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 .
Information Disclosure Statement
The information disclosure statement (IDS) dated 03/25/2026 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 03/25/2026 are acknowledged.
The examiner noticed a typographical errors in the listed claim numbers in nonstatutory double patenting rejections. Specifically, in the statue of the nonstatutory double patenting rejections, claims 65-67 and 71-74 are not listed. However, the rejections correctly pointed to these limitations in the teachings of Behenna et al. The reason or confusion for this typographical error may be because these claims were marked as withdrawn [see claims filed on 03/28/2024 and 08/02/2023] and the examiner examined all claims to avoid delay in the prosecution. Applicants cooperation in this regard is highly appreciated. Typographical error is regretted.
The nonstatutory double patenting rejection over copending application number 17/816,271 (now US 12,312,331) is withdrawn, in light of cancelation corresponding method claims.
With regard to pending other rejections, applicants’ arguments for the 103 and nonstatutory double patenting rejections are found not persuasive. Accordingly, the previous rejections are maintained and modified to address claim amendments and typographical errors.
Response to Arguments
Applicants’ argue that the Office Action at page 4 admits that "none of the art teach combination of both, but identified them separately in cancerous cells" and that "art focuses on individual genes, but not combination of genes." (emphasis added). The Office Action at 4 further states that "expression of p16 is expected in the disclosure of Behenna, absent evidence to the contrary." This conclusory statement with insufficient rationale is factually incorrect. As previously articulated in the Appeal Brief, expression of p16 is not expected in all cancers. On the contrary, p16 is absent in many cancers. See Dong at page 62, left column, first paragraph, teaching that 65% of benign tumors lacked immunodetectable p16 protein and 11% of malignant tumors lacked immunodetectable p16. See also Ligget at Table 1, which describes the inactivation of p16 in various cancers, including breast (40%), ovarian (25%), non-small-cell lung cancer (35%), and small-cell lung cancer (5%). Thus, there is no expectation of expression of p16 in the disclosure of Behenna.
Claim simply require presence of p16 and so, claimed method is applicable only if p16 is detected. It does not matter how much percentage of p16 is present in the tumor cells.
Cited art is already established the facts that tumors, such as ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer etc., wherein the cancer is characterized by expression of CCNE1 and p16, and both are associated with CDK2. As explained in the rejection, none of the art teach combination of both, but identified them separately in cancerous cells. Probably art focuses on individual genes, but not combination of genes. There may be some other genes expressed at the same time and associated with CDK2 diseases. So, expression of p16 is expected in the disclosure of Behenna. Moreover, Behenna teaches CDK2 associated diseases, and did not mention about CDK4/6 targeting therapies.
With regard to nonstatutory double patenting rejections, specifically applicants arguments on patent term filing dates…..
MPEP § 804(I)(B)(1)(a) states that the patent term filing date of an original utility or plant application filed on or after June 8, 1995 is the earliest of: (1) The actual filing date of the application; or (2) The filing date of the earliest application for which the application claims the benefit of an earlier filing date under 35 U.S.C. 120, 121, 365(c), or 386(c). See 37 CFR 1.78 … Benefit claims under 35 U.S.C. 119(e) [i.e., provisional applications] and foreign priority claims under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) or (b) are not taken into account when determining the term of an issued patent (see 35 U.S.C. 154(a)(2) and (a)(3) ), and therefore, are not taken into account in determining the patent term filing date of an application.”). See also 35 U.S.C. 154(a)(2) (“TERM. – Subject to the payment of fees under this title, such grant shall be for a term beginning on the date on which the patent issues and ending 20 years from the date on which the application for the patent was filed in the United States or, if the application contains a specific reference to an earlier filed application or applications under section 120, 121, or 365(c) of this title, from the date on which the earliest such application was filed.”). Note again that 119(a)-(e) is not being relied upon for this 20 year term.
Please note that there are two justifications for NSDP. See In re Hubbell, 709 F. 3d 1140 (Fed. Cir. 2013) (“There are two justifications for obviousness-type double patenting. The first is ‘to prevent unjustified timewise extension of the right to exclude granted by a patent no matter how the extension is brought about.’ … The second rationale is to prevent multiple infringement suits by different assignees asserting essentially the same patented invention … this court reaffirmed the multiple assignee harassment rationale and applied it to a situation where, as here, the patents were related to the application only by way of a common inventor … as we recognized in Fallaux, the harassment justification is ‘particularly pertinent’ in cases where, as here, the application and the conflicting patent are not commonly owned."). See also In re Fallaux, 564 F.3d 1313, 1318–19 (Fed. Cir. 2009) (“[T]here is a second justification for obviousness-type double patenting--harassment by multiple assignees.”). See also MPEP § 804(II)(B)(“A rejection based on nonstatutory double patenting is based on a judicially created doctrine grounded in public policy so as to [1] prevent the unjustified or improper timewise extension of the right to exclude granted by a patent … [2] A double patenting rejection also serves public policy interests by preventing the possibility of multiple suits against an accused infringer by different assignees of patents claiming patentably indistinct variations of the same invention. In re Van Ornum, 686 F.2d 937, 944-48, 214 USPQ 761, 767-70 (CCPA 1982).”). As an example, see Appeal 2018-001186 (11/566,721) (“Appellant does not dispute the Examiner’s finding that the claims are, in fact, obvious over one another, but rather contends that because the instant application and US 8,759,311 share a common expiration date, there would be no improper extension. However, ‘there is a second justification for obviousness-type double patenting--harassment by multiple assignees.’ In re Fallaux, 564 F.3d 1313, 1318–19 (Fed. Cir. 2009) … We note that the assignee of US 8,758,311 is Nemaura Pharma Limited and the assignee of the instant application is the inventor, Dewan Fazlul Hoque Chowdhury. Therefore, the, harassment justification for obviousness-type double patenting is particularly pertinent here because the . . . application and the . . . patent[] are not commonly owned … We therefore affirm the obviousness-type double patenting rejection.”).
Accordingly, it doesn’t matter whether there will be an unjustified extension of patent term or not (i.e., you do not need to calculate this). There would still be potential infringement by multiple owners (i.e., justification for the rejection regardless of whether there was an unjustified extension of patent rights). Accordingly, the rejection(s) are still applicable. The patent terms can be extended, etc. (e.g., PTA, PTE, etc.) and thus it is not so straightforward to even calculate this. Further, examiners generally need not make such calculations. See Appeal 2020-002836 (14/081,917) (“Appellant does not direct us to a requirement in the MPEP or elsewhere for an examiner to make a patent term assessment before issuing an obviousness-type double-patenting rejection and we are not aware of any such requirement”).
Claim Rejections - 35 USC § 103 [Maintained and modified]
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 5-10,13-21, 65-69, 71-74 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Behenna et al (US 2018/0044344 A1) in view of Dong et al (Int.J.Cancer, 74, 57-63, 1997), Serrano et al (Nature, vol.366, 16 Dec 1993, 704-707), Liggett et al (Journal of Clinical Oncology, vol.16, No.3, 1998, 1197-1206; see applicants filed IDS dated 11/29/2021), Romagosa et al (Oncogene, 2011, 30, 2087-2097; see applicants filed IDS dated 08/02/2023) and Yang et al (Oncotarget, 6, 25, 20801-12, 2015).
For claims 5-6 and 76:
Behenna et al teach a method for the treatment of a cancer mediated by CDK2 in a subject, comprising administering to the subject a CDK2 inhibitor, or a pharmaceutically acceptable salt thereof, in an amount that is effective for treating cancer, wherein cancer is selected from the group consisting of ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer etc., wherein the cancer is characterized by amplification or overexpression of CCNE1 and/or CCNE2, wherein the CDK2 inhibitor is selected from the following generic formula:
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, see the definitions of variables in page 2. Behenna et al further disclose various species for their generic compound, which are structurally similar or identical. For example, compound “8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one” (see Ex.No. 190 (A) in Table 1), which is identical to applicants listed compound 7. [See corresponding text in claims 20-21 and 1-18; 0042; 0737-0756; 0818 and Table 1].
The difference is that Behenna et al is silent on applicants limitation of “expression of p16 protein”. This difference can be cured by the following art, see below.
Dong et al teach increased expression of CDKN2A or p16 in ovarian cancer associated with progression and unfavorable prognosis [see abstract].
Further, Dong et al [see abstract] teach the following:
Most benign tumors showed no p16 expression in the tumor cells, whereas only 11% of malignant cancers were p16 negative. A high proportion of p16-positive tumor cells was associated with advanced stage and grade, and with poor prognosis in cancer patients.
For FIGO stage I tumors, a high proportion of p16-positive tumor cells was associated with poorer survival, suggesting that accumulation of p16 is an early event of ovarian tumorigenesis.
In contrast to tumor cells, high expression of p16 in the surrounding stromal cells was not associated with the stage and grade, but was associated with longer survival.
When all parameters were combined in a multivariate analysis, high p16 expression in stromal cells was not an independent predictor for survival, indicating that low p16 expression in stromal cells is associated with other markers of tumor progression. High expression of p16 in the stromal cells of tumors from long-term survivors suggests that tumor growth is limited to some extent by factors associated with p16 expression in the matrix.
High expression of p16 in tumor cells was found to be associated with progression and poor prognosis of ovarian cancer, whereas, conversely, high expression in stromal cells was a predictor of longer survival.
Serrano et al teach the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes, and resulting in inhibition of cell proliferation [see abstract and last paragraph of article in page 707].
Liggett et al teach p16 as a tumor suppressor gene in cancer [see abstract; 3rd paragraph of right column in page 1202].
Romagosa et al also teach p16 as a tumor suppressor and a marker in treating cancers [see whole document and preferably sections “p16Ink4a as a prognostic maker” and “p16Ink4a and treatment” in pages 2092-2093].
So, based on the above advantages, p16 can be a marker or can be a tumor suppressor. Therefore, a skilled person in the art would be motivated to take advantage of its properties and would include it in the treatment of cancers. For example, if a patient is positive to p16, then skilled person can know the status of cancer, viz, benign or malignant and stage of cancer etc, and since it binds to CDK4 or inhibits CDK4, then it can have additional advantages in combination with CDK2 inhibitors in treating the cancers.
For claim 7:
Behenna et al teach overexpression of CCNE1 in cancers [see 0042], and this can be interpreted as expression must be at least 1.5 times more than the control expression level.
For claim 8:
p16 gene and its protein sequence is already known. For example, see listed sequence in page 705 in the teachings of Serrano et al.
For claims 9-10:
Behenna et al further teach that CDK2 inhibitor of the invention may be administered in combination with one or more: targeted agents, such as inhibitors of PI3 kinase, mTOR, PARP, IDO, TDO, ALK, ROS, MEK, VEGF, FLT3, AXL, ROR2, EGFR, FGFR, Src/Abl, RTK/Ras, Myc, Raf, PDGF, AKT, c-Kit, erbB, CDK4/CDK6, CDK5, CDK7, CDK9, SMO, CXCR4, HER2, GLS1, EZH2 or Hsp90, or immunomodulatory agents, such as PD-1 or PD-L1 antagonists, OX40 agonists or 4-1BB agonists etc [see 0887-0888].
For claims 13-15:
Behenna et al do not teach applicants claimed limitation of gene copy number explicitly. This can be expected in the teachings of Behenna et al or can be cured by Yang et al.
Yang et al teach that the relative CCNE1 gene copy numbers in ovarian cancer cells and the relative copy number of CCNE1 gene is 6 in OVCAR8, OVCAR3 (Fig. 1c). Further teach that the comparison of control expression of CCNE1 to the ovarian tumor samples (Fig. 1) and measurement of CCNE1 mRNA and protein in a panel of established ovarian cancer lines (Fig. 1A, 1B).
So, from the teachings of Yang et al it is obvious that the amplification of the CCNE1 gene comprises gene copy numbers more compared to the control. Further teach that the CCNE1 gene is amplified in ovarian cancers, can be used as a biomarker to treat ovarian cancer in patients and further gene copy numbers amplified in various cancer cells, e.g. OVCAR3, OVACAR5, OVCAR8, OCC1, OVCAR429 etc. (Fig. 1c). The number of copies in different ovarian cancer cells range from 1-6 as demonstrated in Fig. 1c.
Therefore, it is obvious to a person of ordinary skill in the art that gene copy numbers of amplified CCNE1 depends on the type of ovarian cancer cell(s) and type(s) and can be at least 3 or 5 or 21 as claimed. A person of ordinary skill in the art would have been motivated to measure the amplification/gene copy numbers for diagnosis and to provide targeted therapy in ovarian cancer individuals.
For claims 16-17:
These limitations would have been obvious over Yong et al because control expression level is a pre-established cut off value. Further it is obvious that expression level of a gene in cancer or tumors are measured against control expression values. Also a person of ordinary skill in the art would have found it obvious to measure against a control expression level of a sample obtained from a subject that has not responded to the treatment with a CDK2 inhibitor to find whether this subject responds to the treatment and also for analysis to investigate the treatment based on different ovarian cancer type(s) and subject population. Not sure the purpose of these limitations.
For claims 18-21:
In fact, one of ordinary skill in the art would have found it obvious to measure mRNA and protein expression levels of CCNE1 in ovarian cancer cells as taught by Yong et al to analyze which cancer cells exhibit more or less CCNE1 expression and target the ovarian cancer therapy based on the results. Yong’s teaching of RT-PCR and immunoblotting techniques to measure the expression of CCNE1 (Fig. 1). These limitations trivial, can be found in standard text books, and not sure why applicants are included these limitations in the claims. Any specific purpose?
For claim 68:
Behenna et al teach compound “8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one” is identical to applicants listed compound [see 0738].
For claims 65-67, 69 and 71-74:
Behenna et al teach that in their method of treating cancer, wherein cancer is selected from the group consisting of breast cancer, ovarian cancer, uterine cancer, lung cancer, stomach cancer etc. [see 0818].
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, direct link between recited cancers and applicants recited marker genes or peptides, CDK2 inhibitors for treating cancers and advantages of p16 etc., were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
In this case, applicants cited CCNE1 and p16 are known markers for various cancers, such as ovarian or breast cancer etc., and it would be logical to use these markers, separately or in combination, as a basis for screening and then treating CDK2 associated cancers. See also U.S. Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007) ("When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under§ 103. Here, the known CCNE1 and p16 ovarian cancer markers constitute a finite number of identified, predictable solutions (i.e., present or absent in ovarian cancer etc.) and thus a person of skill would be motivated to try them individually or in combination. See also Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (species claim held obvious where it recited one of 1200 possible combinations of embodiments disclosed by reference and where reference suggested no preference for claimed embodiment); see also id. at 808 (That a reference “discloses a multitude of effective combinations does not render any particular formulation less obvious.”).
In addition, p16 can be a marker or can be a tumor suppressor. Therefore, a skilled person in the art would be motivated to take advantage of its properties and would include it in the treatment of cancers. For example, patient is positive to p16, then skilled person can know the status of cancer, viz, benign or malignant and stage of cancer etc, and since it binds to CDK4 or inhibits CDK4, then it can have additional advantages in combination with CDK2 inhibitors in treating the cancers.
The motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited references and to make the instantly claimed method with a reasonable expectation of success.
Nonstatutory Double Patenting Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
I. Claims 5-10, 13-21, 65-69, 71-74 and 76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 38-40 of US 11,447,494 B2 in view of Behenna et al (US 2018/0044344 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Claims of instant application are drawn to A method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering a CDK2 inhibitor, wherein the human subject has been previously determined to:
(i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; and/or (c) express a p16 protein; and
(ii) (a) have an amplification of the cyclin El (CCNE1) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1;
wherein the disease or disorder associated with CDK2 is selected from the group consisting of ovarian cancer, stomach cancer, endometrial cancer, and lung cancer; and wherein the CDK2 inhibitor is selected from the listed CDK2 inhibitors.
Claims 38-40 of US patent are drawn to a method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering to the human subject the compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the human subject has been previously determined to: (i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; (ii) (a) have an amplification of the cyclin E1 (CCNE1) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1. Since the compounds of claim 1 is administered to treated CDK2 associated diseases, and so, these compounds are interpreted as CDK2 inhibitors. Alternatively, according to specification these compounds are CDK2 inhibitors.
The only difference is that the claims of US patent is silent of applicants recited specific CDK2 inhibitors and recited cancers.
This can be cured by the following art:
Behenna et al teaches CDK2 inhibitor, viz., “8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one” (see Ex.No. 190 (A) in Table 1), which is identical to applicants listed compound 7 in the claim 1. Behenna et al, further teaches that their compound is useful to treat various CDK2 associated diseases, viz., ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer etc. If compound shows CDK2 inhibition and used for treating CDK2 associated diseases, then that compound is exchangeable or equivalent.
Further, MPEP 2144.06 states the following:
II. SUBSTITUTING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.).
So, the motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
II. Claims 5-10, 13-21, 65-69, 71-74 and 76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-36 of US 11,440,914 B2 in view of Behenna et al (US 2018/0044344 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Claims of instant application are drawn to A method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering a CDK2 inhibitor, wherein the human subject has been previously determined to:
(i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; and/or (c) express a p16 protein; and
(ii) (a) have an amplification of the cyclin El (CCNE1) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1;
wherein the disease or disorder associated with CDK2 is selected from the group consisting of ovarian cancer, stomach cancer, endometrial cancer, and lung cancer; and wherein the CDK2 inhibitor is selected from the listed CDK2 inhibitors.
Claim 32 of US patent are drawn to a method of treating a cancer associated with CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of claim 1, or pharmaceutically acceptable salt thereof, wherein the cancer is selected from the group consisting of ovarian, endometrial, esophagus, adenocarcinoma, adenocarcinoma of the esophagus, urothelial, gynecological, ovarian serous cystadenocarcinoma, uterine carcinoma, cervical carcinoma, endocervical adenocarcinoma, stomach (gastric), esophageal, breast, triple negative breast cancer, lung, non-small cell lung cancer, lung squamous cell carcinoma, bile duct, and bone. The dependent claims 33-37 further limit claim 32 to the method of claim 32, wherein the human subject has been previously determined to: (i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; (ii) (a) have an amplification of the cyclin E1 (CCNE1) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1. Since the compounds of claim 1 is administered to treated CDK2 associated diseases, and so, these compounds are interpreted as CDK2 inhibitors. Alternatively, according to specification these compounds are CDK2 inhibitors.
The only difference is that the claims of US patent is silent of applicants recited specific CDK2 inhibitors and cancers.
This can be cured by the following art:
Behenna et al teaches CDK2 inhibitor, viz., “8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one” (see Ex.No. 190 (A) in Table 1), which is identical to applicants listed compound 7 in the claim 1. Behenna et al, further teaches that their compound is useful to treat various CDK2 associated diseases, viz., ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer etc. If compound shows CDK2 inhibition and used for treating CDK2 associated diseases, then that compound is exchangeable or equivalent.
Further, MPEP 2144.06 states the following:
II. SUBSTITUTING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.).
So, the motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
III. Claims 5-10, 13-21, 65-69, 71-74 and 76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-33 and 35 of US 11,919,904 B2 in view of Behenna et al (US 2018/0044344 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Claims of instant application are drawn to A method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering a CDK2 inhibitor, wherein the human subject has been previously determined to:
(i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; and/or (c) express a p16 protein; and
(ii) (a) have an amplification of the cyclin El (CCNE1) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1;
wherein the disease or disorder associated with CDK2 is selected from the group consisting of breast cancer, ovarian cancer, stomach cancer, endometrial cancer, and lung cancer; and wherein the CDK2 inhibitor is selected from the listed CDK2 inhibitors.
Claims 1, 27-31 and 33-34 of copending application, in light of “comprising” language, can be summarized to a method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering to the human subject a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the human subject has been previously determined to:(i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; (ii) (a) have an amplification of the cyclin El (CCNEl) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1. Since the compounds of claim 1 is administered to treated CDK2 associated diseases, and so, these compounds are interpreted as CDK2 inhibitors. Alternatively, according to specification these compounds are CDK2 inhibitors.
The only difference is that the claims of US copending application is silent of applicants recited specific CDK2 inhibitors.
This can be cured by the following art:
Behenna et al teaches CDK2 inhibitor, viz., “8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one” (see Ex.No. 190 (A) in Table 1), which is identical to applicants listed compound 7 in the claim 1. Behenna et al, further teaches that their compound is useful to treat various CDK2 associated diseases, viz., ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer etc. If compound shows CDK2 inhibition and used for treating CDK2 associated diseases, then that compound is exchangeable or equivalent.
Further, MPEP 2144.06 states the following:
II. SUBSTITUTING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.).
So, the motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
IV. Claims 5-10, 13-21, 65-69, 71-74 and 76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46-50 and 52 and 74 of US copending application number 18/179,838 in view of Behenna et al (US 2018/0044344 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Claims of instant application are drawn to A method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering a CDK2 inhibitor, wherein the human subject has been previously determined to:
(i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; and/or (c) express a p16 protein; and
(ii) (a) have an amplification of the cyclin El (CCNE1) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1;
wherein the disease or disorder associated with CDK2 is selected from the group consisting of ovarian cancer, stomach cancer, endometrial cancer, and lung cancer; and wherein the CDK2 inhibitor is selected from the listed CDK2 inhibitors.
Claims 46-50 and 52 of copending application, in light of “comprising” language, can be summarized to a method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering to the human subject a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the human subject has been previously determined to:(i) (a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or (b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions; (ii) (a) have an amplification of the cyclin El (CCNEl) gene; and/or (b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1. Since the compounds of claim 1 is administered to treated CDK2 associated diseases, and so, these compounds are interpreted as CDK2 inhibitors. Alternatively, according to specification these compounds are CDK2 inhibitors.
The only difference is that the claims of US copending application is silent of applicants recited specific CDK2 inhibitors.
This can be cured by the following art:
Behenna et al teaches CDK2 inhibitor, viz., “8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one” (see Ex.No. 190 (A) in Table 1), which is identical to applicants listed compound 7 in the claim 1. Behenna et al, further teaches that their compound is useful to treat various CDK2 associated diseases, viz., ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer etc. If compound shows CDK2 inhibition and used for treating CDK2 associated diseases, then that compound is exchangeable or equivalent.
Further, MPEP 2144.06 states the following:
II. SUBSTITUTING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.).
So, the motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/ Primary Examiner, Art Unit 1658
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