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

Methods for allogeneic hematopoietic stem cell transplantation

A hematopoietic stem cell, allogeneic technology, applied in blood/immune system cells, animal cells, extracellular fluid diseases, etc., can solve problems such as reducing the efficacy of transferred cells and restricting the use of allogeneic cells

Pending Publication Date: 2021-08-24
美真达治疗公司
View PDF158 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

HvG can significantly reduce the efficacy of transferred cells and generate adverse events in recipients, limiting the use of allogeneic cells

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
  • Methods for allogeneic hematopoietic stem cell transplantation
  • Methods for allogeneic hematopoietic stem cell transplantation
  • Methods for allogeneic hematopoietic stem cell transplantation

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0755] Preparation of antibody-drug conjugates

[0756] In the ADC of Formula I as disclosed herein, an anti-HC antibody (such as an anti-CD117 antibody or an anti-CD45 antibody) or an antigen-binding fragment thereof is linked to one or more cytotoxic drug moieties (D ) conjugated, for example, from about 1 to about 20 drug moieties per antibody. The ADCs of the present disclosure can be prepared in a variety of ways, using organic chemical reactions, conditions and reagents known to those skilled in the art, including: (1) Reactive substituents of antibodies or antigen-binding fragments thereof react with divalent linking reagents to form Ab-Z-L as described above, subsequently reacted with the drug moiety D; or (2) the reactive substituent of the drug moiety is reacted with a divalent linking reagent to form D-L-Z', subsequently reacted with the antibody or its antigen as described above The reactive substituents of the bound fragment react to form an ADC of formula D-L-...

Embodiment 1

[0766] Example 1: Anti-CD45 and anti-CD117 antibody drug conjugates realize allogeneic hematopoietic stem cell transplantation

[0767] Antibody drug conjugates (ADCs) targeting mouse CD45 or mouse CD117 were recently shown to effectively opsonize immunocompetent mice for whole bone marrow transplantation (Palchaudhuri et al. Nature Biotech 2016 34:738–745; and Czechowicz et al. al. Blood 2016 128:493). This innovative targeting approach utilizing ADCs for conditioning has the potential to be a therapeutic breakthrough if successfully applied to humans. Previously used anti-CD45 or anti-CD117 antibodies were conjugated to saporin, a ribosomal inhibitory protein, which, once internalized, causes cytotoxicity in a cell cycle-independent manner. Both anti-CD45-saporin (CD45-SAP) and anti-CD 117-saporin (CD117-SAP) ADCs have been shown to effectively deplete bone marrow hematopoietic stem cells (HSCs) as single-entity agents, thereby creating a gap that achieves effective autolo...

Embodiment 2

[0772] Example 2: CD45-Targeting Antibody Drug Conjugate Plus Post-Transplant Cyclophosphamide Sufficient to Achieve Allogeneic Bone Marrow Transplantation in a Minor Mismatch Mouse Model

[0773] Bone marrow transplantation (BMT) is a potentially curative treatment for malignant and non-malignant blood disorders. Current patient preparation or conditioning protocols prior to BMT limit the use of this curative procedure due to protocol-related mortality and morbidity, including organ toxicity, infertility / infertility, and risk of secondary malignancies. It was previously shown that targeted preparation using an antibody-drug conjugate (ADC) against mouse CD45 is sufficient to achieve bone marrow transplantation (BMT) in immunocompetent syngeneic mice (Palchaudhuri et al. Nature Biotech 2016 34:738– 745), and this preparation, if successfully applied to patients, has the potential to expand the utility of BMT. To further investigate the utility of anti-CD45 ADC (anti-CD45 anti...

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

Described herein are compositions and methods useful for the depletion of CD117+ or CD45+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. The compositions and methods described herein can be used to treat a disorder, for instance, by depleting a population of CD117+ or CD45+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for allogeneic hematopoietic stem cell transplant therapy and to improve the engraftment of allogeneic hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.

Description

[0001] related application [0002] This application claims U.S. Provisional Application No. 62 / 752,828, filed October 30, 2018; U.S. Provisional Application No. 62 / 773,873, filed November 30, 2018; and U.S. Provisional Application No. 62 / 882,362 priority. The entire content of each of the foregoing priority applications is incorporated herein by reference. technical field [0003] The present disclosure relates to the treatment of patients suffering from various pathologies, such as blood disorders, metabolic disorders, cancer, and autoimmune diseases, etc., by administering antibody drug conjugates capable of binding CD117 or CD45 expressed by hematopoietic cells, such as hematopoietic stem cells conduct. Background technique [0004] Allogeneic cell therapy involves the transplantation of cells into a patient, where the transplanted cells originate from a donor other than the patient. Common allogeneic donor types used for allogeneic cell therapy include HLA antigen-m...

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
IPC IPC(8): A61K47/68A61K45/06C07K16/28A61P37/06A61K35/28A61K39/395
CPCA61K35/28C07K16/2803A61K2039/545C07K16/289A61K47/6825A61K47/6849A61P37/06A61K45/06A61P7/00A61P3/00A61P35/00A61P37/00C12N5/0634A61K2300/00A61K2039/505C07K2317/565C07K2317/21C07K2317/92C07K2317/52A61K47/6817A61K31/675A61N5/10
Inventor R.帕尔乔杜里J.L.普罗克特G.O.吉拉德A.博伊塔诺S.海兹M.库克A.哈蒂根
Owner 美真达治疗公司
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