaTec.Com (Oslo, Norway) and FITC-conjugated WR17 (YSRTMCA483F) and unconjugated WR17 (YSRTMCA483S) from Accurate Chemical & Scientific (Westbury, N.Y.). TRU-016 protein was produced as described in Example 1.

[0188]TRU-016 was conjugated to FITC at Trubion using a Molecular Probes Fluoror...

example 3

TRU-016 is Deficient in Binding C1q and Activating the Classical Complement Activation Pathway

[0198]Experiments were performed to explore why the TRU-016 dimer peak fails to mediate significant levels of complement dependent killing of B cell targets. One possibility was that TRU-016 dimer shows reduced binding to components of the complement cascade relative to normal human IgG1 antibody. Thus, experiments were performed to determine if TRU-016 activates the classical complement activation pathway by looking for TRU-016 binding to C1q. C1q, is a subunit of the C1 enzyme complex that activates the serum complement system, and is the recognition component of the classical complement activation pathway.

[0199]C1q binding studies were performed as previously described (Cragg et al., Blood 2004, 103:2738-2743). Briefly, Ramos B-cells in Iscoves media (#12440-053, Gibco / Invitrogen, Grand Island, N.Y.) with no serum were plated in 96-well V bottom plates at 5×105 / well in 100 μl. Cells were...

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

PropertyMeasurementUnit
half lifeaaaaaaaaaa
temperaturesaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

The present invention generally provides methods for B-cell reduction in an individual using CD37-specific binding molecules. In particular, the invention provides methods for B-cell reduction using CD37-specific binding molecules alone, or a combination of CD37-specific binding molecules and CD20-specific binding molecules, in some instances a synergistic combination. The invention further provides materials and methods for treatment of diseases involving aberrant B-cell activity. In addition, the invention provides humanized CD37-specific binding molecules.

Description

[0001]The present application is a continuation of U.S. patent application Ser. No. 11 / 493,132, filed Jul. 25, 2006, now pending, which claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 60 / 702,499, filed Jul. 25, 2005, and U.S. Provisional Application No. 60 / 800,595, filed May 16, 2006. All of the above-noted applications are incorporated herein by reference in their entireties.STATEMENT REGARDING SEQUENCE LISTING[0002]The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is 910180—404C1_SEQUENCE_LISTING.txt. The text file is 226 KB, was created on May 7, 2009, and is being submitted electronically via EFS-Web, concurrent with the filing of the specification.FIELD OF THE INVENTION[0003]The present invention generally provides methods for B-cell reduction in an individual using CD37-spec...

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(United States)
IPC IPC(8): A61K39/395C07K16/18
CPCA61K39/39558A61K39/3955A61K2039/505A61K2039/507A61K2039/545C07K16/2887C07K16/2896C07K2316/95C07K2317/24C07K2317/53C07K2317/56C07K2317/565C07K2317/567C07K2317/622C07K2317/72C07K2317/732C07K2317/734A61K45/06C07K2317/52C07K16/3061C07K16/30A61K2300/00C07K2317/73C07K2317/75C07K2317/76A61P1/04A61P17/00A61P17/06A61P19/02A61P21/00A61P21/04A61P25/00A61P27/02A61P29/00A61P35/00A61P35/02A61P37/00A61P37/02A61P37/06A61P43/00A61P3/10A61K39/395
Inventor GROSMAIRE, LAURA S.HAYDEN-LEDBETTER, MARTHA S.LEDBETTER, JEFFREY A.THOMPSON, PETER A.SIMON, SANDY A.BRADY, WILLIAM
Owner EMERGENT PRODUCTS DEVELOPMENT SEATTLE LLC
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