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 .
Priority
This application is a 371 of PCT/CN2022/102031 (06/28/2022)
and claims foreign priority to CHINA 202110722003.6 (06/28/2021)
CHINA 202111673614.2 (12/31/2021)
CHINA 202210693548.3 (06/17/2022).
Status
Claims 1, 11-14, 19, 21, 23-38 are pending. Claims 31-38 were newly presented.
Amended 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.
Claims 1, 2, 11, 23, 28, 35-38 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO2021110168, published 2021-06-10, citations to English equivalent US20230044606) (hereafter “Li’168”) in view of Li et al. (WO2019223632, published 2019-11-28) (hereafter “Li’632”).
Li’168 teaches ERK inhibitors as pharmaceutical compounds for treating tumors (Abstract, Fig. 1; [0060]; Example 4 p. 19-20)
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Li’168 teaches the compound is useful in both assay and in vivo testing showing high activity (p. 17-20).
Li’168 differs from instant claim 1’s Formula (I) by the right-hand side phenyl vs. 2-pyridyl.
Li’632 teaches ERK inhibitors as pharmaceutical compounds for treating cancer (Abstract, claim 21) of formula (I) (claim 1):
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including Examples 2 and 3:
2:
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; 3:
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(p. 66)
demonstrated as useful and tested in ERK2 assays (p. 80).
One of ordinary skill in the art of pharmaceutical development following the teaching of Li’168 would have considered the teaching of Li’632 in the same field of endeavor and recognize that the right-hand side phenyl of WX007 could be interchanged with 2-pyridyl and maintain ERK activity. One of ordinary skill in the art would have had a reasonable expectation of success based on the structural similarities of the compounds, identical utility, and experimental demonstrations among all of the compounds. Such modifications to pharmaceutical compounds is routine in the art as is demonstrated by the variations in the structure of the compounds in the cited references. Thus, one of ordinary skill in the art would have been motivated to develop the pharmaceutical for improved efficacy in treating tumors in the same manner and arrive at the claimed invention (i.e., Formula (I) with R7 as Cl) with a reasonable expectation of success. Thus, claims 1, 2, 11, 23, 28 are prima facie obvious.
Claims 12-14, 19, 21, 24-27, 29, 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO2021110168, published 2021-06-10, citations to English equivalent US20230044606) (hereafter “Li’168”) in view of Li et al. (WO2019223632, published 2019-11-28) (hereafter “Li’632”) as applied to claims 1, 2, 11, 23, 28 above and further in view of Patani et al. (Chem. Rev., 1996, Vol. 96, No. 8, P. 3147-3176).
Regarding claims 12, 26, and 29 to a compound of formula WX001, further differs from Li’168’s WX007 by a Cl vs. CH3 substitution on the right-hand side ring. However, Li’168 Li’168 teaches the genus:
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where R6 can vary among Cl and CH3 (claim 11). In addition, Li’168 teaches active species such as WX006 which differs from WX007 only by the substitution at the R6 position.
Patani teaches the well-known technique of bioisosterism in pharmaceutical development where Cl is substituted with CH3 with an expectation of similar biological activity (p. 3153-54).
Thus, in view of the
One of ordinary skill in the art of pharmaceutical development following the teaching of Li’168 would have also considered replacing the Cl group with a CH3 group at the same position because Li’168 teaches the substitution within the genus, both Li references teach compounds with substitutions at the same position were effective (Cl, F, CF3), and because it was a straightforward application of the well-known technique of bioisosterism as taught by Patani. One of ordinary skill in the art routinely makes such modifications and it is well within their technical grasp. Thus, the claims are prima facie obvious.
Regarding claims 13, 14, 19, 21, 24, 25, 27, 30-34 having language of the “crystal form” and “characterized by”, although the Li references teach crystal forms generically and the preparation of the compound including a solid, the references do not disclose the spectroscopic data (XRPD, DSC) of the instant claims. However, such properties are inherent in the product and are inseparable as stated in MPEP 2112.01:
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
…
“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
In this case, the prior art renders obvious the same compound and based on the disclosure would be in a solid form. This obvious compound has the identical structure as that of the instant claims. All solid forms possess an inherent X-ray diffraction pattern that only depends upon the manner in which the molecules are packed together. Similarly, all solid forms possess inherent DSC spectrum that depends on a variety of factors beyond how the molecules are packed together. The instantly claimed product is characterized by X-ray powder diffraction pattern data, and DSC data. Said data is inherent properties of the solid form.
The solid form of the prior art also possesses the inherent properties recited in the instant claims. The obvious compound and that in the instant claims are presumed to be the same compound because they have the same structure and chemical formula. The presumption allows a reasonable inference that they have identical inherent properties.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999); see MPEP 2112. Thus, the claiming of an unknown property inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Further, “the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product." Id. See also In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990) (“[W]hen the PTO shows sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.”)
For the reasons identified above, the Examiner has shown a sound basis for believing that the products of the applicant and the obvious prior art compound are the same, and met the burden of proving a prima facie case of inherency. The burden properly shifts to Applicants to prove that the prior art solid and the instantly claimed solid are not the same. Thus, claims 13, 14, 19, 21, 24, 25, 27, and 30 are prima facie obvious as per MPEP 2112.01 (“Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).”).
Response to Remarks - 35 USC § 103
Applicant argues “A POSITA would not have combined Li '168 and Li '632 to reach the instant invention”, “a POSITA would have recognized the substantial difference in the core structures of the compounds in Li' 168 and Li '632, and accordingly, would not have looked to Li '632 to modify WX007 of Li' 168.”
This argument is not persuasive because one of ordinary skill in the art would have considered the structural similarities and identical utility in weighing the combined teaching of the prior art. The core structures of both references differ by the presence of a ring nitrogen in a manner that one of ordinary skill in the art would expect to be analogous to modifying a pyridyl to a phenyl and thus preserve activity due to similar binding modes. Because the similar structures were effective for the same purpose would have motivated one of ordinary skill in the art to combine structural elements for the same purpose.
Applicant next argues that “Not only were compounds having a 2-pyridyl ring a very small fraction (less than 10%) of the compounds exemplified by Li '632, which weighs against the Examiner's assertion that a POSITA would have selected the 2-pyridyl ring, but more importantly, Li '632 clearly demonstrates that compounds having the 2-pyridyl moiety are inferior.” Therefore, POSITA would not have been motivated to combine the teachings and arrive at the claimed invention.
This argument is not persuasive because Li’168 demonstrated several experiments including in vivo that the compound was effective (Table 6, Fig. 1) which once of ordinary skill in the art would have considered as a lead compound for further development. One of ordinary skill in the art would have considered the teaching of Li’632 and found that activity persisted among changes to the right-hand-side of the molecule including among phenyl (2), pyridin-2-yl (3), pyridin-3-yl (4), thiazol-2-yl (5), pyriminidinyl (6), etc. (Tables 1-3) where Examples 2 and 3 had the highest levels of activity measured. Applicant points to Li’632’s example 12 as being inferior, but this compound differs in another way that example 2 does not, by an additional methyl side group on the methylene linker. Thus, Li’632 reasonably suggested interchanging phenyl to pyridin-2-yl (Ex 2 to 3) would maintain activity.
Applicant next argues that the claimed compounds display an unexpected properties of “pharmacokinetic characteristics” including an increase in Cmax and oral bioavailability (F%) and claims that “POSITA, after reading Li '168 and Li '632, would have in no way predicted such significant improvement in the instant compounds.”
This argument is not persuasive because it is unclear how the alleged unexpected result is actually unexpected and commensurate in scope with the claims. First, the single example WX001 in the specification does not establish the unexpected result for the entire scope of Formula (I). Second, the specification describes a number of results for the single compound (Cmax, F%): Table 24: 2500, 49%; Table 25: 921, 50%; Table 26: 1769, 60%. The forgoing results are not significantly different from the examples in Li’168. Thus, Applicant has not met their burden in establishing an unexpected result. MPEP 716.02(b), 2145.
Applicant argues in the same manner regarding the rejection further in view of Patani. The argument is also not persuasive for the same reasons above.
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, 11-14, 19, 21, 23-30-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of U.S. Patent No. 12398153 in view of Li et al. (WO2021110168, published 2021-06-10, citations to English equivalent US20230044606) (hereafter “Li’168”), Li et al. (WO2019223632, published 2019-11-28) (hereafter “Li’632”), and Patani et al. (Chem. Rev., 1996, Vol. 96, No. 8, P. 3147-3176) as applied in the 35 USC 103 rejection above. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent shares a disclosure with Li’168 and also claims WX007 which renders the instant claims obvious.
Response to Remarks - Double Patenting
Applicant argues in the same manner as in the 103 rejection above. The argument is also not persuasive for the same reasons above.
Applicant argues the '841 Patent does not share a common assignee, applicant, or joint inventor with the present application. This argument is persuasive and the rejection is withdrawn.
Conclusion
No claims allowed.
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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
