Meditopes and related meditope-monoclonal antibody delivery systems, synthesis and therapeutic uses thereof

• US 8,658,774 B2
• Filed: 10/10/2011
• Issued: 02/25/2014
• Est. Priority Date: 10/08/2010
• Status: Active Grant

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Williams, John C., Horne, David A., Ma, Yuelong, Chang, Heng Wei
• Primary Examiner(s): Sang, Hong
• Application Number:
  US13/270,207
• Publication Number:
  US 20120177568A1
• Time in Patent Office: 869 Days
• Field of Search: None
• US Class Current: 530/413
• 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 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61K 47/6897 Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 39/04 Chelating agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• 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 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• 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 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 7/64 Cyclic peptides containing only normal peptide links
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Meditope variants and methods for their use are provided herein. A meditope variant as described herein comprises a peptide having a sequence CQFDLSTRRLKC (SEQ ID NO:1) or CQYNLSSRALKC (SEQ ID NO:2) that has one or more modifications at of least one amino acid residue of the sequence. Multivalent meditope variant tethering entities are also provided. Such entities may include two or more meditopes coupled via a long linker, multivalent scaffold, biotin-streptavidin, or IgG Fc domain. Further, methods of treating, imaging or diagnosing a disease or condition are provided. Such methods may include administering a therapeutically effective amount of a pharmaceutical composition to a subject, the pharmaceutical compound comprising an antibody-meditope complex; a multivalent tethering agent in combination with a monoclonal antibody or functional fragment thereof; or a combination thereof.

Claims

1. A method of purifying a monoclonal antibody or antigen-binding fragment thereof, comprising

contacting a solution containing the monoclonal antibody or antigen-binding fragment thereof with a peptide coupled to a solid support, such that a meditope binding interface of the monoclonal antibody or fragment thereof binds to the peptide, and isolating the antibody or fragment, thereby purifying the antibody or fragment,

wherein the monoclonal antibody is cetuximab, and

wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

1, 2, 5, 6, 7, 8, 21, 22, 26, 32, and 33.

2. The method of claim 1, wherein the peptide comprises the amino acid sequence of SEQ ID NO:

7 or 8.

3. The method of claim 1, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

1, 5, 6, and 22.

4. The method of claim 1, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

1, 5, 7, 8, 22, and 26.

5. The method of claim 1, wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:

5, 6, 7, 8, 21, 22, 26, 32, and 33.

6. The method of claim 1, wherein the peptide comprises the amino acid sequence of SEQ ID NO:

32.

7. A method of purifying a monoclonal antibody or antigen-binding fragment thereof, comprising:

contacting a solution containing the monoclonal antibody or antigen-binding fragment thereof with a peptide coupled to a solid support, such that a meditope binding interface of the monoclonal antibody or fragment thereof binds the peptide, and isolating the antibody or fragment, thereby purifying the antibody or fragment,

wherein the monoclonal antibody is cetuximab, and

wherein the peptide comprises the sequence of SEQ ID NO;

32.

8. A method of purifying a monoclonal antibody or antigen-binding fragment thereof, comprising

contacting a solution containing the monoclonal antibody or antigen-binding fragment thereof with a peptide coupled to a solid support, such that a meditope binding interface of the monoclonal antibody or fragment thereof binds to the peptide, and isolating the antibody or fragment, thereby purifying the antibody or fragment,

wherein the monoclonal antibody is cetuximab, and

wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

5, 6, 7, 8, 21, 22, 26, 32, and 33.