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, 3-4, 9-11, 13, 15, 17, 19, 22, 25, 27, 34, 36, 38, 43-44 and 46 are pending in the present application file.
Election/Restrictions
Applicant’s election of Group I (claims 1, 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34; directed to a method of treating cancer) and a species of onvansertib and olaparib without traverse in the reply filed April 29, 2026 is acknowledged.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species is not allowable over the prior art as indicated in the rejection under 35 U.S.C 103.
As the Applicant' s elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1, 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34 have been examined to the extent that they embrace and are readable on the elected embodiment and the above identified nonelected species. Claims 1, 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34 have been found to be not allowable over the prior art.
Claims 36, 38, 43-44 and 46 are withdrawn from consideration by the Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Priority
The following continuity data is acknowledged in the present application file:
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Information Disclosure Statement
The Information Disclosure Statement(s) filed October 23, 2023 have been acknowledged by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Claim Interpretation
The limitation “thereby inhibiting progression of the cancer”, recited at the end of present claim 1, is intended as an intended outcome of the method of treating cancer of claim 1.
Regarding an intended use limitation, MPEP 2111.02(II) notes:
“If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”.
Claims which limit or further define the intended outcome of treating cancer do not impart further limitation on the active steps of the method of present claim 1 or the subjects to which the method is to be applied. The active steps of the recited method comprise administration of a Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor to a subject with cancer. If the prior art structure is capable of performing the intended use, then is meets the claim.
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, 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34 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 a method of treating breast, ovarian, pancreatic, and prostate cancer comprising administrating a Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor, does not reasonably provide enablement for treatment or prevention of every other cancer or the prevention of breast, ovarian, pancreatic, and prostate cancer by administration of said combination. 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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
the nature of the invention,
the state of the prior art,
the predictability or lack thereof in the art,
the amount of direction or guidance present,
the presence or absence of working examples,
the breadth of the claims,
the quantity of experimentation needed, and
the level of the skill in the art.
In the instant case,
The nature of the invention
The nature of invention of claim 1 is the treatment of cancer with Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor. Paragraphs 49-50 of the specification provides that the term “treating” includes prophylactic and therapeutic purposes. Furthermore, the specification discloses where the methods can be used for the treatment of various types of cancer, including ‘other neoplastic malignancies’, for which no enablement is provided. See pgs. 11-13.
The state of the prior art and The predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat or prevent which specific diseases and by what mechanism).
There is no absolute predictability even in view of the seemingly high level of skill in the art.
The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below:
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
Applicants are claiming the treatment and prevention of various cancers.
The state of the prior art is that cancer therapy and prevention remain highly unpredictable. The various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment and prophylaxis protocol. It is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, that cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (see Golub et al. page 531).
Furthermore, it is known that chemotherapy is most effective against tumors with rapidly dividing cells and that cells of solid tumors divide relatively slowly and chemotherapy is often less effective against them. Additionally, it is known that 75-80% of cancer types (in the US) are due to environmental factors and, in theory, cannot be prevented (Rothman et. al., see page C2, col. 1, Lines 8-23).
Hence, in the absence of a showing of correlation between all the diseases claimed as capable of treatment and prevention by the administration of the compounds of the claims, one of skill in the art is unable to fully predict possible results from the administration of the compound of the claims due to the unpredictability. It is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, that cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy.
The amount of direction or guidance present and The presence or absence of working examples
The only direction or guidance present in the instant specification is the listing of diseases applicant considers as treatable on pages 11. Additionally, in vitro data for the treatment of breast, ovarian, pancreatic, and prostate cancer via the claimed composition is found on pages 39-50.
Data, in vitro or in vivo, for the prevention of breast, ovarian, pancreatic, and prostate cancer, or any other cancer, is lacking from the disclosure.
Moreover, the disclosure does not provide how the in vitro data correlates to the treatment and prevention of the assorted cancers claimed. The uses covered by the claims are not enabled based solely on the assay testing reported in the specification. Various studies are required to enable compounds in clinical development; for example, development routinely relies on animal models in addition to iterative assays, not assay testing as done herein. Note Hoffman V. Klaus 9 USPQ2d 1657 (1988) regarding the standard of testing that is necessary to establish the likelihood of in vivo use. Also see Ex parte Powers 220 USPQ 924 (1982) regarding the absence of animal studies and the absence of correlation between the studies conducted in vitro and the diseases to be treated. In the absence sufficient testing of animal models, assays for treating cancer outside of breast, ovarian, pancreatic, and prostate cancer or prevention of any cancer, the claims are not enabled for a skilled artisan.
Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The breadth of the claims
The breadth of the claims is the treatment of cancer with Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor. Page 10 of the specification provides that the term “treating” includes curing and prevention. Furthermore, the instant claims cover ‘cancer’, which is taken to encompass all forms of cancer, for which there is no enablement provided.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what cancers out of the multitude claimed would be benefited by the administration of the combination of compounds of the claims.
The level of the skill in the art
The level of skill in the art is high, that of an MD or PHD capable of performing and analyzing a high throughput screen.
However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the compound of the instant claims for the treatment and prevention of the various claimed cancers as a result, necessitating one of skill to perform an exhaustive search for which cancers can be treated or prevented by what compounds of the instant claims in order to practice the claimed invention.
Factors such as “sufficient working examples”, “the level of skill in the art” and “predictability”, etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. {In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which hyper-proliferative can be treated or prevented by the composition encompassed in the instant claim, with no assurance of success.
Claims 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34, which are dependent on claim 1, are similarly rejected.
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 11, 25 and 27 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.
Claims 11 and 27 recite limitations which are defined by an intended outcome.
When claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008). See MPEP 2173.05(g). Without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. See Ariad Pharmaceuticals., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353, 94 USPQ2d 1161, 1173 (Fed. Cir. 2010) (en banc).
In this situation, it is indefinite which PARP inhibitor, PLK1 inhibitor, or combination of PARP inhibitors or PLK1 inhibitors, are required to meet the limitation of the claims.
Claim 25 recites “TKM-080301” is which is indefinite as TKM-080301 described in the present specification (see paras 8, 19, 83, 130); however no structure is provided, and the explicit structure of TKM-080301 has not been disclosed the prior art. It would be unclear to one of ordinary skill in the art what PLK1 inhibitor or structure of PLK1 inhibitor is recited/required by the present claim.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11 and 27 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Present claim 1 recites a method of treating cancer, the method comprising: administrating a Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor to a subject with cancer. The limitations of present claims 11 and 27, which are dependent upon claim 1, are not considered further limiting as it presumed that any combination of a Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor which meets the requirements of claim 1, treating cancer, will also have the required properties to meet the limitations of claims 11 and 27.
This method recites active step of administering a combination of a Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor but does not include additional active steps for achieving the claimed results/limitations of claims 11 and 27. As such it is presumed the results/limitations presented in claims 11 and 27, can be any combination of a Poly-(ADP-ribose) polymerase (PARP) inhibitor and a Polo-like kinase 1 (PLK1) inhibitor of claim 1 as no additional agent or process steps are claimed.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1, 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li, Jie, et al. "Targeting Plk1 to enhance efficacy of olaparib in castration-resistant prostate cancer." Molecular cancer therapeutics 16.3 (2017): 469-479.), in view of García (García, Iris Alejandra, et al. "Therapeutic opportunities for PLK1 inhibitors: Spotlight on BRCA1-deficiency and triple negative breast cancers." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 821 (2020): 111693.) and Patterson (Jesse Christopher Patterson et al. Combination of selective polo-like kinase 1 (PLK1) inhibitor PCM-075 with abiraterone in prostate cancer and non-androgen-driven cancer models.. J Clin Oncol 36, 369-369(2018).).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Li discloses a method of treating cancer comprising administration of a Poly-(ADP-ribose) polymerase (PARP) inhibitor (Olaparib) and a Polo-like kinase 1 (PLK1) inhibitor (BI2536), where the addition of PLK1 inhibitor led to a robust sensitization of olaparib in 22RV1, a BRCA1-deficient CRPC cell line, as well as in CRPC xenograft tumors (see abstract as well as present claims 1, 4, 13, 22 and 25). Li discloses PARP inhibitors (PARPi) are strikingly toxic to cells with defects in HR (see pg 469, r.c., para 1; see present claim 3). Li discloses where both olaparib and BI2536 were administered twice weekly (see pg 471, l.c., para 2 and present claims 15 and 17). Li provides where the PARPi-PLK1 inhibitor combination was administered in a cycle of 2 weeks, with BI2536 intravenously injected (12 mg/kg), olaparib (50 mg/kg) administered by oral gavage, or a combination of both drugs (see Fig. 2 and dosage of present claim 26).
Li discloses where PLK1 inhibition with BI2536 sensitized 22RV1 cells to PARPi Olaparib, with the combination acting synergistically to provide a potential new treatment for prostate cancer and CRPC patients (see abstract; pg. 471, r.c., paras. 2 and 4; pg. 478, l.c., para 1). Li also discloses where the combination of BI2536 and Olaparib acted synergistically in BRCA1 wild-type, p53-mutant MDA-MB-231 and C4-2 cells when p53 activity was inhibited (see pg 473, r.c., para 1).
Regarding claims 11 and 27, which require various outcomes associated with the administration of the combination of present claim 1, a recitation of the intended outcome of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art is capable of performing the intended use, if meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997). See MPEP 2112.02 (II).
Without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. See Ariad Pharmaceuticals., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353, 94 USPQ2d 1161, 1173 (Fed. Cir. 2010) (en banc).
Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Granting a patent on the discovery of an unknown but inherent function "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991). See MPEP 2145, Section II. "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
When the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). "While the references do not show a specific recognition of that result, its discovery by appellants is tantamount only to finding a property in the old composition." 363 F.2d at 934, 150 USPQ at 628 (emphasis in original)).
The present claims recite the administration of combination of a PARP inhibitor and a PLK1 inhibitor, which is disclosed in the prior art. The prior art also discloses the PARPi-PLK1 inhibitor composition within the method of treating cancer, which is identical to the present claims. A composition and its properties are inseparable and a composition of identical structure would be expected to possess identical properties, such as the ability to achieve complete response and one or more of the required alternatives of present claims 11 and 27.
Regarding claim 19 which is directed to daily administration of the PARP inhibitor, it would have been obvious to one of ordinary skill in the art to adjust the administration schedule for the PARP inhibitor, as well as the PLK1 inhibitor, to the subject having cancer during routine optimization. There would be a reasonable expectation of success based on the administration guidance provided by Li.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Li does not disclose where PLK1 inhibitor is onvansertib (see present claim 26).
Li does not disclose wherein the cancer in a homologous-recombinant deficient cancer (see present claim 3).
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Garcia discloses the following in the abstract regarding PLK1 inhibitor for treating cancer, including triple negative breast cancers (TNBCs) and BRCA1-deficient cancers, including prostate cancers:
[G]reat efforts are being invested to position PLK1i in the treatment of specific types of cancers with revised dosages schemes. In this mini review we focus on two potential niches for PLK1i that are supported by recent evidence: triple negative breast cancers (TNBCs) and BRCA1-deficient cancers. On the one hand, we recollect several lines of strong evidence indicating that TNBCs are among the cancers with highest PLK1 expression and sensitivity to PLK1i. These findings are encouraging because of the limited therapeutics options available for TNBC patients, which rely mainly on classic chemotherapy. On the other hand, we discuss recent evidence that unveils synthetic lethality induction by PLK1 inhibition in BRCA1-deficient cancers cells. This previously un foreseen therapeutic link between PLK1 and BRCA1 is promising because it defines novel therapeutic opportunities for PLK1i not only for breast cancer (i.e. TNBCs with BRCA1 deficiencies), but also for other types of cancers with BRCA1-deficiencies, such as pancreatic and prostate cancers.
Garcia further provides the following regarding efficacy of PLK1 inhibitors for the treatment of TNBC and BRCA1-deficient cancers in pg 5, Section 4:
In line with such hypothesis, an unbiased screening targeting the human kinome recently performed in our lab unveiled that PLK1 inhibitors trigger strong synthetic lethality in BRCA1-deficient cells in a dose-range where they depict little cytotoxic effect in BRCA1-proficient cells. In this study, we did not find acute genomic instability induction by the PLK inhibitor Volasertib within the synthetic lethal dose-range, thus suggesting that this type of treatment might induce a “clean” type of antitumoral response in BRCA1-deficient cells, attenuating genomic instability and delaying the acquisition of resistance mechanisms in cancer cells. Taken together with the evidence discussed in the previous section, these findings stimulate the design of future clinical trials focused on TNBC patients that consider BRCA1 status as a stratification marker.
Patterson discloses where the combination of PCM-075 (also known as onvansertib) with abiraterone was examined in metastatic castration-resistant prostate cancer (mCRPC) models and other cancer types for synergistic interaction (see Abstract; Background). Patterson provides where synergy was observed between abiraterone and PLK1i, including PCM-075, in models of CRPC, in C4-2 cells (see Abstract; Results).
Li discloses a method of treating cancer comprising administration of a Poly-(ADP-ribose) polymerase (PARP) inhibitor (Olaparib) and a Polo-like kinase 1 (PLK1) inhibitor (BI2536), where the addition of PLK1 inhibitor led to a robust sensitization of olaparib in 22RV1, a BRCA1-deficient CRPC cell line. Patterson discloses where the combination of PCM-075 (also known as onvansertib) with abiraterone displayed synergy in metastatic castration-resistant prostate cancer (mCRPC) models. Garcia discloses where PLK1 inhibitors, including Volasertib, trigger strong synthetic lethality in BRCA1-deficient cells which provide therapeutic opportunities for PLK1i not only for breast cancer (i.e. TNBCs with BRCA1 deficiencies), but also for other types of cancers with BRCA1-deficiencies, such as pancreatic and prostate cancers.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Li, Garcia and Patterson as they are all directed to methods of treating cancer, including either BRCA1-deficient cancers or prostate cancers (CRPC). One of ordinary skill would be motivated to substitute PLK1 inhibitors onvansertib for BI2536, in the method of treating CRPC with a combination of a PARPi, such as olaparib, based on the efficacy disclosed by Li and Patterson. Garcia provides further support for testing various PLK1 inhibitors in treating BRCA1-deficient prostate cancers. There would be a reasonable expectation towards the success of treating cancer based on the data provided in each of the prior art references.
The present claims are prima facie obvious and are properly rejected.
Conclusion
Claims 1, 3-4, 9-11, 13, 15, 17, 19, 22, 25-27 and 34 are rejected.
Claims 36, 38, 43-44 and 46 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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/QUINCY A. MCKOY/
Patent Examiner
Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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