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
The instant application claims benefit to domestic provisional application No. 63/399,971 filed on August 22, 2022.
Status of Claims
Acknowledgement is made of original (1-7, 10-16) and amended (8-9) claims filed on November 11, 2023. Claims 1-16 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on February 13, 2023 and June 4, 2024 have been considered except where lined through. Cite No. 1 in the IDS filed 2/13/24 references CID 18378621, however the corresponding PubChem entry is not attached. Rather the attached PubChem reference is for 311324621 which does not appear relevant to instant application.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The title should reflect the structure of the compounds and their specific utility. The following title is suggested: 1,1-DIOXIDE-1,2,5-BENZOTHIADIAZEPINES FOR TREATING HDV/HBV INFECTION.
Claim Rejections - 35 USC § 112(a)
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 10-16 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.
Claim 10 recites “agents of distinct or unknown mechanism”, which is understood to read on any compound, molecule, polymer, or enzyme. The instant specification states “agents of distinct or unknown mechanism including agents that disrupt the function of other essential viral proteins or host proteins for HBV replication such as REP 2139, RG7834, and AB-452.” (see instant spec. at p. 19). The specification does not recite the structure necessary to achieve the claimed function. The recitation of three specific anti-HBV agents does not lead one skilled in the art to believe that applicant has possession of any and all compounds, molecules, polymers, or enzymes. The claim encompasses a multitude of components with different structures and different mechanisms of action (e.g. RG7834 or water or polyvinyl alcohol or adenosine deaminase), and there is nothing in the prior art to indicate any compound, molecule, polymer, or enzyme species can be used as a suitable alternative for another in the manner claimed.
Moreover, prior art Sagnelli et. al.1 teaches unpredictability for known HBV/HDV coinfection treatments; “the inadequacy of these therapeutic attempts is even more evident if compared with their poor tolerability and to the frequent serious adverse reactions entailed” (see Sagnelli at p. 11 ¶6).
Claims 11-16 are included in this rejection in view of their dependency from claim 10 as they do not cure its deficiencies and thus fail to comply with the written description requirement for the same reasons.
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 10-16 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.
Regarding claim 10, claim 10 recites “agents of distinct or unknown mechanism”. Claims 14-16 recite “antiviral compounds of distinct or unknown mechanism”. It is unclear if the claims encompass antiviral compounds which are not yet known, or not yet known to be antivirals. Accordingly, one skilled in the art would not know if any compound under the sun is infringing or not.
Claims 11-13 are included in this rejection because they depend from claim 10.
Further regarding claims 15-16, claim 15 recites “compared to the administering” and claim 16 recites “results in…than the treatment with”. The claim scope is variable and depends on an unknown standard (see MPM 2173.05(b)(II), noting that reference to a variable object may render a claim indefinite). In instant case the scope is unclear because the subjects may not be the same (e.g. cell vs human), the condition may not be the same (e.g. HBV vs HDV), and the methods do not exclude additional treatments being administered.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 98/02436 to Ding et. al.2
Ding teaches CAS# 202269-61-2 which reads on instant Formula I when L is N, Q1-Q4 are H, Z1, Z3, and Z4 are H, Z2 is aryl specifically phenyl (see Ding at Example 4 Step A at p. 24).
Ding CAS# 202269-61-2
Instant Formula I
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Claims 1-3, 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2017/222950 A1 to Walji et. al.3
Regarding claims 1-3, Walji teaches CAS# 2170611-15-9 (see Walji claim 21 at p. 82 lines 2-3 and at p. 52 Example 15). CAS# 2170611-15-9 reads on instant Formula I when L is C, Q1 and Q2 are taken together to form a 6 membered carbocyclic ring with 3 double bonds specifically phenyl leaving R14 and Q3 absent, Q4 is H, Z1, Z3, Z4 are H, Z2 is a substituted heteroaryl, specifically 1,2,4 oxadiazole.
Walji CAS# 2170611-15-9
Instant Formula I
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Regarding claim 8 and a composition, Walji teaches a pharmaceutical composition comprising a compound and an excipient (see Walji at claim 22).
Claims 1-5, 8-10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2023/164179 A1 to Yu et. al.4
Regarding claims 1-5 and a compound of Formula I or IX-3, Yu teaches compounds such as CAS# 2975163-89-2 (see Yu at p. 34 Example 1). CAS# 2975163-89-2 reads on instant Formula I when L is N, Q1 is C1-C6 alkyl specifically methyl, one of Q2 or Q3 is C1-6 alkyl specifically butyl the other is H, Q4 is aryl specifically phenyl, Z1, Z3, and Z4 are H, Z2 is a substituted aryl, specifically phenyl substituted with COOH.
Yu CAS# 2975163-89-2
Instant Formula I
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Regarding claim 8 and a pharmaceutical composition, Yu teaches pharmaceutical compositions (see Yu at claim 13).
Regarding claim 9 and a method of treating or preventing an HBV and/or HDV infection, Yu teaches a method of treating an HBV infection comprising administering a therapeutically effective amount of a compound (see Yu at claim 14). Yu also teaches a method of treating an HDV infection comprising administering a therapeutically effective amount of a compound (see Yu at claim 16). Yu also teaches a method of treating an HBV/HDV coinfection (see Yu at p. 31 ¶[0132]).
Regarding claim 10 and further comprising an additional therapeutic agent, Yu teaches the compositions may contain other compounds providing supplemental, additional, or enhanced therapeutic functions (see Yu at p. 8 ¶[0041]). Yu teaches further administering a therapy such as an HBV vaccine (see Yu at p. 31 ¶[0132]), reading on instant “therapeutic vaccine”.
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 6-7, 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Yu.
Regarding claims 6-7, Yu teaches CAS# 2975163-89-2 which reads on Formula I as discussed above.
Regarding claim 11 and co-formulated, Yu teaches the additional components may be co-administered together or separate (see Yu at p. 32 ¶[0133]).
Regarding claim 12 and co-administered, Yu teaches the additional components may be co-administered together or separate (see Yu at p. 32 ¶[0133]).
Regarding claim 13 and wherein the additional therapeutic agent is administered at a lower dose or frequency, Yu teaches the composition components may be less than the effective amounts of each compound administered monotherapies (see Yu at p. 32 ¶[0133]).
Regarding claim 14 and refractory patients, Yu teaches HBV is primarily treated with nucleotide analogs such as interferons, and notes nucleotide therapy may lead to antiviral drug resistant (see Yu at p. 1 ¶[0004]). Yu goes on to say there is a clear need for effective treatments for HBV (see Yu at p. 2 ¶[0006]). Yu states the instant disclosure is for treating HBV and/or HDV (see Yu at p. 3 ¶[0010]).
The prior art differs from the instant claims as follows: While Yu discusses drug resistance, Yu does not specify a method of claim 14. While Yu teaches CAS# 2975163-89-2, Yu does not specify a compound listed in claim 7. While Yu teaches compositions, Yu does not specify co-formulation.
However,
Regarding claim 11, one skilled in the art would appreciate that to co-administer together, the composition components would need to be co-formulated (see Yu at p. 32 ¶[0133]).
Regarding claims 6-7, Yu teaches Formula II (see Yu claim 1). Yu Formula II corresponds to instant Formula I as follows: Yu M is instant L, Yu R1 is instant Z2, Yu R4 is instant Z3, and Yu R5 is instant Q4.
Yu
Formula II
Instant
Formula I
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Yu CAS# 2975163-89-2 only differs from compounds of claim 7 through obvious alterations of H for F, or H for Cl, or isomeric alkyls.
Yu
CAS# 2975163-89-2
Instant
Compound 71
Instant
Compound 33
Instant
Compound 34
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Yu teaches R4 (instant Z3) may be a halogen (see Yu claim 1). Yu also teaches that R1 may be phenyl, optionally substituted with 1-3 substituents, including halogens (see Yu claim 1).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding claims 6-7 and H for halogen changes, Yu teaches these H for F or H for Cl swaps through Yu’s Formula II’s alternatives for R4 and substituted R1. One skilled in the art would thus appreciate these are suitable alternative changes for the disclosed compound species of Yu.
Regarding claim 7 and isomeric changes (butyl vs isobutyl), per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…isomers…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. Here, the prior art teaches highly similar structural isomers of the instantly claimed invention, wherein such isomers have the same, exact utility as the instantly claimed HBV/HDV treatments; accordingly, an artisan would readily appreciate that such compounds could be utilized in the treatment of an HBV and/or HDV infection, exactly as taught and suggested in view of the prior art.
Regarding claim 14 and refractory patients, one skilled in the art would recognize from Yu’s suggestive and motivational background disclosure (inventing compounds of Formula I in order to combat drug resistance in the art of treating HBV and/or HDV), that the compounds of Yu may be used in subjects resistant to existing treatments for HBV and/or HDV, including resistant to interferon treatment (see MPEP § 2143(I)(G)).
Furthermore, it is well-within the ordinary skill in art to incorporate a halogen in lieu of a hydrogen when suggested by the prior art. Furthermore, it is well-within the ordinary skill in art to make an isomer of a known compound. Furthermore it is well-within the ordinary skill in the art to recognize a motivational utility for discovery in the prior art, and apply the disclosed compounds for such a utility.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
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 1-6, 8-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17-26 of copending Application No. 18/582,8775 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-6 and compounds, when instant Z1, Z4, and Q2 are H and L is N, the scope of instant Formula I and App’877 Formula V-2 overlap (see App’877 claim 17). Instant Formula XVII (instant claim 5) overlaps with App’877 Formula XVII (App’877 claim 18).
App’877 Formula V-2
Instant
Formula I
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App’877 Formula XVII
Instant Formula XVII
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App’877 Compound 611
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Furthermore species claimed in App’877 read on instant Formula I (see App’877 claim 19). For example, App’877 Compound 611 reads on instant Formula I when L is N, Q1 is C1-C6 alkyl specifically methyl, Q2 is H, Q3 is C3-C8 cycloalkyl specifically cyclohexane, Q4 is aryl specifically phenyl, Z3 is halogen specifically chlorine, Z2 is a substituted 3-8 membered heterocycloalkyl specifically
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.
Regarding instant claim 8 and a composition, App’877 claims compositions comprising excipients (App’877 claim 20).
Regarding instant claim 9 and a method, App’877 claims a method of treating or preventing HBV and/or HDV (App’877 claim 21).
Regarding instant claim 10 and additional therapeutics, App’877 claims further administering therapeutic agents such as an HBV polymerase inhibitor (App’877 claim 22).
Regarding instant claims 11-12 and co-administering and co-formulating, App’877 claims co-administering and co-formulating with additional therapeutics (App’877 claims 23-24).
Regarding instant claim 13 and lower dose, App’877 claims the additional therapeutic is administered at a lower dose or frequency compared to when administered alone (App’877 claim 25).
Regarding instant claim 14 and refractory patient, App’877 claims wherein the subject is refractory to an additional therapy (App’877 claim 26).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 8-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-14 of copending Application No. 19/075,4106 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim 1-6 and compounds, When App’410 A or B is cyclic (C3-C8 cycloalkyl, C3-C8 cycloalkenyl, 3- to 8-membered heterocycloalkyl) and the other is absent, the limitations of App’410 Formula I overlap with instant Formula I (compare with instant Z2) (App’410 claims 1-2). App’410 Formula IX-2 and IX-4 further read on instant Formula I when instant Q3 is C3-C8 cycloalkyl specifically cyclohexane and L is N and Q1 is H or methyl (App’410 claim 3).
App’410 Formula I
Instant
Formula I
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App’410 Formula IX-2
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Regarding instant claim 8 and a composition, App’410 claims compositions comprising excipients (App’410 claim 6).
Regarding instant claim 9 and a method, App’410 claims a method of treating or preventing HBV and/or HDV (App’410 claim 7).
Regarding instant claim 10 and additional therapeutics, App’877 claims further administering therapeutic agents such as an HBV polymerase inhibitor (App’410 claim 8).
Regarding instant claims 11-12 and co-administering and co-formulating, App’410 claims co-administering and co-formulating with additional therapeutics (App’410 claims 9-10).
Regarding instant claim 13 and lower dose, App’410 claims the additional therapeutic is administered at a lower dose or frequency compared to when administered alone (App’410 claim 11).
Regarding instant claim 14 and refractory patient, App’410 claims wherein the subject is refractory to an additional therapy (App’410 claim 12).
Regarding instant claims 15-16, App’410 recites claims with the same limitations (App’410 claims 13-14).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-16 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Sagnelli et. al. “HBV/HDVCo-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges” Life 2021, 11, 169, 1-17. DOI: 10.3390/life11020169. Hereinafter Sagnelli.
2 Filed July 8, 1997. Published January 22, 1998. Hereinafter Ding.
3 Filed June 19, 2017. Published December 28, 2017. Hereinafter Walji.
4 Filed February 24, 2023. Published August 31, 2023. Priority to 63/314,104 filed February 25, 2022. No common Assignee or Inventor. Hereinafter Yu.
5 CIP of instant application. Hereinafter App’877.
6 Filed March 10, 2025. Hereinafter App’410.