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
This Office Action is responsive to the Response to Election/Restriction and Amendment filed 05/06/2026, that amended claims 2, 4-15, 17, and 20, and cancelled claims 1, 3, 16, 18-19, and 21.
Claims 2, 4-15, 17, and 20 are pending.
Priority
This application claims the following priority:
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Election/Restrictions
Applicant’s election without traverse of Group I, and entecavir monomaleate monohydrate as the reverse transcriptase inhibitor, in the reply filed on 05/06/2026 is acknowledged.
Claims 8-11 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and subject matter, there being no allowable generic or linking claim.
In the course of the search, the species of reverse transcriptase inhibitor was broadened to include entecavir monohydrate.
Claims 2, 4-7, 12-15 and 20 are examined on the merits herein.
Claim Objections
Claims 6 and 12 are objected to because of the following informalities:
-In claims 6 and 12, the phrase “capable of being,” should be deleted.
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 4 and 7 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.
-In claim 4, the phrase “entecavir hemihydrate to dihydrate” renders the claim indefinite. It is not clear if the “to” is a typo and should be “or,” or if this phrase is describing a compound that contains between half a mole of water (hemihydrate) to two moles of water (dihydrate) per mole of entecavir. This phrase is not further defined in the specification or the prior art.
For the purpose of applying prior art, this phrase is interpreted as “entecavir hemihydrate or dihydrate.”
-Regarding claim 7, the term "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
For the purpose of applying art, the subject matter following “preferably” is interpreted as exemplary of the dose, and as not further limiting the claim.
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 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.
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.
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.
Claims 2, 4, 13-15 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0282604 to Cuconati (published 2019, PTO-892) in view of WO 2019/185016 to Zhang (published 2019, IDS of 11/24/2024; US 2021/0017154 (IDS of 11/22/2024) relied upon as an English language translation of WO 2019/185016).
Cuconati teaches a composition comprising a capsid inhibitor and a reverse transcriptase inhibitor (pg. 85, claim 1).
Cuconati teaches entecavir and tenofovir as reverse transcriptase inhibitors (pg. 85, claims 36-37).
Cuconati exemplifies a combination of compound 3 and entecavir ([0357]), wherein compound 3 is a capsid inhibitor ([0057]-[0058]).
Cuconati teaches its compositions for the treatment of Hepatitis B (abstract).
Regarding claim 2, while Cuconati exemplifies a composition comprising a capsid inhibitor and entecavir, it differs from that of instant claim 2 in that it does not teach instant formula I as the capsid inhibitor.
Zhang specifically teaches capsid protein assembly inhibitors for the treatment of hepatitis B virus (HBV) infection (abstract; Original).
Zhang teaches the compound of instant formula I (pgs. 13, 20, 28; pg. 72, claim 19, Original; [0166]-[0169], Examples 11 & 12, Translation), wherein Examples 11 and 12 of Zhang are taught as having “A” anti-HBV activity, which correlates to an EC50 of less than or equal to 10nM, ([0350]).
Zhang exemplifies a method of treating HBV by administering compounds of instant Formula I, i.e., Examples 11 &12 of Zhang ([0361]-[0379], Translation)
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select instant formula I of Zhang, as the capsid inhibitor in the composition of Cuconati, to arrive at instant claim 2. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Cuconati teaches its capsid inhibitors as those that are capable of inhibiting the expression and/or function of a capsid protein either directly or indirectly,
-Zhang teaches compounds of instant formula I as inhibiting capsid protein assembly for the treatment of hepatitis B ([0069], [0071]-[0082]),
-both Cuconati and Zhang teach capsid inhibitors for the treatment of hepatitis B virus, and
-substituting equivalents known for the same purpose is prima facie obvious, see MPEP 2144.06.
As such, an ordinary skilled artis an would have been motivated to make such a selection, to predictably arrive at a therapeutically effective method of treating hepatitis B.
Regarding claim 4, Cuconati teaches entecavir hydrate as a form of entecavir for use in its compositions ([0380]).
Regarding claim 13, Zhang teaches a typical therapeutic dose of its compounds as about 1µg/kg to about 1g/kg, and preferably 0.01-100mg/kg per day, and exemplifies dosage amounts of 5, 20, and 30mg/kg ([0134], [0366], [0371], [0374], Translation); in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists, MPEP 2144.05.
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Regarding claim 14, Cuconati teaches administration of its compositions in the forms of tablets, capsules, pills, and more solid formulations, which are fixed combinations. Cuconati specifically teaches tablets or capsules in unit dosage form kits ([0251], [0253], [0268], [0274]).
Regarding claims 15 and 20, Cuconati teaches kits comprising a first container with one agent contained therein and a second container with a second agent contained therein to administer different dosage forms at different dosage intervals, which is a non-fixed combination ([0274]-[0277]).
Further regarding claim 20, Cuconati teaches its kits as further comprising a package insert ([0273]), instant part “(c);” where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art, MPEP 2112.01.
Claims 5-7, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0282604 to Cuconati (published 2019, PTO-892) in view of WO 2019/185016 to Zhang (published 2019, IDS of 11/24/2024; US 2021/0017154 (IDS of 11/22/2024) relied upon as an English language translation of WO 2019/185016), as applied to claims 2, 4, 13-15 and 20 above, and further in view of FDA Prescribing Information for Baraclude (published 2010, PTO-892).
Cuconati and Zhang are applied as discussed above and incorporated herein.
Regarding claim 5, while the combination of Cuconati and Zhang teaches a composition comprising a compound of formula I and entecavir, it differs from that of instant claim 5 in that it does not teach a dosage ratio of formula I to entecavir.
Cuconati further specifically teaches administering 50 or 100mg/kg to compound 3, a capsid inhibitor ([0331], [0336]).
FDA teaches administering 0.5-1mg of entecavir as tablets and 0.05mg/mL entecavir as an oral solution for the treatment of hepatitis B (pg. 1).
As such, an ordinary skilled artisan would have been motivated to modify the dosage and hence the ratio of the dosage amount of the compound of formula I to the dosage amount of entecavir, to arrive at instant claim 5. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Zhang teaches administration of 1µg/kg-1g/kg of its compounds, and exemplifies administering dosage amounts of 5, 20 and 30mg/kg of compounds of formula I for the treatment of hepatitis B,
-FDA teaches administering 0.5-1mg of entecavir as tablets and 0.05mg/mL entecavir for the treatment of hepatitis B, and
-"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," MPEP 2144.05(II).
As such, an ordinary skilled artisan would have been motivated to make such a modification, to predictably arrive at a pharmaceutical composition that is optimized to treat hepatitis B and minimize adverse side effects.
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Regarding claims 6 and 12, Cuconati exemplifies administration of its composition once or twice a day ([0331], [0336], [0361], [0392]); FDA teaches daily administration (pg. 1); and Zhang teaches daily administration ([0362], [0364]).
Regarding claim 7, FDA teaches administering 0.5-1mg of entecavir as tablets and 0.05mg/mL entecavir as an oral solution for the treatment of hepatitis B (pg. 1); in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622
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