Meditopes and meditope-binding antibodies and uses thereof

• US 9,428,553 B2
• Filed: 02/11/2013
• Issued: 08/30/2016
• Est. Priority Date: 02/10/2012
• Status: Active Grant

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Williams, John C., Zer, Cindy, Bzymek, Krzysztof, Avery, Kendra Nicole
• Primary Examiner(s): LIEB, JEANETTE M
• Application Number:
  US13/764,762
• Publication Number:
  US 20140113348A1
• Time in Patent Office: 1,296 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 47/66 the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
• CPC Class Codes: A61K 47/6897 Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2299/00 Coordinates from 3D structures of peptides, e.g. proteins or enzymes
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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.

Claims

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-R³ (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

R³ 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.