# US 8,771,932 B2 · Rationally designed antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,771,932 B2 - Document ID: US8771932B2 - Status: Granted - Kind: B2 - Application number: 12/321,828 - Filed: 2009-01-26 - Published: 2010-02-18 - Granted: 2014-07-08 - Earliest claimed: 2000-12-05 - Assignees: Alexion Pharmaceuticals, Inc. - Applicants: Katherine S. Bowdish; Mark Renshaw; Shana Frederickson - Inventors: Katherine S. Bowdish; Mark Renshaw; Shana Frederickson - Web page: https://patentgrep.com/patent/US8771932B2 ## CPC - C07K 14/505: Erythropoietin [EPO] - C07K 14/524: {Thrombopoietin, i.e. C-MPL ligand} - C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies - C07K 16/005: {constructed by phage libraries} - C07K 16/1282: Clostridium (G) - C07K 16/18: against material from animals or humans - C07K 16/46: Hybrid immunoglobulins (hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00) - C12N 5/0641: {Erythrocytes} - A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) - A61K 39/40: bacterial - A61K 2039/505: {comprising antibodies} - C07K 2317/21: from primates, e.g. man - C07K 2317/55: Fab or Fab' - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/74: Inducing cell proliferation - C07K 2318/10: Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes - C07K 2319/00: Fusion polypeptide - C07K 2319/036: targeting to the medium outside of the cell, e.g. type III secretion - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - C07K 2319/75: containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones - C12N 2501/14: Erythropoietin [EPO] - C12N 2506/11: from blood or immune system cells - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Antibodies or fragments thereof having CDR regions replaced or fused with biologically active peptides are described. Flanking sequences may optionally be attached at one or both the carboxy-terminal and amino-terminal ends of the peptide in covalent association with adjacent framework regions. Compositions containing such antibodies or fragments thereof are useful in therapeutic and diagnostic modalities. ## Claims ### Claim 1 A method of stimulating proliferation, differentiation, or growth of promegakaryocytes or megakaryocytes, comprising contacting promegakaryocytes or megakaryocytes with an effective amount of an immunoglobulin molecule or fragment thereof comprising one or more thrombopoietin (TPO) mimetic peptides, wherein: a) said one or more TPO mimetic peptides replace at least a portion of one or more complementarity determining regions (CDRs) or b) said one or more TPO mimetic peptides are fused to one or more CDRs, wherein said immunoglobulin molecule or fragment thereof comprising the one or more TPO mimetic peptides binds to a TPO receptor, and wherein said immunoglobulin or fragment thereof comprising one or more TPO mimetic peptides comprises one or more immunoglobulin framework regions. ### Claim 2 (depends on 1) The method according to claim 1, wherein platelet production is increased. ### Claim 3 (depends on 1) The method according to claim 1, wherein the TPO mimetic peptide is selected from the group consisting of SEQ. ID. NO: 31, SEQ. ID. NO: 35, SEQ. ID. NO: 37, SEQ. ID. NO: 39, SEQ. ID. NO: 41, SEQ. ID. NO: 43, SEQ. ID. NO: 45, and SEQ. ID. NO: 49. ### Claim 4 (depends on 1) The method according to claim 1, wherein the immunoglobulin molecule or fragment thereof comprising one or more TPO mimetic peptides further comprises at least one flanking amino acid residue covalently linked to at least one end of a TPO mimetic peptide. ### Claim 5 (depends on 4) The method of claim 4, wherein the at least one flanking amino acid residue includes a proline that is covalently linked to the TPO mimetic peptide. ### Claim 6 (depends on 1) The method according to claim 1, wherein at least a portion of at least two CDRs are replaced with a TPO mimetic peptide. ### Claim 7 (depends on 1) The method according to claim 1, wherein the immunoglobulin molecule comprising one or more TPO mimetic peptides is produced by replacing at least a portion of one or more CDRs of a full IgG molecule with one or more TPO mimetic peptides, or by fusing one or more TPO mimetic peptides to one or more CDRs of a full IgG molecule. ### Claim 8 (depends on 1) The method according to claim 1, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are located on a light chain. ### Claim 9 (depends on 1) The method according to claim 1, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are located on a heavy chain. ### Claim 10 (depends on 1) The method according to claim 1, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are selected from the group consisting of a CDR3 of a heavy chain and a CDR2 of a light chain. ### Claim 11 (depends on 1) The method according to claim 1, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are selected from the group consisting of a CDR3 of a heavy chain and a CDR2 of a heavy chain. ### Claim 12 (depends on 1) The method according to claim 1, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are selected from the group consisting of a CDR3 of a heavy chain and a CDR1 of a light chain. ### Claim 13 (depends on 1) The method according to claim 1, wherein at least one full-length CDR is replaced with a TPO mimetic peptide. ### Claim 14 (depends on 1) The method according to claim 1, wherein at least a portion of a CDR3 of a heavy chain and at least a portion of a CDR3 of a light chain are each replaced with a TPO mimetic peptide. ### Claim 15 (depends on 1) The method of claim 1, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides include both CDR2 and CDR3. ### Claim 16 (depends on 15) The method of claim 15, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are located in a heavy chain. ### Claim 17 (depends on 15) The method of claim 15, wherein the one or more CDRs that are replaced with one or more TPO mimetic peptides are located in a light chain. ### Claim 18 (depends on 1) The method according to claim 1, wherein the immunoglobulin molecule or fragment thereof comprising one or more TPO mimetic peptides is produced by replacing at least a portion of one or more CDRs of a human or humanized immunoglobulin molecule or fragment thereof with one or more TPO mimetic peptides, or by fusing one or more TPO mimetic peptides to one or more CDRs of a human or humanized immunoglobulin molecule or fragment thereof. ### Claim 19 (depends on 18) The method according to claim 18, wherein the human or humanized immunoglobulin molecule or fragment thereof is an anti-tetanus toxoid immunoglobulin or fragment thereof. ### Claim 20 (depends on 1) The method of claim 1, wherein said immunoglobulin or fragment thereof comprising one or more TPO mimetic peptides is produced by replacing at least a portion of one or more CDRs of a parent immunoglobulin molecule or fragment thereof with one or more TPO mimetic peptides, or by fusing one or more TPO mimetic peptides to one or more CDRs of a parent immunoglobulin molecule or fragment thereof, wherein said parent immunoglobulin molecule or fragment thereof is selected from the group consisting of a Fab, a F(ab′)2, an scFv, a Fv, a heavy chain variable region, and a light chain variable region.