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 .
Claims 1 and 9-15 are pending.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Instant application is a U.S. National Stage entry of PCT/CN2021/116076, filed 09/01/2021. PCT/CN2021/116076 claims priority of foreign application CN202010889864.9, filed 08/28/2020. Therefore, the effective filing date is 08/28/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/28/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
For the sake of compact prosecution, claim 1 will interpreted as “A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof”.
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 9-15 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 for inhibiting mutant EGFR, does not reasonably provide enablement for treating or preventing EGFR-mediated diseases. 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.
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. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of inhibiting mutant EGFR and preventing or treating an EGFR-mediated disease in a patient, comprising administering a compound of the formula (I).
Nature of the invention
The nature of the invention is performance of a method of inhibiting EGFR and treating or preventing mutant EGFR-mediated diseases comprising administering the compound of formula I, shown below.
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State of the prior art
No single drug has been discovered that is effective in treating the myriad of EGFR-mediated diseases, including, but not limited to, “non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, glioblastoma, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer or multiple myeloma” (claim 15). See In re Hokum, 226 USPQ 353 (ComrPats 1985). No drug has been successful in the total prevention of any EGFR-mediated disease.
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of preventing or treating an EGFR-mediated disease in a patient, comprising administering a compound of formula I, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he 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).
The nature of the invention and predictability in the art, with specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] ...anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”.
The total prevention of any EGFR-mediated disease, to include the prevention of cancer as in instant claim 14, would be highly unpredictable, and has never been successfully proven using any drug in the art.
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using (performing) a method of preventing or treating an EGFR-mediated disease in a patient, comprising administering a compound of formula I. At best, on page 8 of the specification, and effective amount is described as “an amount effective to improve or eliminate one or more conditions”, wherein “such dosage may be administered as a single dose, or may be administered in accordance with an effective treatment regimen”. No guidance is provided for the “dosage” or “effective treatment regimen” that would be capable of treating or preventing every EGFR-mediated disease.
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of preventing or treating an EGFR-mediated disease in a patient, comprising administering a compound of formula I.
Similarly, according to the specification, compounds of formula I are capable of preventing and treating non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, glioblastoma, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer, and multiple myeloma.
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any of the aforementioned diseases. The specification only provides examples for inhibiting mutant EGFR comprising administering formula I. There is insufficient disclosure to reasonably conclude that the method of preventing or treating an EGFR-mediated disease in a patient, comprising administering the compound of formula I, as recited, would contribute to treatment of any the aforementioned diseases. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform hundreds of clinical trials and in vivo or in vitro assays in order to determine which diseases mediated by mutant EGFR would be treatable with formula I, or preventable, if prevention is possible. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of treating an EGFR-mediated disease in a patient, comprising administering the compound of formula I, is clearly justified.
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.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the administration of the compound of formula I.
Claim 1 is directed the use of a composition, which could be interpreted as a method claim with no method steps set forth.
For the sake of compact prosecution, claim 1 will interpreted as “A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof”.
Claims 9-13 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.
Regarding claims 11-13, the phrase "and the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
The inventor or joint inventor should note that claim 9 is a reach-through claim. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented. Similarly, the metes and bounds of the treatable or preventable EGFR-mediated diseases are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention.
The specification, on page 4, teaches that treatable or preventable EGFR-mediated diseases include “non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, glioblastoma, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer or multiple myeloma”. However, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments, including, but not limited to, the above listed diseases. Consequently, the method for the treatment or prophylaxis of an EGFR-mediated disease, the method comprising administering a compound of formula (I) has been rendered indefinite by the use of the reach-through protocol.
Claims 10-13 are rejected as being dependent upon claim 9 and failing to further specify the EGFR-mediated disease.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Rejections - 35 U.S.C. § 112(a), to overcome this rejection.
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.
Claims 1, 9, 10, 14, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (WO 2016192609 A1, hereinafter referred to as reference ‘609), cited by Applicant in the IDS (English translation provided).
Reference ‘069 teaches, in claims 5 and 6, a pharmaceutical composition comprising N-[3-[2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-7-oxo-6-phenyl-8(7H)-pteridinyl]phenyl]-2-propenamide (compound 14), as in instant claim 1. Claim 7 teaches a method of using said compound in the treatment or prevention of an EGFR mediated disease and in the inhibition of EGFR, as in instant claim 9.
Reference ‘069 teaches, in Example 3 and in Table 1, that compound 14 selectively inhibits the EGFR T790M and L858R mutations, which are EGFR exon 20 and exon 21 mutations, respectively, as in instant claim 10.
Claims 8 and 9 of reference ‘069 teach a method of treating cancer comprising administering said compound, wherein the cancer is non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, prostate cancer, glioma, ovarian cancer, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, pancreatic cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer, multiple myeloma or solid tumors, as in instant claims 14 and 15.
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 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO 2016192609 A1, hereinafter referred to as reference ‘609), as applied to claims 1-10, 14, and 15 above, and further in view of Yoon et al. (Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study, PLOS ONE, 13 February 2020, Vol. 15(2), e0228925, pages 1-14).
Reference ‘069 teaches, in Example 3 and in Table 1, that compound 14 selectively inhibits the EGFR T790M and L858R mutations, as in instant claim 10. See above rejection.
Reference ‘069 fails to teach a method of inhibiting EGFR mutations G719X, S768I, and L861Q, as in instant claims 11-13.
Yoon et al. investigated EGFR mutations in patients with lung adenocarcinoma. This study targeted the highest frequency of EGFR mutations, and excluded low frequency mutations (page 2, Methods). On page 4, it was taught that “[t]he target somatic mutations included E19 dels, E21 L858R mutation, E18 G719X mutation, E20 S768I mutation, E20 insertions, E20 T790M mutation, and E21 L861Q mutation.” It is also taught, on page 9, that treatment with tyrosine-kinase inhibitors leads to dramatically improved prognosis in patients with EGFR positive lung cancer.
Therefore, it would be prima facie obvious to use the growth factor receptor tyrosine kinase inhibitor taught by reference ‘069 et al. in the inhibition of G719X, S768I, and L861Q EGFR mutations, since reference ‘069 teaches inhibition of T790M and L858R mutations, and Yoon et al. teaches that tyrosine-kinase inhibitors lead to dramatically improved prognosis in patients with the EGFR mutations L858R, T790M, G719X, S768I, and L861Q. One of ordinary skill in the art would find it obvious to try administering a composition that is known to inhibit mutant EGFR on the most common EGFR mutations.
One of ordinary skill in the art would have a reasonable expectation of success administering a pharmaceutical composition known to inhibit mutant EGFR, specifically T790M and L858R mutations, in order to inhibit other common mutations, such as G719X, S768I, and L861Q.
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.
Claims 1, 9, 14, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 7-11 of U.S. Patent No. 11,306,095 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent ‘095 teaches, in claims 1, 2, and 7, a pharmaceutical composition comprising the compound of instant claim 1. Claims 8-11 teach a method of inhibiting EGFR comprising administering said compound, and a method of treating EGFR-mediated diseases, wherein the disease is non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, prostate cancer, glioblastoma, ovarian cancer, squamous cell carcinoma of head and neck, cervical cancer, esophageal cancer, liver cancer, kidney cancer, pancreas cancer, colon cancer, skin cancer, leukemia, lymphoma, stomach cancer, multiple myeloma, or solid tumors, as in instant claims 9, 14, and 15.
Conclusion
Claims 1 and 9-15 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 9-5.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624