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 1-16, 18, 19 and 22 are pending in the application. Claims 1-4, 6-16 and 22 are rejected. Claims 1 and 7 are objected to. Claims 5, 18 and 19 are withdrawn.
Restriction/Election of Species
Applicant’s election without traverse of Group I, claims 1-16 and 22, and further elected species of “Compound 4” having the structure below in the reply filed on December 1, 2025 is acknowledged:
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Pursuant to MPEP § 803.02, the Markush claims that read on the elected species were examined fully with respect to the elected species. Upon examination, the elected species were found to be anticipated or rendered obvious by prior art; therefore, the Markush claim and claims to the elected species will be rejected. The claim(s) and subject matter that do not read on the elected species have NOT been examined and searched and are withdrawn from further consideration by the examiner.
Claims 1-4, 6-16 and 22 read on the elected species. Claims 5, 18 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 1, 2025.
Priority
This application is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/CN2021/141879, filed on December 28, 2021, which claims priority to International Application No. PCT/CN2020/140197, filed on December 28, 2020.
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.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) filed on September 22, 2023 is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the Examiner has considered the IDS documents and signed copies of the 1449 forms are attached.
Claim Objections
Claims 1 and 7 are objected to because of the following informalities:
Claim 1 should be amended to replace “Y selected” with -Y is selected- for sake of clarity and consistency. See last line of page 2 of 24.
Claim 7 should be amended to recite either a) “selected from the group consisting of...and 35...” or b) “selected from...or 35...” (i.e., include the word “and” or “or” before the last recited structure based on preamble language) for sake of proper Markush language.
Appropriate correction is required.
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 15 and 22 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.
Claim 15 recites the limitation “the level of leukocytes, T lymphocytes and B lymphocytes in the peripheral blood mononuclear cells” and is rejected as indefinite. There is insufficient antecedent basis for this limitation in the claim as parent claim 12 does not provide for levels of leukocytes, T lymphocytes, etc... or peripheral blood mononuclear cells. It is suggested Applicant replace “the level of leukocytes, T lymphocytes and B lymphocytes in the peripheral blood mononuclear cells” with “levels of leukocytes, T lymphocytes and B lymphocytes in
Claim 22 recites the expression “the periphery” and is rejected as indefinite. Neither parent claim 12 nor the specification defines this expression; therefore, it is unclear what “the periphery” is in reference to. For instance, it is unclear whether Applicant intended “the periphery” to mean a) the peripheral nervous system or b) an undefined area on the periphery of an undefined area of the subject. A claim that requires the exercise of subjective judgment without restriction may render the claim indefinite. In re Musgrave, 431 F.2d 882, 893, 167 USPQ 280, 289 (CCPA 1970).
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 1-4, 6-16 and 22 are rejected under 35 U.S.C. § 103 as being unpatentable over Wang et al. (PCT Publication No. WO 2018/027097 A1; February 8, 2018) in view of Sharief et al. (J Neuroimmunol. 2003, 134(1-2):158-166).
Determining the scope and contents of the prior art (See MPEP § 2141.01)
Wang et al. teach inhibitor compounds of “Bcl-2 proteins, e.g., Bcl-2 and/or Bcl-xL” such as Example 9 shown below. See e.g., paragraphs [0019] and [0301]).
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Wang et al. further teach methods of inhibiting Bcl-2 proteins comprising administering an effective amount of the disclosed prior art invention (e.g., Example 9) to a subject. See e.g., paragraph [0014].
Regarding instant claims 1-4, 6, 8 and 9, Example 9 as taught by Wang et al. is encompassed by variable definitions of the instantly claimed compound represented by Formula I, wherein A is “A-1”, further wherein R2 is -NO2, R2a is hydrogen and R3 is -N((heterocyclo)alkyl)(H); X1, X2, and X3 are each independently -CH; and Y is -CH2-. See e.g., paragraph [0301].
Regarding instant claim 7, Example 9 as taught by Wang et al. corresponds to Compound No. 4 as recited in the claim.
Regarding instant claim 11, Wang et al. disclose a “unit oral dose.” See e.g., paragraph [0163].
Regarding instant claims 12, Example 9 as taught by Wang et al. is encompassed by variable definitions of the instantly claimed compound represented by Formula I, wherein A is “A-1”, further wherein R2 is -NO2, R2a is hydrogen and R3 is -N((heterocyclo)alkyl)(H); X1, X2, and X3 are each independently -CH; and Y is -CH2-. See e.g., paragraph [0301].
Ascertainment of the differences between the prior art and the claims (See MPEP § 2141.02)
Regarding instant claims 1, 10, 12-16 and 22, Wang et al. does not explicitly teach methods of treating multiple sclerosis/reducing inflammation. Instead, Wang et al. mainly focus on methods for “selectively inhibit[ing] the activity of one type or a subset of Bcl-2 proteins for the treatment of hyperproliferative disease such as cancer.” See e.g., paragraph [0011]. However, it is noted that Wang et al. does not teach away from the instantly claimed methods of treating multiple sclerosis (MS) as evidenced by the disclosed combination therapy comprising “an agent for treating multiple sclerosis.” See e.g., paragraph [0210]. Notwithstanding, Sharief et al. teach “that [the] dysregulated expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of clinically active multiple sclerosis.” See e.g., the abstract. Sharief et al. further teach “that failure of apoptosis (programmed cell death)...may be involved in the pathogenesis of multiple sclerosis” and that there is “a significant increase in Bcl-XL [apoptotic] protein expression...[and relatively lower] cellular expression of the [pro-apoptotic][]-protein Bax in active MS.” See e.g., the abstract and page 160. Note: “Bax” appears to have been mislabeled as an “anti-apoptosis protein” on page 160 of the prior art. For example, see pages 159 and 162 of the prior art where “Bax” is accurately described as being pro-apoptotic. With respect to the limitations of instant claims 10, 12-16 and 22, Sharief et al. teach the following:
Regarding instant claims 10 and 16: Sharief et al. teach data obtained from “28 patients with relapsing-remitting MS.” See e.g., page 159.
Regarding instant claims 12-15 and 22: Sharief et al. associate multiple sclerosis (MS) with “a continuous cycle of inflammation within the CNS.” See e.g., page 158. Therefore, it can be reasonably expected that a method of treating MS would also result in reduced inflammation. Note: Instant claims 15 and 22 are drawn towards characteristics that would necessarily be present from administering the instantly claimed compound of Formula I, as recited in parent claim 12, to a MS patient population. Therefore, instant claims 15 and 22 do not further limit the scope of parent claim 1. See MPEP § 2112.01 which states: 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. “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).
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Considering that Wang et al. disclose the instantly claimed compound of Formula I as inhibitors of Bcl-2 proteins (e.g., Bcl-2 or Bcl-XL), it would have been obvious to a person of ordinary skill in the art to utilize the prior art Bcl-2 inhibitor compound (e.g., Example 9) in therapeutic methods deriving benefit from the inhibition of, for instance, anti-apoptotic Bcl-XL proteins. See e.g., paragraphs [0017] and [0018]. Therefore, in view of the teachings of Sharief et al. which teach “a significant reduction in the expression ratios of pro-apoptosis Bcl-2 proteins in patients with active MS when compared to patients with stable MS or the control group,” a skilled artisan would recognize the potential therapeutic benefit in increasing the expression ratios of pro-apoptotic Bcl-2 family proteins by decreasing (i.e., inhibiting) anti-apoptotic Bcl-2 proteins, such as Bcl-XL, in patients with active MS (e.g., relapsing-remitting MS). Therefore, at least in the interest of utilizing the Bcl-2 inhibitor compound of Wang et al. in methods of treating cancer or otherwise MS, a skilled artisan would be motivated to employ the instantly claimed methods.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
The analysis employed for an obviousness-type double patenting rejection parallels the analysis for a determination of obviousness under 35 U.S.C. § 103. 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 12, 13, 15 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 13, 16, 17-23 and 28 of copending U.S. Application No. 18/838,451 (’451). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 2, 4, 13, 16, 17-23 and 28 of ‘451 are drawn towards methods of preventing or treating an immune disease comprising administering the instantly claimed compound of Formula I. Furthermore, claim 4 of ‘451 recites “the immune disease is immune-mediated inflammatory disease” which is encompassed by the term “inflammation” as recited in instant claim 12.
Conclusion
No claims are allowed.
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/D.M.S./Examiner, Art Unit 1626
/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626