Humanized anti-trop-2 monoclonal antibodies and uses thereof
AssigneeAbruzzo Theranostic S.R.L.
InventorsEmanuela Guerra, Saverio Alberti
Life of this patent
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Abstract
The present invention refers to humanized anti-Trop-2 antibodies and their fragments, derivatives and conjugates that are able to recognise and bind with high affinity distinct regions of the Trop-2 molecule. The present invention also teaches the use of such antibodies and of pharmaceutical compositions thereof for diagnosis and therapy of human pathologies, in particular cancer.
Claims18
A humanized antibody, or fragments or conjugates thereof, which recognizes and binds the same epitope or epitopes as the antibody 2G10 produced by the hybridoma deposited in the Advanced Biotechnology Center (ABC) with the number PD 08020;
- (a) wherein the humanized antibody comprises (i) a variable domain framework region from a heavy chain of a human antibody or from a human consensus framework;
- and/or (ii) a variable domain framework region from a light chain of a human antibody or from a human consensus framework;
- and
- (b) wherein (i) at least one amino acid in the variable domain framework region from the heavy chain is substituted with a corresponding amino acid from a heavy chain of a mouse antibody or mouse consensus framework and/or (ii) at least one amino acid in the variable domain framework region from the light chain is substituted with a corresponding amino acid from a light chain of a mouse antibody or mouse consensus framework;
- and
- (c) wherein (i) the amino acid substitutions in the heavy chain are:
- F (murine) instead of Y (human) at position 27, and/or
- S (murine) instead of T (human) at position 30, and/or
- L (murine) instead of V (human) at position 37, and/or
- I (murine) instead of M (human) at position 48, and/or
- A (murine) instead of G (human) at position 49, and/or
- L (murine) instead of I (human) at position 70, and/or
- V (murine) instead of R (human) at position 72;
- and/or
- (ii) the amino acid substitution in the light chain is S (murine) instead of Y (human) at position 49;
- and
- (d) wherein the humanized antibody comprises (i) a heavy chain complementary determining region (CDRH3) amino acid sequence having the amino acid sequence of SEQ ID NO:9, and a heavy chain complementary determining region (CDRH2) amino acid sequence having the amino acid sequence of SEQ ID NO:8, and a heavy chain complementary determining region (CDRH1) amino acid sequence having the amino acid sequence of SEQ ID NO:7;
- and (ii) a light chain complementary determining region (CDRL3) amino acid sequence having the amino acid sequence of SEQ ID NO:
- 12, and a light chain complementary determining region (CDRL2) amino acid sequence having the amino acid sequence of SEQ ID NO:
- 11, and a light chain complementary determining region (CDRL1) amino acid sequence having the amino acid sequence of SEQ ID NO:
- 10.
Dependencies are inferred from the claim text.