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 .
Claim Objections
Claim 20 is objected to because of the following informalities: The claim refers to Table A in the specification. Appropriate correction is required.
2173.05(s) Reference to Figures or Tables [R-08.2012]
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. See MPEP § 608.01(m).
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.
Claim 23 is 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 23 is directed to a method of use of the compound of claim 1 in preparing RIPK1 selective inhibitors. The claim is unclear because the structure of inhibitors prepared from compound of claim 1 is not specified. Furthermore, according to the description, the compound of claim 1 is already a RIPK1 inhibitor. Additionally, the claim is a method claim, but fails to recite any steps that are required for carrying out the claimed method.
Claims 1-2 and 7-24 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 1 recites “the group S of substituents include:”. It is unclear if the term “include” limits the claim to the recited substituents (consisting of) or if the listed substituents represent only a portion of possible substituents (comprising).
Claims 1, 2 and 7-23 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. Claims include prodrugs of compound (I). The structure of said prodrugs is unclear.
Claim Rejections - 35 USC § 112(a) written description
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 1-2 and 7-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims comprise limitations directed to solvates.
With regards to solvates: Solvates are crystal forms where solvent molecules are included in the crystal matrix. Formation of any crystal form is highly unpredictable. Specification does not provide examples of any crystal forms not does it teach a skilled artisan how to prepare any crystal forms of the thousands of compounds within the scope of the claims. Due to unpredictably of crystal formation, examiner concludes that applicants did not have possession of solvates of compound 1 as the time of filing.
Claim Rejections - 35 USC § 112(a) enablement
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.
Claim 22 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The claims are enabled for treatment of a disease selected from inflammatory bowel disease, ulcerative colitis, Crohn’s disease, psoriasis, rheumatoid arthritis, and heart failure. However, the claims are not enabled from prevention of the above listed diseases.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
Nature of the invention and Breadth of the claims:
The claims are directed to a method of preventing a disease selected from inflammatory bowel disease, ulcerative colitis, Crohn’s disease, psoriasis, rheumatoid arthritis, and heart failure. The method comprises a step of administering compound of formula (I), an inhibitor of RIPK1, to a subject. The claims require a practitioner to identify a subject who is asymptomatic for the above listed diseases and to administer the active agent prophylactically in order to prevent development of the claimed disease.
State of the prior art and level of predictability in the art:
While there are strategies to delay onset of rheumatoid arthritis, there is currently no pharmaceutical agent that can with certainty prevent the disease. It is therefore highly unpredictable whether the currently claimed agent is capable of preventing development of RA.
Likewise, prophylactic treatment of psoriasis focuses on maintaining skin health.
Prophylactic treatment for inflammatory bowel disease, Crohn’s disease and ulcerative colitis focuses on maintaining remission of the disease, which does nor include subjects who have never had the disorder.
Chen et al (Frontiers in Pharmacology, 2022. DOI 10.3389/fphar.2022.976425) describes advances in RIPK1 kinase inhibitors including their pharmacological utility. Chen describes the role of RIPK1 in various types of diseases including inflammatory disease, ischemic injury, neurodegenerative disease and oncology (section 3). In section 4, starting on page 5, Chen describes various types of RIPK1 kinase inhibitors including GEN684, which is an inhibitor comprising bicyclic lactam moiety within the scope of current claims. On page 10, section 4.2.6, CGen describes GEN684 to be a type II RIPK1 which has demonstrated activity in controlling inflammation in various inflammatory disease models. Art suggests that the currently claimed RIPK1 inhibitor are enabled for treatment of disease in subjects who have are in need of treatment. However, art does not suggest prophylactic administration to subject who have not developed the disease.
Amount of direction provided by the inventor and existence of working examples:
Examples provided in the specification demonstrate RIPK1 inhibitory activity of the claimed compounds in in vitro studies. No examples demonstrating in vivo activity or activity in an established disease models are provided. With regards to treatment Chen (see above) provides sufficient evidence for enablement of claim directed to treatment. However, no preventative data is available.
Relative skill of those in the art and quantity of experimentation needed to make or use the invention:
A person ordinary skill would not be able to practice the method of preventing a disease selected from inflammatory bowel disease, ulcerative colitis, Crohn’s disease, psoriasis, rheumatoid arthritis, and heart failure by practicing the method of claim 22. The practice requires identification of asymptomatic subjects to whom compound of formula (I) is to be administered, determination of a dose suitable for prevention, and administration of a therapeutic agent to an asymptomatic subject. Whether a person will develop a disease with in the scope of claim 22 is highly unpredictable. While there are factors that might increase the likelihood of developing the disease, there is no certainty that it the individual will eventually become ill.
Thus, given these considerations, one of ordinary skill in the art clearly would not be able to practice the claimed method such that it can be used as contemplated in the specification without first engaging in substantial and undue experimentation. Therefore, the claims are rejected under 35 U.S.C. §112, first paragraph, as lacking and enabling disclosure.
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)}.
Genentech Inc. V. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 7, 8, 9, 10, 11, 12, 19 and 21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dow et al (J Med Chem, 2009, 52, 2652-2655; submitted by applicant on 12/8/23)).
On page 2653, Table 1, Dow discloses compounds 12f and 12h. In compound 12f, L2 = bond and R1 = cyclopentyl. In compound 12h R1-L2 is CH2CF3. Dow describes performing inhibition assays using the compounds and also further pharmacokinetic analysis of compound 12i, which is also within the scope of claim 1. Performing pharmacokinetic analysis meets the limitation directed to compound of claim 1 in a pharmaceutical composition.
Claim(s) 1, 8, 9, 12, 13, 17 and 24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CN 106032385 (submitted by applicant on 12/8/23).
Compound 2 on page 4 anticipates the rejected claims where R2 is monocyclic heteroaryl (claim 13)
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Compound 14 on page 5 anticipates the rejected claims where R2 is phenyl (claim 12)
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Compound 11 on page 5 anticipated the rejected claims where R2 is heterocycloalkyl (claim 17).
On page 18, art discloses preparation of compound 32 via ring closing reaction of intermediate 1, which is d-3 in the art. This disclosure anticipates the method of claim 24.
Claim(s) 1, 2, 7, 9, 10, 11, 12, 13, 18, 21, 22 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yogo et al (US 2018/0319819).
Yogo discloses compounds 69 and 73 (page 106). The compounds are within the scope of herein rejected claims. Yogo further discloses RIP1 kinase inhibitory activity of the compounds and treatment of inflammatory bowel disease (abstract). Yogo further tests the compounds in RIP1 inhibition assay by diluting the compound in assay buffer (paragraph [1113]). This meets the limitation directed to pharmaceutical composition of claim 21.
Claim(s) 1 and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al (US 10,562,902).
In column 137, Xu discloses compound 175, which anticipates the rejected claims.
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, 8, 9, 10, 11, 14, 15, 18 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 18 of copending Application No. 18/293,374 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because. Claim 1 of the ‘374 application discloses the currently claimed compound. Claim 18 of ‘374 discloses a pharmaceutical composition.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 8, 9, 10, 11, 14, 15, 18 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16 of copending Application No. 17,799,637 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because. Claim 1 of the ‘637 application discloses the currently claimed compound. Claim 16 of ‘374 discloses a method of treating of the same diseases as current claim 22.
Conclusion
Claims 1-2 and 7-24 are pending
Claims 1-2 and 7-24 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.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628