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 .
Status of Claims
Claims 1, 4-8, 12, 16-17, 20, 22, 24-27, 29, 33-34, 36, 39, and 44 are pending in the instant application.
Claims 2-3, 9-11, 13-15, 18-19, 21, 23, 28, 30-32, 35, 37-38, and 40-43 have been canceled.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the CN202110650388.X application filed in the People’s Republic of China on June 10th, 2021.
Information Disclosure Statement
The Information Disclosure Statements filed on December 8th, 2023 and June 26th, 2025 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
Acknowledgement is made of the drawings received on December 8th, 2023. These drawings are acceptable.
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, 4-8, 12, 16-17, 20, 24-27, 29, 33-34, 36, 39, and 44 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 relieving and/or treating diarrhea or constipation by administering any of the CDK inhibitors recited at instant Claim 16, does not reasonably provide enablement for prevention of or relieving and/or treating any chemotherapy-associated gastrointestinal side effect in a subject by administering any CDK inhibitor. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of preventing, relieving, and/or treating chemotherapy-associated gastrointestinal side effects in a subject comprising administering a CDK inhibitor.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to the treatment of any gastrointestinal side effect associated with chemotherapy by administering any CDK inhibitor. This can include an array of known and unknown side effects classified as gastrointestinal side effects associated with chemotherapy. For example, what of a gastrointestinal side effect that is presently unknown to be associated with a chemotherapy that is discovered years from now to be associated with some presently unknown chemotherapy. Further, the breadth of CDK inhibitors encompassed by the claim includes all CDK inhibitors known presently, as well as any compounds either presently unknown, or later classified under the umbrella of CDK inhibitors. Can the Applicant simply “reach through” and obtain patent protection for a method of preventing, relieving, and/or treating a side effect that is either not known presently, or later is classified as a gastrointestinal side effect associated with chemotherapy, and can the Applicant “reach through” and obtain patent protection for the administration of compounds not yet discovered, but are later invented and classified as CDK inhibitors?
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
With respect to chemotherapy-associated gastrointestinal side effects, Shahid et. al., (“Cisplatin-induced gastrointestinal toxicity: An update on possible mechanisms and on available gastroprotective strategies, European Journal of Pharmacology, 49-57, 2018; hereinafter referred to as Shahid) represents the state of the prior art.
At the abstract, Shahid teaches administration of cisplatin is a widely prescribed chemotherapy, but its clinical use is limited due to the side effects, particularly at the gastrointestinal level that reduce the therapeutic efficacy of its administration. At Page 56, under Conclusion, Shahid states, “Gastrointestinal symptomatology predominates as the major lifelong clinical problem and contributes to delay and cessation of treatment regimen. Several mechanism of action including the generation of oxidative stress have been documented however the way these different pathways are integrated to induce remarkable gastrointestinal toxicity remains largely unknown. Combinatorial strategies to abrogate CP-induced gastrointestinal cytotoxicity have been attempted demonstrating partial protection.”
Taken together, Shahid demonstrates a lack of predictability in preventing gastrointestinal side effects resulting from administration of a chemotherapy. Though partial protection has been observed, it is established in the art that prevention of all gastrointestinal side effects associated with chemotherapy is highly unpredictable.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Beginning at Page 37 of the instant specification, numerous examples are provided, sufficiently demonstrating the efficacy of treatment of diarrhea and/or constipation by administration of the CDK inhibitors recited instantly at Claim 16. These examples are insufficient, however, to demonstrate prevention of diarrhea and/or constipation, much less prevention, relief from, and/or treatment of any gastrointestinal side effect associated with chemotherapy beyond diarrhea and constipation.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support the claims identifying the compounds by such composition or formula. See MPEP 608.1(p).
MPEP § 2164.01 (a) states, “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, 1556, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).”
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As referenced above, to practice the full scope of the instantly claimed invention, a person having ordinary skill in the art would need not only to identify CDK inhibitors beyond those instantly recited at Claim 16, but also identify and/or develop suitable metrics to evaluate these inhibitors for their efficacy in preventing, relieving, and/or treating chemotherapy-associated gastrointestinal side effects, with no assurance of success.
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.
The specification fails to provide enough support for the broad use of CDK inhibitors in preventing, relieving, and/or treating chemotherapy-associated gastrointestinal side effects beyond administration of those instantly recited at Claim 16 for the relief and/or treatment of diarrhea or constipation.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ 2d 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 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 having ordinary skill in the art would have to engage in undue experimentation to determine suitable CDK inhibitors to administer for the prevention, relief, and/or treatment of chemotherapy-associated gastrointestinal side effects, with no assurance of success.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-5, 16-17, 27, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Davis (WO 00/78299 A2; hereinafter referred to as Davis).
At the Abstract, Davis teaches a method for preventing/reducing the severity of epithelial cytotoxicity side effects, including mucositis in a subject receiving chemotherapy and/or radiation therapy by administering a CDK2 inhibitor. At Page 4, Last Paragraph of the instant specification, mucositis is listed as a gastrointestinal side effect for which the instantly claimed method may be used to treat.
At Page 1, First Paragraph, Davis names mucositis as a side effect of chemotherapy and/or radiation therapy. Further at Page 2, First Paragraph, Davis teaches mucositis is a common side effect of chemotherapy.
Regarding Claim 16, at Page 19, First Paragraph, Davis teaches roscovitine, as instantly recited, as a suitable CDK2 inhibitor for use in the prevention and/or treatment of mucositis.
Regarding Claim 17, Davis teaches at Claim 18 administration of a CDK2 inhibitor with a chemotherapeutic agent.
Regarding Claim 36, Davis teaches at Page 28, First Paragraph, the CDK2 inhibitor agents are suitable for administration in oral dosage forms.
Claims 1, 17, 20, 24, and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schmidt et. al. (“Protection against chemotherapy-induced cytotoxicity by cyclin-dependent kinase inhibitors (CKI) in CKI-responsive cells compared with CKI-unresponsive cells”, Oncogene, 20, 6164-6171, 2001; cited on Applicant’s Information Disclosure Statement filed December 8th, 2023; hereinafter referred to as Schmidt).
At Page 6164, right column, Schmidt teaches common cytotoxic side effects of chemotherapy include nausea, vomiting, and diarrhea.
At Page 6167, Last Paragraph, Schmidt teaches administration of CDK inhibitors (CKIs) to patients also receiving chemotherapy is useful in protecting normal cells from chemotherapy-induced cytotoxicity. Beginning at Page 6168, second column, Schmidt teaches administration of CKIs protected against cytotoxicity from the administration of cisplatin, instantly recited at Claim 20.
Double Patenting
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 72 of copending Application No. 18/860,264 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a method of preventing a chemotherapy-induced gastrointestinal side effect comprising administration of a CDK inhibitor.
The reference application is drawn to a narrower scope than the instant Claim 1, as the reference application is drawn to administration of compounds of the formula:
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The instant application is drawn to administration of any CDK inhibitor to prevent, relieve, or treat chemotherapy-associated gastrointestinal side effects. In the specification of the reference application, at Page 5, Paragraph 10, it is stated that “Provided herein is a method if inhibiting the activity of a cyclin dependent kinase (CDK), comprising contracting the CDK with an effective amount of a compound of Formula (I)”. Therefore, compounds of Formula (I), as recited in the reference application are CDK inhibitors. It follows that practicing the method claimed at reference Claim 72, then is drawn to preventing or ameliorating chemotherapy-associated gastrointestinal side effects by administering CDK inhibitors, and therefore, this claim reads on the instantly calimed method as recited at instant Claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 4-8, 12, 16-17, 20, 22, 24-27, 29, 33-34, 36, 39, and 44 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624