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 .
Detailed Action
Claims 1, 7-8, 11, 20 and 22 have been amended. Claims 1, 4-5, 7-11, 13, 18, 20 and 22-23 are pending and are now evaluated on its merits.
Priority
This application claims foreign benefit to application CN202010722483.1, dated 07/24/2020.
Response to Arguments
Applicant’s arguments, see Pages 2-4, filed 07/08/2026, with respect to the rejection(s) of claims 1, 4-5, 7-11, 13, 18, 20 and 22-23 under Cai et al. (WO 2012130166 A1) in view of Wang et al. (WO 2019015561 A1) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Cai et al. (WO 2012130166 A1) in view of Van Erp et al. Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo, J Cancer Res Clin Oncol, April 2020, Pages 1659-1670 and Xu et al. (CN 105461697 A).
The teachings of Cai from the previous office action in view of Van Erp of the treatment of desmoplastic small round cell tumors comprising the combination treatment of the PARP inhibitor Olaparib at 25mg with temozolomide at 25mg for 28 days and the teachings of Xu for the treatment of cancer comprising the combination of a PARP inhibitor and temozolomide read to the limitations of claimed invention.
Additionally, as per previous office action applicant has not provided unexpected results from administration of the combination treatment over the claimed consecutive 28-day and 21-day regimen as compared to 1 week or less treatment within the claimed concentration range. According to applicants’ specification (page 29) administration of the composition to be effective can be for at least 7, 14, 21 or 28 consecutive days.
Claim Rejections - 35 USC § 112
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.
Claims 1, 4-5, 7-9 and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the tumors listed on page 5, last paragraph to page 6, first paragraph of applicant’s specification, does not reasonably provide enablement for all cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
(A) The breadth of the claims; [AltContent: rect]
(B) The nature of the invention; [AltContent: rect]
(C) The state of the prior art; [AltContent: rect]
(D) The level of one of ordinary skill; [AltContent: rect]
(E) The level of predictability in the art; [AltContent: rect]
(F) The amount of direction provided by the inventor; [AltContent: rect]
(G) The existence of working examples; and [AltContent: rect]
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Undue experimentation is required by one skilled in the art to determine enablement of the instant disclosure as claimed due to the following:
(A) The breadth of the claims and (B) The nature of the invention
The nature of the invention and breadth of the claims is the treatment of cancer (claim 1). Applicants’ specification does not define treatment; thus, the broadest reasonable interpretation includes a patient population of everyone.
(C) The state of the prior art and (E) The level of predictability in the art
Applicant is enabled for the cancers the encompass the treatment with PARP Inhibitor of Formula III
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and temozolomide (TMZ), in which TMZ is known to be used in treatments of are gliomas, melanoma, lung cancer, breast cancer, lymphoma, gastric cancer and others include on page 26 of applicant’s specification.
(F) The amount of direction provided by the inventor and (G) The existence of working examples
Applicant’s specification provides examples of inhibitor IMP4297 with TMZ for small cell lung cancer NCI-H209 cells (Table 1) and a Phase IB/II clinical trail of IMP4297 with TMZ for patients with pancreatic, endometrial, ovarian, mesothelioma, SCLC, rectal and peripheral nerve sheath cancers. The specification provides enablement for the cancers listed and not enabled for all cancers.
(D) The level of one of ordinary skill and (H) The quantity of experimentation needed
The skill level of ordinary skill in the art is of an M.D or Ph.D. due to the complexity of the cancer lines being treated and the configuration and testing of the claimed compounds. With the provided experimental evidence provided one skilled in the art would not be able to determine the treatment of all cancers from the administration of Formula III and TMZ.
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.
Claims 1, 4-5, 7-10 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. (WO 2012130166 A1) in view of Van Erp et al. Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo, J Cancer Res Clin Oncol, April 2020, Pages 1659-1670 and Xu et al. (CN 105461697 A).
Regarding claims 1, 4-5, 7-10 and 23, Cai teaches a method for the treatment of cancers of the liver, melanoma, Hodgkin's disease, non-Hodgkin's lymphoma, acute lymphocytic leukemia, chronic lymphocytic leukemia, soft-tissue sarcoma, multiple myeloma, neuroblastoma, breast carcinoma, ovarian carcinoma, lung carcinoma, Wilms' tumor, cervical carcinoma (relevant to claim 10) (para. 0057) comprising a PARP inhibitor of Formula I, II or III in combination with at least one anticancer agent selected from cyclophosphamide, ifosfamide, temozolomide, bendamustine and cis-platin (para. 0061).
Cai teaches formula I:
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(relevant to claim 1). Formula II:
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(relevant to claim 2). Formula III:
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(relevant to claim 4) (para. 0013-0018). Cai additionally teaches preferred compounds of Formulae I, II and III include, without limitation majority of the compounds of claim 5 of claimed invention (para. 0019) which includes 7-Fluoro- 1 -(3 -(4-(pyrimidin-2-yl)piperazine- 1 -carbonyl)benzyl)quinazoline-2,4( 1Η, 3Η)- dione and 5-Fluoro-1-(4-fluoro-3 -(4-(pyridin-2-yl)piperazine- 1 -carbonyl)benzyl)quinazoline- 2,4(lH,3H)-dione; (relevant to claims 5) (para. 0019).
Cai additionally teaches the compounds may be administered to mammals, orally at a dose of 0.0025 to 50 mg/kg of body weight, per day, and when the known anticancer agent is also administered, it is administered in an amount that is effective to achieve its intended purpose. The amounts of such known anticancer agents effective for cancer are well known to those skilled in the art (para. 0066). For topical formulation, the compound may be present at a concentration of approximately 0.01 to 100 mg per gram of carrier (relevant to claims 7-9 and 23) (para. 0068).
Cai fails to teach the temozolomide at a daily dose of 10-30 mg and the composition administered for one cycle of 28 days of the claimed compound and 21 days of temozolomide.
Van Erp teaches the treatment of desmoplastic small round cell tumors, a soft-tissue sarcoma, comprising the combination treatment of the PARP inhibitor Olaparib and with temozolomide (abstract). In a mouse sample Van Erp teaches temozolomide and Olaparib administered at 25mg each for 7 days over a 28-day cycle, in which tumor volume was reduced at day 10 (fig. 4). Additionally, the combination treatment showed synergy when administered a lower dosage compared to higher individual dosages (figure 2).
Xu teaches the treatment of tumors comprising a synergistic combination of the PARP inhibitor
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and temozolomide. Of particular embodiment Xu teaches the anti-tumor effect for breast cancer of the combination treatment wherein the compound is administered at 25mg and temozolomide at 25 mg continuously for 8 days, once per day (Table 4, para. 0517).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filing to have administered the composition of the PARP inhibitor of formula III and temozolomide taught by Cai at the dosage amount and consecutive days of claimed invention to treat cancer. One would have been motivated to do so from the teachings of Cai of formula III administered at a dosage amount within the claimed dosage range in combination with temozolomide with the teachings of Van Erp and Xu of the synergistic combination of the PARP inhibitors taught by Cai and temozolomide administered at 25mg each for consecutive days. Thus, treatment for 28 consecutive days of claimed compound along with 21 consecutive days of temozolomide is obvious to the above reasoning as the testing of continuous days until treatment is observed is of routine experimentation as per MPEP 2144.05 (II): "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 11, 13, 18, 20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. (WO 2012130166 A1) in view of Van Erp et al. Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo, J Cancer Res Clin Oncol, April 2020, Pages 1659-1670, Xu et al. (CN 105461697 A) and Yoshioka et. al. "Stability of Drugs and Dosage Forms" Kluwer Academic Publishers, New York 2002, page 175 section 4.3.
The teachings of Cai, Van Erp and Xu from the above 103 rejection of claims 1, 4-5, 7-10 and 23 are incorporated herein by reference.
Cai, Van Erp and Xu fail to teach the combination treatment of a PARP inhibitor and temozolomide as a packaged kit.
Yoshioka teaches packaging plays an essential role in the stability of a product. The process of packaging is to protect the dosage forms from moisture and oxygen present in the atmosphere, light, and other types of exposure, especially if these factors affect the overall quality of the product on long-term storage (Pg. 175, section 4.3).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have packaged the claimed compound and temozolomide as a kit. One would have been motivated to do so because Yoshioka teaches the process of packaging plays an essential role in the stability of the product and its shelf life for long term storage. Thus, one of ordinary skill in the art would package the combination treatment taught by Cai to protect the product when stored and preserve the stability.
Conclusion
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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