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 1-17, submitted on 22 February 2024, represent all claims currently under consideration.
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 (i.e., changing from AIA to pre-AIA ) 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.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The effective filing date is 27 August 2021.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 22 February 2024, is acknowledged and has been considered.
Claim Objections
Claims 8-10 are objected to because of the following informalities: “the general formula according to claim 1” should read “the general formula II-A according to claim 1”. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: “the general formula according to claim 1” should read “the general formula VII-2 according to claim 11”. Appropriate correction is required.
Claim 13 is objected to because of the following informalities: “wherein the specific compounds are as follows” should read “wherein the compound is selected from” or similar. The claim should only be directed towards one compound. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 16 and 17 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 the treatment of cancers wherein aberrant EGFR activity is observed or wherein EGFR is mutated, does not reasonably provide enablement for all forms of cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth below:
The nature of the invention and breadth of the claims:
The claims are directed towards a method of treating cancer, comprising administering to a patient in need a therapeutically effective amount of a compound of Claim 1. The compounds of the invention are inhibitors of EGFR, and are shown to be effective in inhibiting mutated EGFR. Thus, the claims are directed to a method which can be used to treat all forms of cancer using the compounds of the invention to inhibit EGFR.
The state of the prior art and the predictability or unpredictability of the art:
Thomas (Frontiers in Oncology, August 2019, Volume 9, Article 800) provided a review of the epidermal growth factor receptor (EGFR) in cancer and current treatments targeting this receptor. EGFR is one of the most potent oncogenes that is commonly altered in cancers, and its activity has been serving as the primary target for developing cancer therapeutics. EGFR inhibitors have produced impressive therapeutic benefits to responsive types of cancers. However, acquired and innate resistances have precluded current anti-EGFR agents from offering sustainable benefits to initially responsive cancers and benefits to EGFR-positive cancers that are innately resistant (Abstract). Table 1 (Page 2) lists the cancers which commonly possess alterations of EGFR, and the current status of tyrosine kinase inhibitors in their treatment. As of publication, the only two forms of cancer of the 13 that are listed that are currently treated using tyrosine kinase inhibitors are non-small cell lung cancer and pancreatic, with marginal efficacy noted in pancreatic cancer. The authors state that this is due to the prevalence of mutations in those forms of cancer (Page 3). Murtuza (Cancer Research, 2019, 79 (4): 689-698) provides a review of EGFR-activating mutations in non-small cell lung cancer. Approximately 15-20% of patients with NSCLC have an EGFR-activating mutation. Currently there are several third-generation compounds which are at various stages of development for the treatment of EGFR-mutant NSCLC (Abstract). In view of these teachings, inhibition of EGFR can be used to treat certain cancers which possess aberrant EGFR activation, expression or activity. However, not all mutations of EGFR are responsive to treatment with EGFR inhibitors, and further, not all cancers possess aberrant EGFR activation or expression, and there is currently no known treatment that can be used to treat all forms of cancer.
The relative skill of those in the art:
The artisan would generally have an advanced degree related to the treatment or study of various cancers; however, their high level of training and knowledge would not be sufficient to overcome the lack of understanding of how to use the claimed compounds to treat all forms of cancer, as not all forms of cancer have mutated or aberrant EGFR.
The amount of direction or guidance presented and the presence or absence of working examples:
The compounds of the invention are inhibitors of epidermal growth factor receptor (EGFR). The specification demonstrates that compounds of the invention are capable of inhibiting the activity of mutant EGFR kinases (Test Example 1, Paragraph 0259), and that these compounds are capable of inhibiting the growth of cell lines which have EGFR mutations (Test Example 2, Paragraph 0264). However, the specification does not provide data demonstrating that these compounds are capable of treating all forms of cancer such as those which do not bear mutated EGFR.
The quantity of experimentation necessary:
Considering the state of the art as described above, in particular with regards to the lack of a panacea for the treatment of cancer due to the heterogenous nature of the disease, and the high unpredictability of the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate with the scope of the claims.
Claim Rejections - 35 USC § 112(b)
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 2-12 and 15 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. The of phrases such as “preferably”, “more preferably”, “even more preferably”, and the like renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Examiner suggests removing phrasing which uses “preferably” to overcome this rejection.
Claim 13 is 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. Claim 13 recites the limitation "the specific compounds" in Line 2. There is insufficient antecedent basis for this limitation in the claim as “the specific compounds” has not been defined previously.
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)(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 1-17 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Dineen (WO 2022/271630; Publication Date: 29 December 2022; Priority to 22 June 2021).
Dineen discloses compounds represented by structural formula I which are useful for treating a cancer (Abstract). The applicant has discovered novel compounds which are effective inhibitors of certain mutant forms of EGFR (Page 2, Summary). The present disclosure provides a compound represented by
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wherein Z is O or NH; A1, A2 and A3 are independently N or CR wherein R is H, halogen, or CH3; Ring A is C3-C6 cycloalkyl, C3-C6 cycloalkenyl, or 5-10 membered heteroaryl;
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; n is 0-6,
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, R3 and R4 are H or methyl;
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(Pages 3-4). The present disclosure provides a method of treating a subject with cancer, comprising administering to the subject an effective amount of a compound of the disclosure. In one embodiment, the cancer is non-small cell lung cancer (Page 4). In one embodiment, the cancer to be treated has EGFR L858R mutation and/or exon 19 deletion mutation and T7980M mutation. In another embodiment, the cancer to be treated may further have EGFR L858R mutation and/or exon 19 deletion mutation and the T790M mutation and C797S mutation (Page 4). Exemplary compounds include Example 2
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(Page 58), Example 10
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(Page 62), Example 11
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(Page 63), Example 12
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(Page 63), Example 13
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(Page 63), Example 14
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(Page 64), Examples 18 and 19
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(Page 66), Examples 20 and 21
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(Page 67), Example 22
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(Page 68), and Example 23
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(Page 69). Example 23 is identical to
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of examined Claim 12.These compounds have variable M1 as CH, variable M3 as N or CH, ring D as a 5- or 6-membered heteroaryl ring, and ring A as azetidinyl, with variables R1, R2, and R4 as different substituents which meet the limitations of what is claimed in the examined application. The compounds are shown to be inhibitors of different forms of mutated EGFR (Biological Example 1, Page 77; Table 2, Page 78).
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 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Dineen (WO 2022/271630; Publication Date: 29 December 2022; Priority to 22 June 2021) in view of Thornber (Chemical Society Reviews, Issue 4, 1979).
The teachings of Dineen are previously described and are fully incorporated into this rejection.
Dineen does not provide compounds wherein variable M1 is N, or does not disclose compounds identical to those of Claim 13 of the examined application.
Thornber teaches the concept of bioisosterism, which is the concept wherein groups or molecules which have chemical and physical similarities produce broadly similar biological properties (Page 563). Table 1 (Page 564) lists the classical isosteres, and includes ring equivalents. Such ring equivalents include -CH=CH-, =CH-, =N-, and S. These atoms have similar electronic properties and as such, their replacement within a ring system is not expected to significantly alter the properties of that ring.
Dineen and Thornber are considered analogous to the claimed invention as all are involved in the development of pharmaceuticals. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of Dineen by having variable M1 as N resulting in a 1,3,5-triazine as Dineen states that the compounds can have a 1,2,4-triazine as the heteroaromatic ring system. Thornber teaches that =N- and =CH- function as ring equivalents, and thus the artisan would not expect the properties of these compounds to be significantly altered by performing this substitution as due to the close chemical structure (See MPEP § 2144.09 I). Moreover, these two compounds are isomers of one another, and the artisan would not expect these compounds to have significantly different properties due to substituting one isomer for another.
Regarding Claim 13, the compounds 20/21 and 23 render several claimed compounds obvious.
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differs from Examples 20/21 of Dineen by absence of methyl group on the 5-membered heteroaromatic ring.
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differs from 23 by the presence of additional methyl on heteroaromatic ring.
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and
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differ from 23 by the addition of fluorine to central isoquinoline ring, which is disclosed as a potential modification by Dineen.
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each differ from 23 by removal of methyl and addition of chlorine, or addition of cyano or CF3 group, all of which are disclosed as potential modifications by Dineen.
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differs from 23 by addition of fluorine to ring.
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differs by addition of chlorine and methoxy group, which are modifications disclosed by Dineen. Several other compounds such as
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and
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differ from 23 by the substituent on the five-membered heteroaromatic ring. Each of these modifications are disclosed as potential modifications by Dineen. These compounds are prima facie obvious over the compounds of Dineen due to the close chemical structure, and by modifying the compounds within what is disclosed by Dineen, the artisan would not expect these compounds to have significantly different properties than what Dineen discloses (See MPEP § 2144.09 I). Table 2 (Page 79) shows that compounds 20 and 23 are both very potent inhibitors of mutated EGFR, providing both a motivation and a reasonable expectation of success in selecting these two compounds for modification within what is taught by Dineen.
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 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7, 8, 9, 11, 16, 18, and 19 of copending Application No. 18/847,626 (Amended Claims of 16 September 2024) (‘626).
Claim 1 of ‘626 is drawn to a compound of formula II-G
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wherein M1 is C, N, or CH, ring B is selected from a group which includes
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,
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. Claim 2 of ‘626 is directed to the compound of Claim 1, wherein the compound is further represented as formula VII-1
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wherein M5 is N or CH. Claim 7 of ‘626 is drawn to the compound of claim 1, further represented by the compound of general formula VII-2
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. Claim 8 of ‘626 is drawn to the compound of claim 7 further represented by the general formula VII-2-1
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. Claim 9 of ‘626 is drawn to the compound of claim 8, further represented by VII-2-1-1
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. Claim 11 of ‘626 is drawn to the compound of Claim 1 selected from several compounds including
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. Claim 16 of ‘626 is drawn to a method of treating cancer comprising administering a therapeutically effective amount of a compound of Claim 1. Claim 18 of ‘626 is drawn to the method of claim 16, wherein the cancer is non-small cell lung cancer. Claim 19 of ‘626 is drawn to the method of claim 16, wherein the cancer is a non-small cell lung cancer with EGFR mutations identical to those claimed in the examined applications.
The claims are not identical but are not patentably distinct because the compounds and methods of ‘626 read on the compounds and methods of the examined application. The specific compounds disclosed by ‘626 meet the limitations of the compounds of the examined application.
Regarding Claim 13, ‘626 does not disclose compounds identical to those which are claimed, but discloses compounds which are obvious modifications of what is claimed. For example,
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differs from
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of the examined application by the presence of an additional methyl group on the heteroaromatic ring, which is a possibility disclosed by ‘626. The artisan would not expect these compounds to have significantly different properties due to the close chemical structure (See MPEP § 2144.09 I).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
Prosecution Insights