Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Claims 1-24 are currently pending.
Abstract
The abstract of the disclosure is objected to because “formule” should be corrected to read “formula”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 1-19, 22, and 24 are objected to because of the following informalities:
Claim 1 should standardize the punctation used to describe groups and substituents thereof. For example, “cyclohexyl;” in the definition of R2 should instead read “cyclohexyl,”.
Claims 1-19 recite variables with contrasting superscript and subscript modifiers. For example, Formula I depicts Ar1 but defines Ar1 instead.
Claims 2-3 should recite “formula” instead of “formulae”.
Claims 22 and 24 should read “any one of” instead of “any of”.
Claim 24 recites pharmaceutically acceptable salt twice.
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 22-23 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 treating PRMT5-mediated cancer, does not reasonably provide enablement for non-PRMT5-mediated 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.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention (1) and breadth of the claims (6)
The nature of the invention and breadth of Claims 22-23 is the treatment of cancers broadly, including particular localized cancers like colon and bladder.
The state of the prior art (2) and the predictability or lack thereof in the art (3)
Lattouf (Oncotarget, 2019, Vol. 10, (No. 34), pp: 3151-3153) teaches “our team recently showed that PRMT5 nuclear expression is associated with prolonged survival. These results corroborated findings in prostate cancer, in which the nuclear fraction of PRMT5 was responsible for inhibiting cell growth, while the cytoplasmic fraction promoted cell growth. In conclusion, this criterion should be evaluated prior to administering PRMT5 inhibitors, which may have adverse effects” (Abstract). “It would be of interest to understand the mechanisms involved in PRMT5 regulation in the nucleus of tumoral cells and to investigate whether its dual prognostic value can be extended to other cancers” (Page 3152, Last Para). One of skill in the art would not be able to reliably predict the treatment of non-PRMT5-associated cancers with the claimed compounds if the tumorigenic mechanisms and anti-cancer mechanisms conflict in the non-PRMT5-mediated tumor cells as taught by Lattouf.
The amount of direction or guidance present (4) and the presence or absence of working examples (5)
Applicant, in Table 26 beginning on Page 316, demonstrates the efficacy of the claimed compounds in colon cancer cells (HCT-116) wherein MTAP is reduced from the cell. The IC50 values are significantly lower as compared to the wild-type cells wherein MTAP is present to regulate PRMT5 activity. The MTAP null IC50 values are lower by orders of magnitude in most cases as compared to WT cells. Applicant has not shown how cancer with normally regulated PRMT5 activity is expected to be treated by the claimed inhibitors given that, in WT cells, MTAP is already plays an inhibitory role.
The quantity of experimentation needed (7) and the level of skill in the art (8)
Despite a very high level of skill in the oncological and pharmaceutical arts, the quantity of experimentation needed is extremely difficult, novel, and undue experimentation; the ability of the genus of Formula I and the extensive list of compounds in Claims 20-21 to treat cancers which may or may not be associated with PRMT5 activity is nearly impossible to determine and not enabled by the experiments disclosed in the specifications of the application.
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 1-24 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 regards as the invention.
Claim 1 is replete with lists within lists which inconsistently use semicolons and commas to delineate said items in each list of groups and substituents. For example, it is unclear whether the last group of R1 is substituted with halo or morpholinyl or morpholinyl is a distinct R1 group from C1-6 alkyl-O-C1-3 alkyl:
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. Claims 2-19 and 22-24 are rejected by virtue of dependency.
Claims 1 and 5-6 describe unsaturated ring members, X#, as being unsubstituted C. However, carbon is tetravalent, requiring an additional fourth bond to another atom or group outside of the ring. C is not a carbocation or anion and no charges are depicted on the drawn structure of Formula I. Claims 2-4, 7-19, and 22-24 are rejected by virtue of dependency.
Claims 20-21 recite “the tautomer thereof, the stereoisomer thereof, or the pharmaceutically acceptable salt”; however, “the” lacks antecedent basis. Claims 22-24 are rejected by virtue of dependency.
Allowable Subject Matter
The closest prior art is found in Walker (The Journal of Organic Chemistry 26(11): 4441-4455 1961). Walker teaches N, N'-Di(beta-phenylethyl)benzo[f]quinoline-b,6-dicarboxamide:
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(Page 4454, Para 1). The claimed genus of Formula I varies from the Walker compound in that one of the phenylethyl carboxamides is instead a primary amino group. This substitution is not taught or suggested by Walker and not an obvious modification. Therefore, the compounds encompassed by independent Claims 1 and 20-21 are free of the art.
Conclusion
No claim is allowable.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627