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 .
Duplicate Claims
Applicant is advised that should claim 13 be found allowable, claim 14 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
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 6-17 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. Claims 6-17 are directed to a treating a disorder where in the disorder is CLL, SLL or MLL. Specification identifies chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and Mantle cell lymphoma (MCL). There is no MLL defined in the specification, and it unclear what disease the claims refer to. In view of specification listing treatment of CLL, SLL and MCL (see page 4, lines 21-23), a reasonable interpretation is that MLL is MCL misspelled. To advance examination examiner will interpret the claims being directed to treatment of MCL.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claim(s) 1-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tam et al (New England Journal of Medicine, 2017, 378(13), 1211-1223) in view of Lapierre et al (US 9,630,968).
Scope of prior art
Tam teaches treatment of MCL by dual targeting of BTK and BCL2 with ibrutinib and Venetoclax (400mg) (page 1211, conclusions). Tam also teaches that preclinical models indicate that dual inhibition of BTK and BCL2 is synergistic (page 1212, column 2, lines 8-9). Tam reports the results of their study as being consistent with the notion that combination of ibrutinib and Venetoclax is highly effective in treatment of MCL (page 1221, column 2, lines 1-5).
Tam teaches that tumor lysis syndrome, which is increased toxicity resulting from rapid killing of cancer cells, is a concern and can be monitored for and avoided by administering one agent before the other (paragraph bridging pages 1212 and 1213). Tam administers Ibrutinib followed by Venetoclax.
Ascertaining the difference
All claims - Tam teaches combination of BTK and BCL2 in treatment of MCL and demonstrates Ibrutinib as BTK inhibitor. Current claims are directed to a different BTK inhibitor. Tam does not teach compound of formula (I) (also referred to as Nemtabrutinib or ARQ-531).
Claim 5 – Tam teaches administration of Venetoclax after BTK inhibitor, while claim 5 is directed to administration of Venetoclax before BTK inhibitor.
Secondary reference
Lapierre teaches compound of formula (I) having the same structure as the currently claimed compound of formula (I) and having activity as an inhibitor of BTK and in treatment of disorders associated with modulation of BTK (column 8, lines 36-48). In column 8, lines 59-61, Lapierre teaches compound of formula (I) is more potent than other known BTK inhibitors including Ibrutinib. In the paragraph bridging columns 23 and 24, Lapierre teaches that the dosage of the pharmaceutical composition should be sufficient to result in slowing or regressing the growth of the tumors and can be determined by a clinician.
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to use an alternative BTK inhibitor in the method of treating MCL taught by Tam. While Tam exemplifies ibrutinib as BTK inhibitor, the broader teaching is to advantages of a combination of BTK inhibitor and BCL2 inhibitor in treatment of MCL. It would have been obvious to prepare and administer a combination of ARQ-531 and Venetoclax instead of Ibrutinib and Venetoclax. Lapierre teaches ARQ-531 as a BTK inhibitor that can be used in treatment of BTK mediated diseases. Larierre also teaches ARQ-531 as a more potent BTK inhibitor than Ibrutinib thereby providing motivation to substitute one for the other.
Regarding order of administration:
Tam teaches tumor lysis syndrome being a concern in administration of Venetoclax and in administration of a combination of Venetoclax and Ibrutinib. The concern is rapid destruction of tumor cells causing toxicity. It would have been obvious to administer one agent observe the subject’s reaction and then to administer the other agent. Tam decides to administer Ibrutinib first. However, since there are only two possibilities, a skilled artisan would have readily realized the second possibility where Venetoclax is administered first.
Regarding effective dose:
Tam teaches a 400mg dose of venetoclax. With regards to ARQ-531, a skilled artisan would have found it obvious to determine the optimal dose effective to treat MCL in a subject in need,
Claim(s) 1-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over He (WO 2017/218844).
Scope of prior art
He teaches compositions comprising BTK inhibitor and BCL2 inhibitor (par [0036]) for treatment of lymphoid malignancy (par [0039]). The list of suitable BTK inhibitors includes ARQ-531 (par [0013]). The list of BCL2 inhibitors includes venetoclax (par [0018]). The list of lymphoid malignancies includes SLL, CLL and MCL (par [0033]). He teaches a significantly improved efficacy of the combinations compared to monotherapy (par [0064]).
Ascertaining the difference
He does not exemplify a composition comprising venetoclax and ARQ-531.
Obviousness
A skilled artisan would have found it obvious to prepare a composition comprising venetoclax and ARQ-531 and use it in a method of treating SLL, CLL or MCL in a subject in need thereof. While the specifically claimed combination is not exemplified, He teaches significant improvement in efficacy derived from administration of BTK and BCL2 inhibitors. A skilled artisan would expect similar improvement in efficacy over monotherapy, when other agents having BTK and BCL2 inhibitory activity are combined and used in treatment of malignancies. This includes the presently claimed combination of venetoclax and ARQ-531. In view teaching of He described above, it would have been obvious to try treating SLL, CLL or MCL in a subject in need by administering a pharmaceutical composition comprising venetoclax and ARQ-531.
With regards to effective dose, a skilled artisan would have found it obvious to determine an optimal safe and effective dose by routine experimentation.
Claim(s) 1-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shirley (Targeted oncology 2022, 17, 69-84; published online 12/14/2021).
Scope of prior art
Shirley is a review of BTK inhibitors in treatment of B-Cell Malignancies. Shirley teaches one strategy for treatment of CLL and SLL is combination treatment with a BTK inhibitor and Venetoclax (page 76, section 3.2.3 2nd paragraph; and throughout the whole document). Shirley also teaches ARQ-531 is a third generation BTK inhibitor which has the advantage of longer half-life (page 70, Table 1) and broader inhibition of additional kinases (page 71, column 1, third paragraph). Shirley also teaches combinations of BTK inhibitors with rituximab (paragraph bridging pages 71 and 72),
Ascertaining the difference
Shirley does not teach treatment of a subject by administering a combination of ARQ-531 and Venetoclax or ARQ-531 and rituximab.
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application would have found it obvious to prepare a pharmaceutical composition comprising ARQ-531 and Venetoclax and to try treating subjects with CLL or SLL by administering the composition. Shirley teaches that BTK inhibitors in co administered with Venetoclax are already used in treatment of CLL and SLL. Shirley also teaches ARQ-531 as a promising third generation BTK inhibitor that has favorable activity and pharmacokinetics. It would have been obvious to try to use ARQ-531 is a method where use of a BTK inhibitor is indicated. There is motivation because ARQ-531 has unique properties in CLL ans SLL treatment. There is suggestion because Shirley broadly teaches combinations of BTK inhibitors and Venetoclax. Lastly there is expectation of success based on the success of clinical studies with other BTK inhibitors. Same reasoning applies to combination of ARQ-531 and rituximab. Both agents are indicated in treatment of CLL and SLL and it would have been obvious to try combining the two to reap the benefits of combination treatment described by Shirley.
The specific administration schedule and doses can be determined by an artisan through routine experimentation. It would have been obvious to optimize doses and administration schedule with consideration given to clinical efficacy and safety.
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, 4, 5, 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 24, 30, 37, 40, 42 of copending Application No. 19/133,519 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘519 application claims treatment of MCL by administration of composition comprising nemtabrutinib and another agent.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-17 are pending
Claims 1-17 are rejected
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
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, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YEVGENY VALENROD/Primary Examiner, Art Unit 1628
Prosecution Insights