# US 2010/0166746 A1 · High potency recombinant antibodies, methods for producing them and use in cancer therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0166746 A1 - Document ID: US20100166746A1 - Status: Published application - Kind: A1 - Application number: 12/517,300 - Filed: 2007-12-04 - Published: 2010-07-01 - Earliest claimed: 2006-12-04 - Assignees: Medlmmune Way - Inventors: Partha Chowdhury; Herren Wu; Laura Richman - Web page: https://patentgrep.com/patent/US20100166746A1 ## CPC - C07K 16/005: {constructed by phage libraries} - A61P 35/00: Antineoplastic agents - C07K 16/2866: {against receptors for cytokines, lymphokines, interferons} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention contemplates improved recombinant anti-tumor antibodies having faster Kon and faster Koff rates, resulting in a uniform tumor penetrance, as compared to the same recombinant anti-tumor antibody without said faster Kon and faster Koff rates, and methods of improving the same. ## Claims ### Claim 1 A method of improving a recombinant anti-tumor antibody's penetrance into a targeted tumor, comprising: (a) increasing the Kon rate by at least 2 fold as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate; and (b) achieving a uniform tumor penetrance by said improved recombinant anti-tumor antibody into said targeted tumor as measured by immunohistochemistry staining (IHC) as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate and demonstrates a non-uniform or patchy staining as measured by IHC. ### Claim 2 (depends on 1) The method of claim 1, wherein said method further comprises after step (a), a step of increasing the Koff rate by at least 2 fold as compared to the same recombinant anti-tumor antibody without such an increase in Koff rate. ### Claim at position 3 -4. (canceled) ### Claim 5 (depends on 1) The method of claim 1, wherein said uniform tumor penetrance by said improved recombinant anti-tumor antibody into said targeted tumor demonstrates at least 70% IHC staining. ### Claim at position 5 -8. (canceled) ### Claim 9 A method of improving a recombinant anti-tumor antibody's penetrance into a targeted tumor, comprising: (a) increasing the Kon rate by at least 2 fold as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate; and (b) achieving an intra-tumoral diffusion greater than 3 tumor cell diameters as measured by IHC, as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate and demonstrates an intra-tumoral diffusion of 3 or less tumor cell diameters as measured by IHC. ### Claim 10 (canceled) ### Claim 11 (depends on 1) The method of claim 1, wherein said improved recombinant anti-tumor antibody specifically binds to targets CD20, HER2/neu, VEGF, EphA2, integrin αvβ3, EphA4, CD2, CD19, CD22, cMET, ALK, DLL4, or CEA. ### Claim 12 (depends on 9) The method of claim 9, wherein said improved recombinant anti-tumor antibody specifically binds to targets CD20, HER2/neu, VEGF, EphA2, integrin avβ3, EphA4, CD2, CD19, CD22, cMET, ALK, DLL4, or CEA. ### Claim 13 (depends on 1) The method of claim 1, wherein said improved recombinant anti-tumor antibody has a Kon rate of at least 104 M−1s−1 or greater. ### Claim 14 (depends on 9) The method of claim 9, wherein said improved recombinant anti-tumor antibody has a Kon rate of at least 104 M−1s−1 or greater. ### Claim 15 (depends on 1) The method of claim 1, wherein said improved recombinant anti-tumor antibody has a Koff rate of 10−3 s−1 or less. ### Claim 16 (depends on 9) The method of claim 9, wherein said improved recombinant anti-tumor antibody has a Koff rate of 10−3 s−1 or less. ### Claim at position 14 -22. (canceled) ### Claim 23 A recombinant anti-tumor antibody having improved tumor penetrance into a targeted tumor, produced by a method comprising: (a) increasing the Kon rate by at least 2 fold as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate; and (b) achieving a uniform tumor penetrance by said improved recombinant anti-tumor antibody into said targeted tumor as measured by immunohistochemistry staining (IHC) as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate and demonstrates a non-uniform or patchy staining as measured by IHC. ### Claim 24 A recombinant anti-tumor antibody having improved tumor penetrance into a targeted tumor, produced by a method comprising: (a) increasing the Kon rate by at least 2 fold as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate; and (b) achieving an intra-tumoral diffusion greater than 3 tumor cell diameters as measured by IHC, as compared to the same recombinant anti-tumor antibody without such an increase in Kon rate and demonstrates an intra-tumoral diffusion of 3 or less tumor cell diameters as measured by IHC. ### Claim at position 17 -50. (canceled) ### Claim 51 (depends on 23) A composition comprising, the recombinant anti-tumor antibody having improved tumor penetrance of claim 23, and a pharmacologically acceptable diluent or excipient. ### Claim 52 (depends on 51) A method of treating a tumor in a patient in need thereof, comprising administering a therapeutically effective amount of the composition of claim 51. ### Claim 53 (depends on 24) A composition comprising, the recombinant anti-tumor antibody having improved tumor penetrance of claims 24, and a pharmacologically acceptable diluent or excipient. ### Claim 54 (depends on 53) A method of treating a tumor in a patient in need thereof, comprising administering a therapeutically effective amount of the composition of claim 53.