Claims for Patent: 10,238,742
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Summary for Patent: 10,238,742
Title: | Cell penetrating nucleolytic antibody based cancer therapy |
Abstract: | Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A sub-set of autoantibodies having nucleolytic activity are capable of nuclear penetration. These antibodies can be used as therapeutic agents targeted towards DNA repair-deficient malignancies. |
Inventor(s): | Hansen; James E. (Guilford, CT), Weisbart; Richard H. (Los Angeles, CA), Noble; Philip W. (New Haven, CT) |
Assignee: | Yale University (New Haven, CT) The United States of America as Represented by the Department of Veterans Affairs (Washington, DC) |
Application Number: | 14/750,683 |
Patent Claims: | 1. A pharmaceutical composition comprising a) a cell-penetrating, nucleolytic antibody, or antigen binding fragment thereof, comprising: a heavy chain variable region comprising
respectively the first, second, and third complementarity determining regions (CDRs) of SEQ ID NO:5 or humanized variants thereof, and a light chain variable region comprising respectively the first, second, and third CDRs of SEQ ID NO:1 or humanized
variants thereof, in a unit dosage between about 0.01 and about 100 mg/kg body weight of a human; and b) a pharmaceutically acceptable excipient for injection.
2. The pharmaceutical composition of claim 1, further comprising one or more antineoplastic or radio-sensitizing agents selected from the group consisting of cisplatin, cytoxan, doxorubicin, methotrexate, mitomycin c, nitrogen mustard, hydroxyurea, bevacizumab, cetuximab, rituximab, trastuzumab, tirapazamine, temozolomide, camptothecin, cisplatin, gemcitabine, 5-fluorouracil, hydroxyurea, pentoxifylline, vinorelbine, and combinations thereof. 3. The pharmaceutical composition of claim 1, in the unit dosage form for intravenous injection or intratumoral injection. 4. The pharmaceutical composition of claim 1, wherein the antibody or antigen binding fragment thereof, is a monovalent or multivalent single chain variable fragment (scFv). 5. The pharmaceutical composition of claim 1, wherein the first light chain CDR comprises the amino acid sequence of SEQ ID NO:2; the second light chain CDR comprises the amino acid sequence of SEQ ID NO:3; the third light chain CDR comprises the amino acid sequence of SEQ ID NO:4; the first heavy chain CDR comprises the amino acid sequence of SEQ ID NO:6; the second heavy chain CDR comprises the amino acid sequence of SEQ ID NO:7; and the third heavy chain CDR comprises the amino acid sequence of SEQ ID NO:8. 6. The pharmaceutical composition of claim 1, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:1 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5. 7. The pharmaceutical composition of claim 1, wherein the antibody or antigen binding fragment thereof, is a humanized antibody or an antigen binding fragment thereof. 8. The pharmaceutical composition of claim 7, wherein the first light chain CDR comprises the amino acid sequence of SEQ ID NO:2; the second light chain CDR comprises the amino acid sequence of SEQ ID NO:3; the third light chain CDR comprises the amino acid sequence of SEQ ID NO:4; the first heavy chain CDR comprises the amino acid sequence of SEQ ID NO:6; the second heavy chain CDR comprises the amino acid sequence of SEQ ID NO:7; and the third heavy chain CDR comprises the amino acid sequence of SEQ ID NO:8. 9. The pharmaceutical composition of claim 1, wherein the antibody or antigen binding fragment thereof, is a chimeric antibody. 10. The pharmaceutical composition of claim 9, wherein the first light chain CDR comprises the amino acid sequence of SEQ ID NO:2; the second light chain CDR comprises the amino acid sequence of SEQ ID NO:3; the third light chain CDR comprises the amino acid sequence of SEQ ID NO:4; the first heavy chain CDR comprises the amino acid sequence of SEQ ID NO:6; the second heavy chain CDR comprises the amino acid sequence of SEQ ID NO:7; and the third heavy chain CDR comprises the amino acid sequence of SEQ ID NO:8. 11. The pharmaceutical composition of claim 10, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:1 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5. 12. The pharmaceutical composition of claim 1, wherein the antibody or antigen binding fragment thereof, is not an IgG2a-k mouse monoclonal antibody. |
Details for Patent 10,238,742
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Genentech, Inc. | RITUXAN | rituximab | Injection | 103705 | 11/26/1997 | ⤷ Try a Trial | 2034-06-25 |
Genentech, Inc. | HERCEPTIN | trastuzumab | For Injection | 103792 | 09/25/1998 | ⤷ Try a Trial | 2034-06-25 |
Genentech, Inc. | HERCEPTIN | trastuzumab | For Injection | 103792 | 02/10/2017 | ⤷ Try a Trial | 2034-06-25 |
Eli Lilly And Company | ERBITUX | cetuximab | Injection | 125084 | 02/12/2004 | ⤷ Try a Trial | 2034-06-25 |
Eli Lilly And Company | ERBITUX | cetuximab | Injection | 125084 | 03/28/2007 | ⤷ Try a Trial | 2034-06-25 |
Genentech, Inc. | AVASTIN | bevacizumab | Injection | 125085 | 02/26/2004 | ⤷ Try a Trial | 2034-06-25 |
Genentech, Inc. | RITUXAN HYCELA | rituximab and hyaluronidase human | Injection | 761064 | 06/22/2017 | ⤷ Try a Trial | 2034-06-25 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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