DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Acknowledgement is made of applicant’s election without traverse of the species of PI3K inhibitors. Claims 2-4, 8, 9, 11, 12, 15, 16, 18, 22, 23, 36, 37 and 48 encompass the elected specie. Claims 2-4, 8, 9, 11, 12, 15, 16, 18, 22, 23, 30-32, 34-40, and 42-48 are pending. Claims 30-32, 34, 35, 39-40 and 42-47, drawn to claims reliant on unelected species, are withdrawn from consideration. Claims 2-4, 8, 9, 11, 12, 15, 16, 18, 22, 23, 36, 37 and 48 are examined on the merits to the extent that they read on the elected species.
Claim Objections
Claims 9 and 18 are objected to because of the following informalities:
(i)the typographical error of “altered from thereof” rather than “altered form thereof” in claim 9; and
(ii)the repetition of “lung” in claim 18.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-4, 8, 9, 11, 12, 15, 16, 18, 22, 23, 37, and 48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
(A) Claims 2, 3, 37 and 48 are vague and indefinite in the recitation of a “BCR-ABL inhibitor, as provided in Table 1”. It is unclear if “as provided in Table 1” pertains to all of the c-met inhibitor, the CDK4/6 inhibitor, the PI3K inhibitor, the BRAF inhibitor the FGFR inhibitor, the Mek inhibitor and the BCR-Abl inhibitor in claims 2, 3 and 38, or both of BKM120 and in claim 37, or if “as provided in Table 1” pertains only to the BCR-ABL inhibitor in claims 2, 3, and 48 and BYL719 in claim 37.
(B)Claims 2, 3, 18, 37 and 48 rely on “Table 1” as a means for describing the metes and bounds of the claims. .
Section 2173.05(s) of the M.P.E.P. states:
Reference to Figures or Tables
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.
Thus, reliance on Table 1 in the specification renders the claims vague and indefinite.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 48 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 48 is drawn to a composition comprising an immunomodulator of an immune checkpoint in combination with a second therapeutic agent which is a PI3K inhibitor. When given the broadest reasonable interpretation the “immunomodulator” of an immune checkpoint comprises biomolecules such as antibodies, fusion proteins, and natural ligands in addition to small molecules. The PI3K inhibitor encompasses small molecules. A requirement for the composition is that it be co-formulated with both the immunomodulator and the PI3K inhibitor. As the immunomodulator encompasses the PI3K inhibitor and biomolecules, the formulation is non-trivial because it requires that the biomolecule retains its ability to inhibit or agonize a checkpoint molecule without aggregation, degradation or oxidation which results in loss of the desired activity of the immunomodulator. Further, the PI3K inhibitor must be soluble in the in the buffer of the formulation because insolubility would result in precipitation from the solution and potential aggregation and precipitation of the biomolecule. The genus of combinations of immunomodulators and PI3K inhibitors is highly variant. The specification fails to teach he co-formulation of any immunomodulator and PI3K inhibitor. Section 2163 of the MPEP states:
Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it")..
Thus, the specification fails to provide a “representative number” of members of the genus which describe the claimed genus. The specification is lacking the description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of the constituents of the composition formulation, such as buffers, pH, salts, and surfactants that show that the invention was complete, or by describing distinguishing identifying characteristics of the finished formulation sufficient to show that the inventor was in possession of the claimed invention. The specification fails to teach the requirements for a formulation that would both support biomolecules and solubilize the PI3K inhibitor, wherein both the biomolecule and the PI3K inhibitor were present at a therapeutically effective dose. One of skill in the art would reasonably conclude that applicant was not in possession of the genus of compositions of claim 48 at the time of filing
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2, 3, 4, 8, 18, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al (Proceedings of the National Academy of Science, August 12, 2014, Vol. 111, pp. 11774-11779 and Supplemental information, 7 pages, reference of the IDS filed 10/30/2023).
Claim 2 is drawn in part to a method of treating a cancer in a subject comprising administering to said subject an immunomodulator which is an inhibitor of PD-1 and an inhibitor CTLA-4 and second therapeutic agent which is a PI3K inhibitor. Claim 3 is drawn in part to a method of reducing the growth, survival or viability of a cancer cell comprising contacting said cells with an immunomodulator which is an inhibitor of PD-1 and an inhibitor CTLA-4 and second therapeutic agent which is a PI3K inhibitor. Claim 4 specifies that the immunomodulator which is a combination of an inhibitor of PD-1 and an inhibitor CTLA-4. Claim 8 requires that the inhibitor of PD-1 and CTLA-4 is an antibody. Claim 18 requires that the cancer of claim 2 is a breast tumor. Claim 23 requires that the dose of the immunomodulator in the method of claim 2 administered by injection is about 1 to 30 mg/kg.
Kim et al disclose a method for treating 4T1 tumor bearing mice with the PI3K inhibitor, J32, in combination with anti-PD-1 and anti-CTLA4 antibodies (page 11778, first column, lines 11-16 of the bottom paragraph). Which meets the limitations of claims 2, 3, 4, and 8, and claim 18 as drawn to a solid tumor from the breast. Kim et al, supplemental disclose that 10mg/kg of anti-CTLA4 and anti-PD-1 antibodies were given by the i.p. route (page 2, bridging sentence between the first and second columns) which meets the limitation of claim 23 for the immunomodulator being administered by injection at a dose of about 1 to 30 mg/kg.
Claims 2, 3, 4, 8, 9, 18, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gomez-Navarro (WO2007113648, reference of the IDS filed 10/30/2023).
Gomez-Navarro discloses a method of treatment of cancer comprising the administration of anti-CTLA4 antibodies in combination with a therapeutic agent for the treatment of cancer (abstract), wherein the therapeutic agent is an inhibitor of PI3 kinase (page 66, lines 32-33). Gomez-Navarro further discloses the administration of the anti-CTLA4 antibody resulting in CTLA4 blockade with inhibition of an immunosuppressive protein such as PD-1 further enhance anti-tumor responses provided by the anti-CTLA4 blockade (page 64, lines 17-25), which meets the requirement for an inhibitor of an immune checkpoint molecule which is CTLA4 and PD-1, and a second therapeutic agent which is a PI3 kinase inhibitor in claims 2, 3, 4; the inhibitor of the immune checkpoint being an antibody, which meets the limitation of claim 8. Gomez-Navarro discloses that the subject is preferably human (page 15, lines 32-35) which meets the limitations of claim 22. Gomez-Navarro discloses that the invention includes anti-CTLA4 antibodies with altered isotype including IgG1 and IgG4 (page 45, lines 16-31) which meets the limitation of claim 9. Disclose that cancers which are treated include
Cancers that may be treated include, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, uterine cancer, cervical cancer, prostate cancer, skin cancer, bone cancer, cancer of the small intestine, cancer of the anal region, cancer of the head or neck, gastrointestinal cancer, esophageal cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, cutaneous or intraocular melanoma, carcinoma of the endometrium, carcinoma of the vagina, carcinoma of the fallopian tubes, carcinoma of the vulva, carcinoma of the cervix, neoplasms of the central nervous system (CNS), stomach cancer, colon cancer, cancer of the rectum, renal cell carcinoma (RCC), liver cancer, kidney cancer, gastro-esophageal cancer, testicular tumor, cancer of the penis, lung carcinoma, small cell lung carcinoma (SCLC), non-small cell lung cancer (NSCLC), cancer of the urethra, cancer of the ureter, cancer of the renal pelvis, acute lymphocytic leukemia, acute myelocytic leukemia, myeloblasts leukemia, promyelocytic leukemia, myelomonocytic leukemia, monocytic leukemia, erythroleukemia, chronic leukemia, lymphocytic leukemia, chronic myeloid leukemia, chronic myelogenous leukemia, chronic myelocytic leukemia, chronic granulocytic leukemia, chronic lymphocytic leukemia, lymphocytic lymphomas, polycythemia vera, lymphoma, Hodgkin's disease lymphoma, non-Hodgkin's disease lymphoma, cutaneous T-cell lymphoma (CTCL), cutaneous B-cell lymphoma, multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease, soft tissue sarcomas, gastrointestinal stromal tumors (GIST) (line 17, page 19 to line 17, page 20) which meets the limitations of claim 18.
Claims 2, 3, 4, 8, 9, 18, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Aftab et al (WO2012/065019) as evidenced by the abstract of Yang et al ((Journal of Clinical Oncology, 2005, Vol. 23, No. 16, suppl, Abstract No. 2501).
Aftab et al disclose a method of treating a patient with anaplastic thyroid carcinoma, CLL, mantel cell lymphoma, NHL, HPV-head and neck cancer and breast cancer (claim 2 of ‘019) comprising the administration of a pharmaceutical composition comprising 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one (claim 1 of ‘019) in combination with MDX-010 (MDX-CTLA4)(claim 4 of ‘019). The abstract of Yang et al provides evidence that the MDX-010 is a human IgG1 anti-CTLA4 antibody, which meets the limitation of claim 9 for an IgG1 isotype. Afyab et al disclose that the 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one is an inhibitor of PI3K alpha (abstract), thus meeting the limitations of an inhibitor of an immune checkpoint molecule which is CTLA4, a therapeutic agent which is a PI3K inhibitor in claims 2-4; an antibody in claim 8; and the a lymphocytic leukemia, breast cancer, head and neck cancer and non-Hodgkin’s lymphoma in instant claim 18. Aftab et al disclose that patients include human patients (paragraph [0086]), which meets the limitations of claim 22.
Claims 2, 3, 4, 8, 9, 12, 16, 18, 22, and 37 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kim et al (WO2015/095404, priority to 61/917,264, page 101) as evidenced by Maecker et al (WO2013/019906, reference of the IDS filed 10/30/2023) and the abstract of Antonia et al (Journal of clinical Oncology, May 2014, Vol, 32, No. 15, abstract no. 8023).
Kim et al disclose a method for treating or delaying the progression of cancer in an individual comprising administering to the individual an effective amount of a PD-1 axis binding antagonist and a taxane (page 27, lines 2-4), in conjunction with a targeted therapy (page 68, lines 32-33), which is an inhibitor of PI3K (page 69, lines 10-12), including BKM120, CAL-101, GDC-0941, XL765, NVP-BEZ235, BGT226, and GSK2126458 (page 69, lines 13-14, 21, 34, 37-39), which meets that limitations in claims 2, 3 and 4.
. Kim et al disclose that the antagonist is a PD-1 binding antagonist, a PD-L1 binding antagonists and a PD-L2 binding antagonist (page 27, lines 6-7, which meets the limitation of administering an inhibitor of an immune checkpoint molecule which is PD-1, PD-L1 and PD-L2 in claims 2, 3 and 4. Kim et al disclose that the PD-1 axis inhibitors include antibodies (pages 27-28, bridging paragraph) which meets that limitation in claim 8 .
Kim et al disclose that the PD-1 binding antagonists include MDX-1106 (nivolumab), MK-3475(lambrolizumab), also known in the art as pembrolizumab, and CT-011 (pidilizumab), (page 3, lines 38-40) which meets the limitations of claim 8, and claim 12(a). Kim et al disclose the embodiment wherein the PD-1 axis binding antagonists is administered in combination with BKM120 (page 69, lines 12-13). The administration of BKM120 with a PD-1 axis binding inhibitors of pembrolizumab/lambrolizumab or nivolumab meets the limitation of claim 37. Kim et al disclose that the cancer which are treated include breast cancer, urothelial bladder cancer (UBC), muscle invasive bladder cancer, and BCG-refractory non-muscle invasive bladder cancer), colorectal cancer, rectal cancer, lung cancer, non-small cell lung cancer, non-Hodgkin’s lymphoma (NHL), renal cell cancer (including renal cell carcinoma), prostate cancer, liver cancer, pancreatic cancer, head and neck cancer, gastric cancer, esophageal cancer, prostate cancer, ovarian cancer, mesothelioma, and a heme malignancy, and multiple myeloma (page 4, lines 16-30) which meet the limitations of claim 18.
Kim et al disclose that an “individual” includes a human (page 20, lines 19-21), which meets the limitations of claim 22.
Regarding claim 9, the abstract of Antonia et al provides evidence that nivolumab is a human IgG4 antibody, thus, the MDX-1106 (nivolumab combination of Kim et al meets the limitations of claim 9.
Regarding claim 16, wherein the anti-PD-1 antibody comprises a heavy chain of SEQ ID NO:2 and a light chain of SEQ ID NO:3, Maecker et al provide evidence that nivolumab comprises the heavy chain of SEQ ID NO: 22 and the light chain of SEQ ID NO: 23 (paragraph [0137]) which are identical to the instant SEQ ID NO: 2 and 3:
RESULT 1
BAK33640
(NOTE: this sequence has 588 duplicates in the database searched.
See complete list at the end of this report)
ID BAK33640 standard; protein; 440 AA.
XX
AC BAK33640;
XX
DT 11-APR-2013 (first entry)
XX
DE Anti-PD-1 antibody heavy chain sequence, SEQ ID 22.
XX
KW PD-1; Programmed death 1 polypeptide; antibody; breast tumor; cancer;
KW colorectal tumor; cytostatic; heavy chain; hematological neoplasm;
KW immune stimulation; melanoma; non-small-cell lung cancer; ovary tumor;
KW pancreas tumor; renal cell carcinoma; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2013019906-A1.
XX
CC PD 07-FEB-2013.
XX
CC PF 01-AUG-2012; 2012WO-US049233.
XX
PR 01-AUG-2011; 2011US-0574406P.
XX
CC PA (GETH ) GENENTECH INC.
CC PA (HOFF ) HOFFMANN LA ROCHE&CO AG F.
XX
CC PI Maecker H, Irving B;
XX
DR WPI; 2013-B87383/14.
XX
CC PT Treating or delaying progression of cancer e.g. melanoma and pancreatic
CC PT cancer, comprises administering a programmed cell death protein 1 axis
CC PT binding antagonist e.g. pidilizumab, and a mitogen-activated protein
CC PT kinase kinase inhibitor.
XX
CC PS Disclosure; SEQ ID NO 22; 127pp; English.
XX
CC The present invention relates to a novel method for treating or delaying
CC progression of cancer in an individual. The method involves administering
CC a programmed death 1 polypeptide (PD-1) axis binding antagonist and a MEK
CC inhibitor, to the individual. The invention also provides: a method for
CC enhancing immune function in an individual having cancer; and a kit
CC comprising a PD-1 axis binding antagonist and a package insert comprising
CC instructions for using the PD-1 axis binding antagonist and the MEK
CC inhibitor, for treating or delaying progression of cancer. The cancer is
CC chosen from colorectal cancer, melanoma, non-small cell lung cancer,
CC ovarian cancer, breast cancer, pancreatic cancer, hematological
CC malignancy or renal cell carcinoma, wherein the cancer contains a BRAF
CC V600E mutation, a KRAS wild-type and an activating KRAS mutation. The
CC present sequence represents an anti-PD-1 antibody heavy chain, which can
CC be used for treating or delaying the progression of above mentioned
CC cancer in an individual.
XX
SQ Sequence 440 AA;
Query Match 100.0%; Score 2348; Length 440;
Best Local Similarity 100.0%;
Matches 440; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY 60
Qy 61 ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS 120
Qy 121 VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS 180
Qy 181 VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP 240
Qy 241 KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT 300
Qy 301 VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC 360
Qy 361 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV 420
Qy 421 MHEALHNHYTQKSLSLSLGK 440
||||||||||||||||||||
Db 421 MHEALHNHYTQKSLSLSLGK 440
RESULT 1
BAK33641
(NOTE: this sequence has 814 duplicates in the database searched.
See complete list at the end of this report)
ID BAK33641 standard; protein; 214 AA.
XX
AC BAK33641;
XX
DT 11-APR-2013 (first entry)
XX
DE Anti-PD-1 antibody light chain sequence, SEQ ID 23.
XX
KW PD-1; Programmed death 1 polypeptide; antibody; breast tumor; cancer;
KW colorectal tumor; cytostatic; hematological neoplasm; immune stimulation;
KW light chain; melanoma; non-small-cell lung cancer; ovary tumor;
KW pancreas tumor; renal cell carcinoma; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2013019906-A1.
XX
CC PD 07-FEB-2013.
XX
CC PF 01-AUG-2012; 2012WO-US049233.
XX
PR 01-AUG-2011; 2011US-0574406P.
XX
CC PA (GETH ) GENENTECH INC.
CC PA (HOFF ) HOFFMANN LA ROCHE&CO AG F.
XX
CC PI Maecker H, Irving B;
XX
DR WPI; 2013-B87383/14.
XX
CC PT Treating or delaying progression of cancer e.g. melanoma and pancreatic
CC PT cancer, comprises administering a programmed cell death protein 1 axis
CC PT binding antagonist e.g. pidilizumab, and a mitogen-activated protein
CC PT kinase kinase inhibitor.
XX
CC PS Disclosure; SEQ ID NO 23; 127pp; English.
XX
CC The present invention relates to a novel method for treating or delaying
CC progression of cancer in an individual. The method involves administering
CC a programmed death 1 polypeptide (PD-1) axis binding antagonist and a MEK
CC inhibitor, to the individual. The invention also provides: a method for
CC enhancing immune function in an individual having cancer; and a kit
CC comprising a PD-1 axis binding antagonist and a package insert comprising
CC instructions for using the PD-1 axis binding antagonist and the MEK
CC inhibitor, for treating or delaying progression of cancer. The cancer is
CC chosen from colorectal cancer, melanoma, non-small cell lung cancer,
CC ovarian cancer, breast cancer, pancreatic cancer, hematological
CC malignancy or renal cell carcinoma, wherein the cancer contains a BRAF
CC V600E mutation, a KRAS wild-type and an activating KRAS mutation. The
CC present sequence represents an anti-PD-1 antibody light chain, which can
CC be used for treating or delaying the progression of above mentioned
CC cancer in an individual.
XX
SQ Sequence 214 AA;
Query Match 100.0%; Score 1106; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Thus, the MDX-1106 (nivolumab combination of Kim et al meets the limitations of claim 16.
Claims 2-4, 8, 9, 11, 12, 18, 22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Liang et al (WO2016/028672, priority to 62/039,081, page 159 and reference of the IDS filed 10/30/2023).
Liang et al disclose methods for treating cancer in a subject comprising the administration of anti-LAG3 antibodies to the subject for treatment (page 82, lines 2-34). Liang et al disclose that that the anti-LAG3 antibodies of the invention are antagonistic antibodies (page 8, lines 15-18). Liang et al disclose that the anti-LAG3 antibodies are used in association with a therapeutic agent including an inhibitor of PI3K (page 107, line 20). Thus, the administration of the anti-LAG3 antibodies in association with inhibitors of PI3K meet the limitations of claims 2, 3, 4, 8, and 12. Liang et al disclose that osteosarcoma, rhabdomyosarcoma, neuroblastoma, kidney cancer, leukemia, renal transitional cell cancer, bladder cancer, Wilm's cancer, ovarian cancer, pancreatic cancer, breast cancer, prostate cancer, bone cancer, lung cancer, gastric cancer, colorectal cancer, cervical cancer, synovial sarcoma, head and neck cancer, squamous cell carcinoma, multiple myeloma, renal cell cancer, hepatocellular carcinoma, melanoma, endometrial cancer, liver cancer, breast cancer or gastric cancer is treated by administering to the subject an effective amount of an anti-LAG3 antibody, in association with a further therapeutic agent (page 12, lines 10-24) which meet the limitations of claim 18. Liang et al disclose than the subject being treated include human subjects (page 82, lines 29-34) which meets the limitations of claim 22. Liang et al disclose that the anti-LAG3 antibodies of the invention include bispecific and bifunctional antibodies and antigen-binding fragments having a binding specificity for LAG3 and PD-1 or PD-L1, and methods of use thereof (page 68, lines 3-5) thus meeting the limitation of claim 11 wherein the bispecific antibody has a first binding specificity to PD-1 or PD-L1 and a second binding specificity to LAG3..
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2, 3, 4, 8, 9, 12, 16, 18, 22, 23, 36 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO2015/095404, priority to 61/917,264, page 101) as evidenced by Maecker et al (WO2013/019906) and the abstract of Antonia et al (Journal of clinical Oncology, May 2014, Vol, 32, No. 15, abstract no. 8023), in view of Burger et al (ACS Medicinal chemistry, 2011, Vol. 2, pp. 774-779).
Claim 36 requires, in part, that nivolumab in the method of claim 2 is administered with a PI3K inhibitor having the specific heterocyclic structure. Claim 37 requires, in part, that the nivolumab in the method of claim 2 is administered with BKM120.
The teachings of Kim et al provide for a method for treating or delaying the progression of cancer in an individual comprising administering to the individual an effective amount of a PD-1 axis binding antagonist and a taxane, wherein the PD-1 axis binding antagonist is an antagonist of PD-1, PD-L1 or PD-L2 in conjunction with an inhibitor of PI3K, wherein the PD-1 antagonist is nivolumab, lambrolizumab/pembrolizumab, or pidilizumab for the reasons set forth above. Kim et al do not specifically teach that the inhibitor of PI3K is NVP-BKM120.
Burger et al teach NVP-BKM120, otherwise known as BKM120, as a potent, selective and orally bio-available PI3 kinase inhibitor for the treatment of cancer (Title). Burger et al teach that NVP-BKM120 displays a well-tolerated in vivo activity across a range of PI3K pathway deregulated tumor xenograft models when orally administered as well as exhibiting high permeability and lack of efflux (page 777, second column, 2nd full paragraph). Burger et al teach that NVP-BKM120 has favorable cellular potency, kinase selectivity, clinical pharmacology and pharmacokinetics (page 778, first column, 2nd full paragraph). Burger et al teach that NVP-BKM120 has shown clinical activity in patients with cancer (page 778, first column, 2nd full paragraph).
It would have been prima facie obvious at the time prior to the effective filing date to use NVP-BKM120 as the PI3K inhibitor in the method of treating cancer of Kim et al. One of skill in the art would have been motivated to do so by the teachings of Burger et al regarding the favorable cellular potency, kinase selectivity, clinical pharmacology and pharmacokinetics, high permeability and lack of efflux, and clinical activity in patients with cancer
Claims 2-4, 8, 9, 11, 12, 15, 18, 22, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al (WO2016/028672) in view of Woo et al (Cancer Research, 2011, Vol. 72, pp. 917-927, reference of the IDS filed 10/30/2023) and (Korman et al (WO2015/042246, reference of the IDS filed 10/30/2023).
Claim 15 requires that the anti-LAG3 antibody of clam 12 is BMS-986016.
Liang et al teach the administration of anti-LAG3 antibodies in association with inhibitors of PI3K for the treatment of cancer in a subject.
Liang et al do not specifically teach that the anti-LAG3 is BMS-986016 or that the anti-PD-1 antibody is injected at a dose of about 1-30mg/kg, required in claim 23..
Woo et al teach that LAG3 and PD-1 synergistically regulate T cell function to promote tumoral immune escape (Title). Woo et la teach mouse xenograft models, SaIN, and MC38 inoculated mice were injected with a dose of 10mg/kg anti-PD-1 and/or anti-LAG3 (pp. 918-919, bridging paragraph), which meets the limitation of claim 23 . Woo et al teach that 70% and 80% of the mice, respectively, were tumor-free after 50 days following combinatorial anti-LAG3 and anti-PD-1 immunotherapy (page 919, lines 24-27 under the heading “Combinatorial anti-LAG3/anti-PD-1 …”). Woo et al teach that high level dual LAG3/PD1 expression is largely restricted to infiltrating TILs, and thus combinatorial immunotherapy with antio-LAG3 and anti-PD1 may promote tumor-specific responses which would be less toxic than CTLA-4 blockade(final paragraph). Woo et al conclude that the combined anti-LAG3/anti-PD1 blockade is a highly promising combinatorial strategy for the immune base therapy of caner (final sentence).
Korman et al teach method of treating solid tumors in a human patient comprising administering a combination of a LAG3 antibody and a antri-PD-1 antibody (page 3, lines 1-6 under “Summary”). Korman et al teach the anti-LAG3 antibody BMS-986016 combined with the anti-PD-1 antibody of BMS-936558 (pages 3-4, bridging paragraph). Korman et al teach pre-clinical testing of monkeys, wherein the combination therapy was generally well-tolerated and clinical signs of toxicity were observed in only one out of 9 monkeys (page 30, lines 5 and 6 of the bottom paragraph)
It would have been prima facie obvious at the time prior to the effective filing date to use BMS-986016 as the anti-LAG3 antibody and BMS-936558 as the anti-PD-1 antibody in the method of Liang et al wherein anti-LAG3 antibodies in association with inhibitors of PI3K are administered for the treatment of cancer in a subject. One of skill in the art would have been motivated to combine the anti-PD-1 antibody with the anti-LAG3 antibody of Liang by the teachings of Woo et al on the inhibition of tumor growth by the combined administration of anti-LAG3 and anti-PD1 antibodies. One of skill in the art would have been motivated to use the BMS-986016 as the anti-LAG3 antibody and BMS-936558 as the anti-PD-1 antibody by the teachings of Korman et al on the pre-clinical testing of monkeys, wherein the combination therapy was generally well-tolerated and clinical signs of toxicity were observed in only one out of 9 monkeys.
All claims are rejected.
Please note that WO2012/065019 and WO2015/095404 could not be attached to the Office action due to technical difficulties and will be provided to applicant as soon as the technical difficulties are resolved.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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