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 .
This is the first action on the merits.
Claims 20-44 are pending and under consideration. Claims 1-12 and 16-19 have been cancelled and claims 20-44 are new claims.
Note: MPEP 608.01 states, “The pages of the specification including claims and abstract must be numbered consecutively, starting with 1, the numbers being centrally located above or preferably, below, the text.” Please number all pages in the claims.
Claim Rejections - 35 USC § 112
The rejection of claims 1-12 and 16-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for claims that refer to the specification are improper, is withdrawn based on the amendments.
The rejection of claims 1-12 and 16-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the phrase, “and/or, optionally, one of R1a or R1b and one of R2a or R2b together with the carbon atoms they are attached form a cyclopropane ring” is withdrawn based on the amendments.
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 20-44 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 pre-AIA the applicant regards as the invention.
Claims which depend from claim 20 which fail to remedy the deficiency of claim 1 are also rejected for the reasons set forth herein.
In claim 1, in the definition of R3, the phrase, “optionally substituted with -N(C1-4alkyl)2” is ambiguous. Does the optional substitution apply to all groups or only to the heterocyclyl group at the end of the definition?
In claims 24-26, the phrase, “each of which…” again is ambiguous. Does the phrase apply to all groups or only to the heterocyclyl group at the end of the definition?
Claims 33-35 lack antecedent basis based on the following group defined for R3:
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, see said group in claims 33 and 34; and compound II-21 in claim 35. Also note, the 112b rejection for claim 1 above.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
This is a new rejection based on the new claims.
Claims 36-41 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 a KRAS-mutated cancer, generally, does not reasonably provide enablement for treating and/or preventing cancer, generally. 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.
The how to use requirement of the enablement statute, when applied to method
claims, refers to operability and how to use the claimed method work. 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: (A) The
breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D)
The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount
of direction provided by the inventor; (G) The existence of working examples; and (H)
The quantity of experimentation needed to make or use the invention based on the
content of the disclosure, some experimentation is not fatal; the issue is whether the
amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444.
The pharmaceutical art is unpredictable. The specification does not enable any physician skilled in the art of medicine, to make the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
There are several biological assays: 1) binding to (mutated) KRAS inhibit the protein-protein interaction between SOS1 and (mutated) KRAS e.g., KRAS WT, KRAS G12C, KRAS G12D, KRAS G12V, KRAS G13D; 2) Ba/F3 cell model generation and proliferation assay with KRAS G12D, G12C and G12V; 3) NCI-H358 CTG proliferation assay (120 h) (NSCLC, G12C); 4) NCI-H2122 CTG proliferation assay (120 h) (NSCLC, G12C); 5) AsPC-1 CTG proliferation assay (120 h) (pancreatic cancer, G12D); 6) GP2D proliferation assay (120 h) (colorectal cancer, G12D); 7) SAS CTG proliferation assay (120 h) (HNSCC, wt amplified); 8) MKN1 CTG proliferation assay (120 h) (gastric cancer, wt amplified); 9) SK-CO-1 CTG proliferation assay (120 h) (CRC, G12V); 10) LOVO CTG proliferation assay (120 h) (CRC, G13D); 11) ERK Phosphorylation Assay with KRAS G12C; 12) Plasma Protein binding assay; 13) Mechanism based inhibition of CYP3A4 assay; 14) solubility assay and 15) Caco-2 assay.
The main issue here is the lack of any correlation between the inhibition of all wild-type or all mutated cancer cell lines and the treatment of all cancers generally, the lack of any pharmacological data, the predictability in the art, the state of the pharmacological arts and the breadth of the claims.
The scope of the claims involves all of the thousands of compounds of claim 1.
Thus, the scope of the claims is very broad.
Due to the level of unpredictability in the art, the very limited guidance provided, and the lack of working examples, the applicant has shown lack of enablement. 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, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
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.
Claim Rejections - 35 USC § 103
The rejection of claims 1-5, 7-12 and 17-19 under 35 U.S.C. 103 as being obvious over Broeker et al. (WO 2023099624), with a 102(a)(2) date, is withdrawn based on Applicant’s statement that “the cited wo 2023099624 PCT reference ("the '624 PCT") is not available as prior art to the claimed invention, and particularly is not available under 35 U.S.C. § 102(b)(2)(C). The '624 PCT is not available as prior art since the PCT on which the subject application is based, and the '624 PCT, each filed on November 30, 2022, were both commonly owned as of their effective filing date.”
The rejection of claims 1-5, 7-12 and 17-19 under 35 U.S.C. 103 as being obvious over Broeker et al. (WO 2023099612). with a 102(a)(2) date, is withdrawn based on Applicant’s statement that “The '612 PCT is not available as prior art since the PCT on which the subject application is based, and the '612 PCT, each filed on November 30, 2022, were both commonly owned as of their effective filing date. Therefore, the '612 PCT is not available as prior art under Sec § 102(a)(2).”
Double Patenting
The rejection of claims 1-5, 7-12 and 17-19 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-23, 30, 31 and 34-37 of U.S. Patent No. 12060367, is withdrawn based on the amended claims.
The provisional rejection of claims 1-5, 7-12 and 17-19 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 19-27 of copending Application No. 18755002, is withdrawn based on the amended claims.
No obviousness-type double patenting rejections over U.S. 12060367 and co-pending application 18755002 are being made because there is no overlap at the L-R3 group. Moreover, there is no teaching or guideposts pointing particularly to said group. Thus, the obviousness-type double patenting was considered but no longer applies based on the amended claims. The structural difference between the species of U.S. 12060367 and application 18755002 means that the two are patentably distinct.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
