Meditopes and meditope-binding antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-9428553-B2
Application number	US-201313764762-A
Country	US
Kind code	B2
Filing date	Feb 11, 2013
Priority date	Feb 10, 2012
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

Abstract

Antibodies and meditopes that bind to the antibodies are provided, as well as complexes, compositions and combinations containing the meditopes and antibodies, and methods of producing, using, testing, and screening the same, including therapeutic and diagnostic methods and uses.

First claim

What is claimed is:

1. A peptide having the formula:
R 1A —L 1A -R 2A

wherein:
R 1A is a meditope comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 16-18, 23, 29, 31, 32, 36, 39, 42, 43, 45, 46, 51, 52, 54, and 55;
L 1A is a linker of about 2 Å to about 100 Å in length; and
R 2A is a peptidyl kappa light chain binding moiety that binds to the peptidyl kappa light chain of the meditope-enabled antibody without decreasing antigen binding of the meditope-enabled antibody, wherein R 2A comprises the sequence:
X13-VTI-X14-VN-X15-IFADG-X16-IQTA-X17-F-X18-GTFEEATAEAYR-X19-AALLA-X20-VNGEYTADLEDGGNHMNI-X21-FAG-R 3 (IG) (SEQ ID NO: 184),

wherein:
X13 is Glu or null;
X14 is Arg, Lys, or a conjugated amino acid;
X15 is Lys, a conjugated amino acid, or Leu;
X16 is Lys or a conjugated amino acid;
X17 is Glu or Pro;
X18 is Pro, Arg, Lys, or a conjugated amino acid;
X19 is Tyr or Trp;
X20 is Arg, Lys, or conjugated amino acid;
X21 is Lys or a conjugated amino acid; and
R 3 is null or a conjugated peptidyl moiety.

2. The peptide of claim 1 , wherein L 1A is a peptidyl linker or a PEG linker.

3. The peptide of claim 1 , wherein L 1A is a peptidyl linker.

4. The peptide of claim 1 , wherein L 1A is a peptidyl linker consisting of five amino acids.

5. The peptide of claim 1 , wherein L 1A is about 5 Å to about 40 Å in length.

6. The peptide of claim 1 , wherein L 1A is about 10 Å to about 25 Å in length.

7. The peptide of claim 1 , wherein L 1A is about 18 Å in length.

8. The peptide of claim 4 , wherein said peptidyl linker consists of amino acids selected from the group consisting of alanine, glycine, serine, glutamic acid, glutamine, proline, arginine, lysine, threonine, and aspartic acid.

9. The peptide of claim 4 , wherein said peptidyl linker consists of amino acids selected from the group consisting of alanine, glycine, serine, glutamic acid, glutamine, threonine, and aspartic acid.

10. The peptide of claim 4 , wherein said peptidyl linker consists of amino acids selected from the group consisting of glycine, serine, and glutamic acid.

11. The peptide of claim 4 , wherein said peptidyl linker consists of amino acids selected from the group consisting of glycine and serine.

12. The peptide of claim 4 , wherein said peptidyl linker has the sequence -GGGGS- or -GGGGG-.

13. The peptide of claim 1 , wherein the linker comprises a proteolytic cleavage site that is an MMP cleavage site, an ADAM cleavage site, or a cathepsin cleavage site.

14. The peptide of claim 13 , wherein the proteolytic cleavage site is an MMP cleavage site.

15. The peptide of claim 1 , wherein said conjugated peptidyl moiety comprises a metal chelator bound to a metal ion, a small molecule, a chemotherapeutic agent, a therapeutic antibody or a functional fragment thereof, a toxin, a radioisotope, an enzyme, a nuclease, a hormone, an immunomodulator, an oligonucleotide, an organic or inorganic nanoparticle, an RNAi molecule, an siRNA, a boron compound, a photoactive agent, a dye, a fluorescent or luminescent substance, an enzyme, an enhancing agent, a radioactive substance, or a chelator.

Assignees

• Hope City

Inventors

• Williams John C
• Zer Cindy
• Bzymek Krzysztof
• Avery Kendra Nicole

Classifications

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title