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

Stability-modulating linkers for use with antibody drug conjugates

A technology of stability, compounds, applied in drug combination, antibody, anti-animal/human immunoglobulin, etc.

Active Publication Date: 2017-05-31
PFIZER INC +1
View PDF14 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In other cases, the use of overly stable ADCs resulted in less than optimal payload release activity in targeted tumor 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
  • Stability-modulating linkers for use with antibody drug conjugates
  • Stability-modulating linkers for use with antibody drug conjugates
  • Stability-modulating linkers for use with antibody drug conjugates

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0278] The pharmaceutical compositions of the present invention and methods for their preparation will be readily apparent to those skilled in the art. Such compositions and methods for their preparation can be found, for example, in Remington's Pharmaceutical Sciences, 22nd Edition (Mack Publishing Company, 2012). The pharmaceutical compositions are preferably prepared under GMP conditions.

[0279] The pharmaceutical compositions of the invention may be prepared, packaged or sold in bulk, as a single unit dose or as a plurality of single unit doses. A "unit dose" as used herein is a discrete quantity of pharmaceutical composition containing a predetermined quantity of active ingredient. The amount of active ingredient is usually equal to the dose of active ingredient to be administered to the individual, or a convenient fraction of such a dose, for example, 1 / 2 or 1 / 3 of such a dose. Any art-accepted method for administering a peptide, protein or antibody may be suitably e...

Embodiment 1

[0325] Example 1: N~2~-benzoyl-L-lysyl-L-valyl-N-{4-[(8S,11S,12R)-11-[(2S)-butan-2- Base]-12-(2-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl -1-(1,3-Thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-2-oxoethyl)-5,5,10-trimethyl-3, 6,9-trioxo-8-(propan-2-yl)-2,13-dioxa-4,7,10-triazatetradec-1-yl]phenyl}-N~5 Preparation of ~-carbamoyl-L-ornithine (6)

[0326]

[0327] Step 1: N~2~-benzoyl-N~6~-(tert-butoxycarbonyl)-L-lysyl-L-valyl-N~5~-carbamoyl-N-[4- Synthesis of (Hydroxymethyl)phenyl]-L-ornithine (2). To N~2~-benzoyl-N~6~-(tert-butoxycarbonyl)-L-lysine (100mg, 0.285mmol) and L-valyl-N~5~-carbamoyl-N -[4-(Hydroxymethyl)phenyl]-L-ornithine (1,108 mg, 0.285 mmol) in 1 mL of N,N-dimethylformamide was added O-(7-azabenzo Triazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 111mg, 0.285mmol), followed by N,N-diisopropylethylamine (201ul , 149mg, 1.14mmol). The mixture was monitored by LC-MS and stirred at room temperature for 16 hours. The r...

Embodiment 2

[0331]Example 2: N~2~-(2,2-dimethylpropionyl)-L-lysyl-L-valyl-N-{4-[(8S,11S,12R)-11-[ (2S)-But-2-yl]-12-(2-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[ (1S)-2-Phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-2-oxoethyl)-5,5, 10-Trimethyl-3,6,9-trioxo-8-(propan-2-yl)-2,13-dioxa-4,7,10-triazatetradec-1-yl Preparation of ]phenyl}-N~5~-carbamoyl-L-ornithine (12)

[0332]

[0333] Step 1: N-(tert-Butoxycarbonyl)-L-valyl-N-{4-[(8S,11S,12R)-11-[(2S)-Butan-2-yl]-12-(2 -{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3 -thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-2-oxoethyl)-5,5,10-trimethyl-3,6,9-trioxo -8-(Propan-2-yl)-2,13-Dioxa-4,7,10-Triazatetradec-1-yl]phenyl}-N~5~-carbamoyl-L - Synthesis of ornithine (8). To 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2- Methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}- 5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (4,80 mg, 0.11 mmo...

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 invention provides stability-modulated antibody-drug conjugates, stability-modulating linker components used to make these stability-modulated antibody-drug conjugates, therapeutic methods using stability-modulated antibody-drug conjugates, and methods of making stability modulating linkers and stability-modulated antibody-drug conjugates.

Description

technical field [0001] The present invention relates to linkers for use in association with antibody-drug conjugates (ADCs) capable of up-regulating and down-regulating the extracellular and / or intracellular stability of the antibody-drug conjugates. The invention also relates to therapeutic uses and treatment regimens employing such clinically advantageous stability-modulated antibody-drug conjugates. Finally, the invention relates to methods of preparing stability-modulating linkers and stability-modulated antibody-drug conjugates. [0002] References to Sequence Listings [0003] This application is filed electronically via EFS-Web and includes the electronically filed Sequence Listing in .txt format. The .txt file contains a sequence listing titled "PC72108A_SEQ_LISTING_ST25.txt" created on August 14, 2015 and having a size of 10 KB. The sequence listing contained in this .txt file is an integral part of the specification and is incorporated herein by reference in its e...

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): C07K7/02A61K47/64A61K47/65A61K47/68A61P35/00
CPCA61K47/65A61K47/64A61P35/00A61P37/06A61K47/68031A61K47/6889A61K47/6851C07K16/30A61K2039/505C07K2317/94C07K2319/01C07K2319/35
Inventor R·G·杜申P·施特罗普M·G·多里沃尔斯科L·穆瓦纳
Owner PFIZER INC
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com