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 .
Election/Restrictions
Regarding the election of species requirement, Applicants elected, without traverse, the
following species for examination:
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Applicant's election without traverse of the above species in the reply filed on 10 June 2026 is acknowledged.
Applicant is reminded that, upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional corresponding species which are written in dependent form or otherwise require all the limitations of an allowed generic claim. With regard to Species Groups A and B, in view of the most recently entered amendments to the claims, no claim is currently generic to those Species Groups. With regard to Species Group C, the following elected claim is currently generic with respect to the elected species: Claim 1.
However, no generic claim has been found allowable. See rejections below.
The election species requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1 and 6-9 are pending.
Priority
The instant application claims priority as follows:
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Information Disclosure Statement
An IDS has not been received.
Claim Rejections - 35 USC § 103
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.
The framework for the objective analysis for determining obviousness under 35 U.S.C. 103 is stated in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Obviousness is a question of law based on underlying factual inquiries. The factual inquiries enunciated by the Supreme Court in Graham are summarized as follows:
(A) Determining the scope and content of the prior art;
(B) Ascertaining the differences between the claimed invention and the prior art; and
(C) Resolving the level of ordinary skill in the pertinent art.
Objective evidence relevant to the issue of obviousness must be evaluated by Office personnel. Id. at 17-18, 148 USPQ at 467. The evidence may be included in the specification as filed, accompany the application on filing, or be provided in a timely manner at some other point during the prosecution. The weight to be given any objective evidence is determined on a case-by-case basis. The mere fact that an applicant has presented evidence does not mean that the evidence is dispositive of the issue of obviousness.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation (TSM) in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
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.
Rejections under 35 USC § 103
Claims 1 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Mills et al. (US-20220047596-A1) in view of the combined teaching of Reiss et al. (J Clin Oncol 39, 2497-2505(2021)) and Piha-Paul et al. (Clin Cancer Res (2019) 25 (21): 6309–6319).
Brief Discussion of Cited References
Mills et al.
Mills et al. (US-20220047596-A1) teach methods for treating cancer comprising administering a poly-ADP-ribose polymerase (PARP) inhibitor in combination with a bromodomain-containing protein 4 (BRD4) inhibitor. See abstract. Moreover, Mills et al. teach that BRD4, a member of the bromo-domain and extraterminal (BET) protein family, can be selectively targeted with small-molecule inhibitors. See Paragraph [0005]. Mills et al. teach that tumor cells lacking functional BRCA1, BRCA2, or other key components of the homologous recombination (HR) pathway, are highly sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitor; but that, although high response rates are achieved with PARP inhibitors, most tumors rapidly become resistant, including BRCA1/2 mutant cancers. See Paragraph [0006].
Mills et al. teach that the combined administration of the PARP inhibitor and BET inhibitor results in greater reduction in tumor growth or greater reduction in tumor mass relative to administration of PARP inhibitor or BET inhibitor alone. See Paragraph [0007]. Mills et al. teach that the administration of a PARP inhibitor in combination with the BET inhibitor prevents emergence of PARP inhibitor resistance. See Paragraph [0008]. Mills et al. teach that, in some aspects, the cancer to be treated using PARP inhibitor in combination with the BET inhibitor is breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, lung cancer, or melanoma. See Paragraph [0009].
Mills et al. teach that, in some aspects, the PARP inhibitor is Olaparib, BMN673, Niraparib, Rucaparib, or ABT888 (Veliparab). See Paragraph [0017]. Mills et al. teach that, in some aspects, the BET inhibitor is JQ1, GSK1210151A (I-BET151), GSK1324726A (I-BET-726), or AZD5153. See Paragraph [0017].
Mills et al. teach that, in some aspects, the BET inhibitor is administered at a dose of 10-40 mg/day, and the PARP inhibitor is administered at a dose of 200-400 mg/day. That is, Mills et al. teach dosing a BET inhibitor and a PARP inhibitor in a ratio from 1:40 to 1:5. See Paragraph [0011].
Reiss et al.
Reiss et al. (J Clin Oncol. 2021 Aug 1;39(22):2497-2505) teach an investigator-initiated, single-arm phase II study to assess the role of the PARP inhibitor rucaparib in the treatment of platinum-sensitive advanced pancreatic cancer. Table I recites that at least four of the platinum-sensitive cancer patients had received cisplatin. Treated patients received rucaparib 600 mg orally twice a day.
Piha-Paul et al.
Piha-Paul et al. (Clin Cancer Res (2019) 25 (21): 6309–6319) teach a first-in-human study of the pan-BET inhibitor mivebresib (ABBV-075) in patients having advanced solid tumors. Patients suffering from pancreatic cancer were among the patient population of the trial. See Table 1. Piha-Paul et al. teach that emerging data from in vitro studies indicate that BET inhibitors, such as mivebresib, may have improved activity when used in combination therapy. In particular, Piha-Paul et al. teach that “Several recent studies have also provided strong preclinical rationale for the combination of a BET inhibitor and PARP inhibitor in solid tumors.” See page 6318, first column.
Comparison Between the Claimed Invention and the Prior Art
Regarding claims 1 and 7-9, Mills et al. teach a method of treating a pancreatic cancer in a subject, the method comprising administering to the human subject an effective amount of a BET inhibitor and an effective amount of a PARP inhibitor, wherein the PARP inhibitor is rucaparib. Reiss et al. teach the PARP inhibitor rucaparib is used in the treatment of human pancreatic cancer patients who are platinum-sensitive, including those sensitive to cisplatin. Piha-Paul et al. teach mivebresib (ABBV-075) as a BET inhibitor in treating human pancreatic cancer patients.
Regarding claim 6. Mills et al. teach a method of claim 1, wherein the BET inhibitor and the PARP inhibitor are administered to the subject in a ratio from 1:40 to 1:5.
Differences Between the Claimed Invention and the Prior Art
Mills et al. do not list mivebresib (ABBV-075) among the BET inhibitors to be used in combination with a PARP inhibitor. Mills et al. do not expressly limit their methods to a pancreatic cancer patient who is responsive to a platinum-based therapy.
Reiss et al. focusses on treatment of platinum-sensitive advanced pancreatic cancer using PARP inhibitor rucaparib.
Piha-Paul et al. focusses on the treatment of advanced solid tumors using the BET inhibitor mivebresib (ABBV-075).
Conclusion of Obviousness
At the time of filing, it would have been obvious to practice the methods encompassed by claims 1 and 6-9. A finite number of PARP inhibitors and BET inhibitors were known for the treatment of pancreatic cancer. Mills et al. teach methods for treating cancer, including pancreatic cancer, comprising administering a BET inhibitor in combination with a PARP inhibitor, and teach that combined administration of the PARP inhibitor and BET inhibitor results in greater reduction in tumor growth or greater reduction in tumor mass relative to administration of PARP inhibitor or BET inhibitor alone. See Mills et al. at Paragraph [0007]. Mills et al. teach several PARP inhibitors, including rucaparib as recited in claim 1. See Mills et al. at Paragraph [0017]. As exemplified by Reiss et al., administering the PARP inhibitor rucaparib to patient sensitive to cisplatin was well known. See Reiss et al. at Table 1. While Mills et al. doesn’t specifically recite mivebresib (ABBV-075) as a BET inhibitor, Mills et al. does teach several other exemplary BET inhibitors. See Mills et al. at Paragraph [0017]. Piha-Paul et al. teach mivebresib as a BET inhibitor and that “Several recent studies have also provided strong preclinical rationale for the combination of a BET inhibitor and PARP inhibitor in solid tumors” thereby underscoring that those of ordinary skill the art would appreciated that mivebresib was among those BET inhibitors suitable for administration in combination with a PARP inhibitor. See Piha-Paul et al. at page 6318, first column.
Here, given the finite number of PARP inhibitors and BET inhibitors, it would have been obvious to choose from the finite number of identified, predictable solutions to arrive at the claimed invention. The motivation to do so would have been to create an alternative treatment for pancreatic cancer. The teachings of Mills et al. provide a reasonable expectation of success.
Regarding the recitation of claim 6 that the BET inhibitor and the PARP inhibitor are administered to the subject at a weight ratio of 1:10, Mills et al. teach that the BET inhibitor and the PARP inhibitor are administered to the subject in a ratio from 1:40 to 1:5, and Reiss et al. teach dosing rucaparib at 600 mg orally twice a day. A prima facie case of obviousness is created when the claimed ranges or values overlap, lie inside, or are merely close to those disclosed in the prior art. See MPEP § 2144.05. Moreover, “[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). See MPEP § 2144.05. See also Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results). Here, given the ratios taught by Mills et al. and the rucaparib dose taught by Reiss et al., finding the optimal dose for the combined therapy would have required no more than routine experimentation.
For the reasons provided, the methods encompassed by claims 1 and 6-9 were obvious at the time of filing.
Conclusion
No claim is currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRADLEY S MAYHEW whose telephone number is
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/BSM/Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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