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 .
Status of Application
The Amendments and Remarks filed on 02/26/26 are acknowledged.
Claims 1-3, 5, 7, 9-11, and 14 were amended.
New claims 16-17 were added.
Claims 1-17 are pending and included in the prosecution.
Response to Amendments/Terminal Disclaimer
Claim Objections
In light of the amendment of claims 3, 9, 10, and 14, the objections to these claims are withdrawn.
Rejection of claims under 35 USC § 112(b)
In light of the amendment of claims 2, 3, and 11 to remove the trademarks, the rejection of these claims under 35 USC § 112(b) is withdrawn.
Double Patenting Rejection
The terminal disclaimer filed on 02/26/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Patent Number 11,872,224 has been reviewed and is accepted. The terminal disclaimer has been recorded. The double patenting rejection is withdrawn.
New Rejection Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 16 is dependent on claim 15, and is ultimately dependent on claim 1 but recites the same limitations (the dosage range of about 5 mg to about 200 mg of Formula (II) or a pharmaceutically acceptable salt thereof) of claim 1. Even though claim 15 recites that the pharmaceutical composition is in a dosage form selected from a Markush group, the dosage range recited in claim 16 is the same as the dosage range of the pharmaceutical composition recited in claim 1. Claim 16 does not further limit claim 15. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Notice for all US Patent Applications filed on or after March 16, 2013
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.
Maintained Rejections
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 1-5, 8-10, and 14-15 are again rejected and new claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Hsu et al. (WO 2019/144089 A1 – “Hsu”) in view of Pathi et al. (WO 2022/054096 A1 – “Pathi”).
Instant claim 1 is drawn to a pharmaceutical composition comprising a solid dispersion, wherein the solid dispersion comprises:
i) a compound of Formula (II) or a pharmaceutically acceptable salt
thereof:
PNG
media_image1.png
350
402
media_image1.png
Greyscale
wherein G is hydrogen or -C(R2R2')-O-CO-O-R3, in which each of R2, and R2', independently, is hydrogen or C1-4 alkyl; R3 is C1-4 alkyl; the star (*) indicates a chiral center; and
ii) a pharmaceutically acceptable polymer,
wherein the pharmaceutically acceptable polymer is polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), or mixtures thereof,
wherein a weight ratio of the compound of Formula (II) or a pharmaceutically acceptable salt thereof to the pharmaceutically acceptable polymer is from about 1: 1 to about 1:5, and
wherein a therapeutically effective amount of the compound of Formula (II) or a pharmaceutically acceptable salt thereof is from about 5 mg to about 200 mg.
Hsu teaches a pharmaceutical composition containing compounds that have cap-dependent endonuclease inhibitory activity (Abstract). Compound 45, which reads on the claimed compound of is disclosed:
PNG
media_image2.png
726
520
media_image2.png
Greyscale
(Page 38, claims 1 and 15). The composition contains the compound and one or more pharmaceutically acceptable ingredients, which include diluents, disintegrants, binders, lubricants, glidants, surfactants, or a combination thereof (Page 4, lines 15-19). The composition can be administered orally (Page 5, lines 17-19) and includes capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions (Page 6, lines 12-14). “In the case of tablets, commonly used carriers include, among others, lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions or emulsions are administered orally, the active ingredient can be suspended or dissolved in an oily phase combined with emulsifying or suspending agents. If desired, certain sweetening, flavoring, or coloring agents can be added” (Page 6, lines 14-20). The composition is administered to treat influenza (Abstract). Example 3 discloses the survival rate of influenza virus 24 hours post-infection, and includes the oral administration of the compounds to mice at a dosage of 5, 10, or 20 mg/kg (Page 42, lines 11-14).
Hsu does not expressly teach a solid dispersion comprising a compound of Formula (II) and a pharmaceutically acceptable polymer wherein a weight ratio of the compound of Formula (II) or a pharmaceutically acceptable salt thereof to the pharmaceutically acceptable polymer is from about 1: 1 to about 1:5, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, HPC, HPMCAS, or mixtures thereof, and wherein the compound of Formula (II) or a pharmaceutically acceptable salt thereof is in a therapeutically effective amount from about 5 mg to about 200 mg.
Pathi teaches solid dispersions of Baloxavir marboxil in combination with one or more pharmaceutically acceptable carriers and pharmaceutical compositions comprising them (Page 1, 1st ¶, claims 1-4, 19, and 38). Baloxavir marboxil is disclosed as a cap-dependent endonuclease inhibitor for the treatment of influenza A or B (Page 2, 2nd ¶) and has the structure:
PNG
media_image3.png
586
856
media_image3.png
Greyscale
The solid dispersions may be formulated together with one or more pharmaceutically acceptable carrier, glidant, diluent, or excipient, as solid compositions for oral administration in the form of tablets, capsules, suspensions, dispersions, injectables, powders, granules or other pharmaceutical forms (Page 27, 4th ¶). Suitable water soluble carriers include polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶). Other preferred polymers include hydroxypropyl methylcellulose acetate succinate (HPMCAS) (Page 18, 2nd ¶, claims 4 and 19). Examples 4 and 10 disclose the preparations of amorphous solid dispersions of Baloxavir marboxil with HPMC AS (Pages 34 and 36). The weight ratio ranges of Baloxavir marboxil to polymer are from about 10:1 to about 1:10, and include about 1:4, about 1:3, about 1:2, or about 1:1 (Page 19, 2nd ¶).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a pharmaceutical composition containing Compound 45 which has cap-dependent endonuclease inhibitory activity for treating influenza, wherein the composition contains the compound and one or more pharmaceutically acceptable ingredients, and wherein the composition can be administered orally in the form of capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions, as taught by Hsu, in view of the solid dispersion of a structurally similar cap-dependent endonuclease inhibitor which is formulated with one or more pharmaceutically acceptable carriers for oral administration in the form of tablets, capsules, suspensions, dispersions, injectables, powders, granules or other pharmaceutical forms, wherein the carriers include polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers and HPMCAS, as taught by Pathi, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because both references teach pharmaceutical formulations for oral administration in the form of tablets, capsules, suspensions, and dispersions, and contain structurally similar cap-dependent endonuclease inhibitors along with pharmaceutically acceptable carriers. One of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Pathi because the latter teaches the same class of drug, i.e., cap-dependent endonuclease inhibitor, that is structurally similar, in the same type of composition, i.e., orally administrable tablets, capsules, suspensions, etc., with the same pharmaceutical excipients and for the treatment of the influenza. Moreover, according to MPEP 2141(III)(A), it is obvious to combine prior art elements according to known methods to yield predictable results.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 1, the limitation of a pharmaceutical composition comprising a solid dispersion would have been obvious over the pharmaceutical composition containing compounds that have cap-dependent endonuclease inhibitory activity (Abstract), wherein the composition can be administered orally (Page 5, lines 17-19) and includes capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions (Page 6, lines 12-14), as taught by Hsu, in view of the solid dispersions of Baloxavir marboxil in combination with one or more pharmaceutically acceptable carriers and pharmaceutical compositions comprising them (Page 1, 1st ¶, claims 1-4, 19, and 38), wherein the solid dispersions may be formulated as solid compositions for oral administration in the form of tablets, capsules, suspensions, dispersions, injectables, powders, granules or other pharmaceutical forms (Page 27, 4th ¶), as taught by Pathi.
Regarding instant claim 1, the limitation of a i) a compound of Formula (II) or a pharmaceutically acceptable salt thereof would have been obvious over Compound 45 (Page 38, claims 1 and 15), as taught by Hsu.
Regarding instant claim 1, the limitation of ii) a pharmaceutically acceptable polymer would have been obvious over polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶) and HPMCAS (Page 18, 2nd ¶, claims 4 and 19, Examples 4 and 10 - Pages 34 and 36), as taught by Pathi.
Regarding instant claim 1, the limitation of a weight ratio of the compound of Formula (II) or a pharmaceutically acceptable salt thereof to the pharmaceutically acceptable polymer which is from about 1:1 to about 1:5 would have been obvious over the overlapping weight ratio ranges of Baloxavir marboxil to polymer which are from about 10:1 to about 1:10, and include about 1:4, about 1:3, about 1:2, or about 1:1 (Page 19, 2nd ¶), and the ratio of 1:1 in Examples 4 and 10 (Pages 34 and 36), as taught by Pathi. One of ordinary skill in the art would have found it obvious to use the weight ratio of the cap-dependent endonuclease inhibitor of Formula 45 as taught by Hsu in the same weight ratio ranges taught by Pathi since both references teach structurally similar cap-dependent endonuclease inhibitors. According to MPEP 2144.05, “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.”
Regarding instant claims 1 and 16-17, the limitations of a therapeutically effective amount of the compound of Formula (II) or a pharmaceutically acceptable salt thereof from about 5 mg to about 200 mg (instant claim 1) and the dosage form containing from about 5 mg to about 200 mg (instant claim 16) and about 5 mg to about 100 mg (instant claim 17) would have been obvious over the oral administration of the compounds to mice at a dosage of 5, 10, or 20 mg/kg (Page 42, lines 11-14), as taught by Hsu, which lie within the claimed range. Please see MPEP 2144.05.
Regarding instant claim 2, the limitation of the compound of Formula (II) would have been obvious over Compound 45 (Page 38, claims 1 and 15), as taught by Hsu.
Regarding instant claim 3, the limitation of the pharmaceutically acceptable polymer would have been obvious over the polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶), and HPMC AS (Page 18, 2nd ¶, claims 4 and 19), as taught by Pathi. One of ordinary skill in the art would have found it obvious to use various commercially available grades of the HPMC AS polymer, which is taught by Pathi, in the composition unless there is evidence of criticality or unexpected results.
Regarding instant claim 4, the limitation of a weight ratio of the compound of Formula (II) or a pharmaceutically acceptable salt thereof to the pharmaceutically acceptable polymer which is from about 1:1 to about 1:3 would have been obvious over the weight ratio ranges of Baloxavir marboxil to polymer which are from about 1:3, about 1:2, or about 1:1 (Page 19, 2nd ¶), and the ratio of 1:1 in Examples 4 and 10 (Pages 34 and 36), as taught by Pathi. One of ordinary skill in the art would have found it obvious to use the weight ratio of the cap-dependent endonuclease inhibitor of Formula 45 as taught by Hsu in the same weight ratio ranges taught by Pathi since both references teach structurally similar cap-dependent endonuclease inhibitors.
Regarding instant claim 5, the limitation of the compound of Formula (II) or a pharmaceutically acceptable salt thereof in a therapeutically effective amount from about 5 mg to about 100 mg would have been obvious over the oral administration of the compounds to mice at a dosage of 5, 10, or 20 mg/kg (Page 42, lines 11-14), as taught by Hsu, which lie within the claimed range. Please see MPEP 2144.05.
Regarding instant claim 8, the limitation of the pharmaceutical composition further comprising one or more filler would have been obvious over the carriers and diluents including lactose (Page 6, lines 14-17), as taught by Hsu, and the diluent (Page 27, 4th ¶), as taught by Pathi.
Regarding instant claim 9, the limitations of the pharmaceutical composition further comprising one or more binder and/or disintegrant would have been obvious over the binders and disintegrants (Page 4, lines 17-19), as taught by Hsu, and the D-(+)-glucose, polyethylene glycol (PEG), povidone PVP K30, sodium carboxymethyl cellulose, alginates (Page 18, 3rd ¶), as taught by Pathi.
Regarding instant claim 10, the limitation of the filler would have been obvious over the lactose (Page 6, lines 14-17), as taught by Hsu, and the D-(+)-glucose (Page 18, 3rd ¶), as taught by Pathi. The limitation of the binder would have been obvious over the PEG and PVP K30 (Page 18, 3rd ¶), as taught by Pathi. The limitation of the disintegrant would have been obvious over the sodium carboxymethyl cellulose and alginates (Page 18, 3rd ¶), as taught by Pathi.
Regarding instant claim 14, the limitations of one or more pharmaceutically acceptable excipients would have been obvious over the pharmaceutically acceptable ingredients, which include diluents, disintegrants, binders, lubricants, glidants, surfactants, or a combination thereof (Page 4, lines 15-19), emulsifying or suspending agents, and sweetening, flavoring, or coloring agents (Page 6, lines 14-20), as taught by Hsu, and the pharmaceutically acceptable carrier, glidant, diluent, or excipient, as solid compositions for oral administration in the form of tablets, capsules, suspensions, dispersions, injectables, powders, granules or other pharmaceutical forms (Page 27, 4th ¶), as taught by Pathi.
Regarding instant claim 15, the limitations of the dosage form would have been obvious over the capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions (Page 6, lines 12-14), as taught by Hsu, and the tablets, capsules, suspensions, dispersions, injectables, powders, granules or other pharmaceutical forms (Page 27, 4th ¶), as taught by Pathi
Response to Arguments
Applicant’s arguments (Pages 6-9, filed 02/26/26) with respect to the rejection of claims 1-5, 8-10, and 14-15 under 35 U.S.C. 103 as being unpatentable over Hsu in view of Pathi have been fully considered but are not persuasive.
Applicant argues that the pharmaceutical composition of claim 1 enjoys beneficial effects of achieving markedly improved solubility while maintaining desired stability of the compound of Formula (II). Applicant points to Table 1 of Example 3 at pages 22-24 of the present specification which shows a substantially greater enhancement in solubility, and Example 4 of the present specification demonstrates that the solid dispersions prepared with the polymers according to claim 1 not only provide superior solubility but also exhibit favorable stability.
The examples in the instant specification have been fully considered but Applicant’s arguments are not persuasive because the enhancement in solubility and favorable stability that are attributed to the polymers recited in instant claim 1 would have been expected given the same polymers, i.e., polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶), and HPMC AS (Page 18, 2nd ¶, claims 4 and 19) are taught by Pathi.
Applicant has not presented unexpected results, particularly in the form of a direct comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. The showing of unexpected results must be commensurate in scope with the invention as claimed. See MPEP 716.02(d).
Applicant argues that Hsu is entirely silent with respect to any pharmaceutical formulation including such heterocyclic compounds, and Hsu neither teaches nor suggests combining the disclosed heterocyclic compounds with any excipient, carrier, or other formulation component.
The Examiner acknowledges that Hsu does not teach a solid dispersion comprising a compound of Formula (II) and a pharmaceutically acceptable polymer wherein a weight ratio of the compound of Formula (II) or a pharmaceutically acceptable salt thereof to the pharmaceutically acceptable polymer is from about 1: 1 to about 1:5, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, HPC, HPMCAS, or mixtures thereof, and wherein the compound of Formula (II) or a pharmaceutically acceptable salt thereof is in a therapeutically effective amount from about 5 mg to about 200 mg. However, Hsu teaches a pharmaceutical composition containing compounds that have cap-dependent endonuclease inhibitory activity (Abstract). Hsu teaches that the composition contains the compound and one or more pharmaceutically acceptable ingredients, which include diluents, disintegrants, binders, lubricants, glidants, surfactants, or a combination thereof (Page 4, lines 15-19). The composition can be administered orally (Page 5, lines 17-19) and includes capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions (Page 6, lines 12-14). Commonly used carriers, lubricating agents, diluents, oily phases, sweetening, flavoring, or coloring agents are disclosed (Page 6, lines 14-20).
The deficiency in Hsu regarding water soluble carriers including polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶) and HPMCAS (Page 18, 2nd ¶, claims 4 and 19) is cured by Pathi. The teachings of Hsu and Pathi are properly combined because both references teach dispersions, tablets, capsules, suspensions, etc., and structurally similar cap-dependent endonuclease inhibitors along with pharmaceutically acceptable carriers. One of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Pathi because the latter teaches the same class of drug, i.e., cap-dependent endonuclease inhibitor, that is structurally similar, in the same type of composition, i.e., orally administrable tablets, capsules, suspensions, etc., with the same pharmaceutical excipients and for the treatment of the influenza. Moreover, according to MPEP 2141(III)(A), it is obvious to combine prior art elements according to known methods to yield predictable results.
Also, one of ordinary skill in the art would have found it obvious to try and include the cap-dependent endonuclease inhibitor Compound 45 of Hsu in various compositions, including the solid dispersion of Pathi which includes a compound from the same class of drug, i.e., cap-dependent endonuclease inhibitor, and have a reasonable expectation of success in producing a functional composition containing Compound 45 of Hsu. Please see MPEP 2141(III)(E) which states that it is obvious to try choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success.
Applicant argues that Pathi relates to formulations of Baloxavir marboxil which is a compound structurally distinct from the compound of Formula (II).
This is not persuasive because even though baloxavir marboxil is not identical to the compound of Formula (II) as recited in instant claim 1, baloxavir marboxil is disclosed by Pathi to be in the same class of cap-dependent endonuclease inhibitors for the treatment of influenza A or B (Page 2, 2nd ¶). One of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Pathi because the latter teaches the same class of drug, i.e., cap-dependent endonuclease inhibitor, that is structurally similar, in the same type of composition.
Applicant argues that although Pathi generally mentions that various polymers may be used for preparing solid dispersions, the actual experimental disclosure of Pathi is limited to evaluating the solubility of solid dispersions including baloxavir marboxil and Kollidon® VA64, or Eudragit®, as described in Example 16 in Pathi. Applicant argues that the polymers demonstrated in Pathi as providing improved solubility are limited to Kollidon® VA64 and Eudragit®, neither of which falls within the specific pharmaceutically acceptable polymers recited in claim 1.
This is not persuasive because Pathi clearly teaches that suitable water soluble carriers include polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶). Pathi also teaches that other preferred polymers include HPMCAS (Page 18, 2nd ¶, claims 4 and 19); and Examples 4 and 10 disclose the preparations of amorphous solid dispersions of Baloxavir marboxil with HPMC AS (Pages 34 and 36). Moreover, according to MPEP § 2123, “a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” and “disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure of preferred embodiments.”
Applicant argues that: “With a knowledge in the art that the suitable combination of drugs and polymers to prepare a solid dispersion is drug-specific, as discussed above, a person having ordinary skill in the art would not have been motivated to combine the compound of Formula (II) with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), or mixtures thereof, much less at the ratio of from about 1: 1 to about 1: 5 as recited by claim 1.”
This is not persuasive because both Hsu and Pathi teach the same form of compositions, i.e., dispersions, tablets, capsules, suspensions, etc., and the same class of active ingredients, i.e., structurally similar cap-dependent endonuclease inhibitors, along with the same pharmaceutically acceptable carriers. One of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Pathi because the latter teaches the same class of drug, i.e., cap-dependent endonuclease inhibitor, that is structurally similar, in the same type of composition, i.e., orally administrable tablets, capsules, suspensions, etc., with the same pharmaceutical excipients and for the treatment of the same condition, i.e., influenza.
Applicant argues that a person having ordinary skill in the art also would not have expected the beneficial effect such a combination at the recited ratios would provide. Neither Hsu nor Pathi provides any teaching or information regarding the interactions between the heterocyclic compounds disclosed in Hsu and the polymers evaluated in Pathi. Applicant argues that there is no reason to assume that a person of ordinary skill in the art based on the disclosures in Hsu and Pathi, would have a reasonable expectation that the heterocyclic compounds of Hsu could be formulated with the polymers exemplified in Pathi to form a solid dispersion exhibiting suitable solubility, let alone arrive at the markedly improved solubility and stability achieved by features of the composition required by claim 1.
This is not persuasive because the beneficial effects of the combination of the active compound of Formula (II) and the recited polymers in the recited ratios would have been expected given the same types of compositions taught by both Hsu and Pathi. Applicant argues beneficial effects whereas unexpected results compared to the closest prior art are required to provide evidence of non-obviousness.
Therefore, the rejection of 11/28/25 is maintained.
Claim Rejections - 35 USC § 103
Claims 6-7 and 11-13 are again rejected under 35 U.S.C. 103 as being unpatentable over Hsu et al. (WO 2019/144089 A1 – “Hsu”) in view of Pathi et al. (WO 2022/054096 A1 – “Pathi”), as applied to claims 1-5, 8-10, and 14-15 above, further in view of Chal et al. (US 2014/0212491 A1 – “Chal”).
Instant claim 6 is drawn to the pharmaceutical composition according to claim 1, wherein the solid dispersion is present at a concentration from about 3% w/w to about 40% w/w.
The teachings of Hsu and Pathi are discussed above.
Hsu and Pathi do not expressly teach that the solid dispersion is present at a concentration from about 3% w/w to about 40% w/w.
Chal teaches a pharmaceutical composition having an effective amount of substantially amorphous antiviral compound ledipasvir formulated as a solid dispersion comprising ledipasvir dispersed within a polymer matrix formed by a pharmaceutically acceptable polymer (claims 1 and 2). The polymer is copovidone (claim 6). The pharmaceutical composition comprises about 18% w/w of the solid dispersion comprising ledipasvir (claim 68). Table 16 discloses the d90 particle size of the ledipasvir solid dispersion of 44 µm (Page 24). The pharmaceutical compositions are usually administered orally ([0097]) via capsule or tablet ([0098]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a pharmaceutical composition containing Compound 45 which has cap-dependent endonuclease inhibitory activity for treating influenza, wherein the composition contains the compound and one or more pharmaceutically acceptable ingredients, and wherein the composition can be administered orally in the form of capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions, as taught by Hsu, in view of the solid dispersion of a structurally similar cap-dependent endonuclease inhibitor which is formulated with one or more pharmaceutically acceptable carriers for oral administration in the form of tablets, capsules, suspensions, dispersions, injectables, powders, granules or other pharmaceutical forms, wherein the carriers include polymers such as polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers and HPMC AS, as taught by Pathi, further in view of the pharmaceutical composition having an effective amount of substantially amorphous antiviral compound formulated as a solid dispersion comprising the antiviral compound dispersed within a polymer matrix formed by a pharmaceutically acceptable polymer, wherein the polymer is copovidone and the pharmaceutical composition comprises about 18% w/w of the solid dispersion comprising the antiviral compound, as taught by Chal, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because all three references teach pharmaceutical formulations for oral administration in the form of tablets, capsules, suspensions, and dispersions, and contain antiviral compounds along with pharmaceutically acceptable carriers. One of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Pathi because the latter teaches the same class of drug, i.e., cap-dependent endonuclease inhibitor, that is structurally similar, in the same type of composition, i.e., orally administrable tablets, capsules, suspensions, etc., with the same pharmaceutical excipients and for the treatment of the influenza. Furthermore, one of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Chal because the latter reference teaches the advantage of the amorphous solid dispersion including acceptable stability, physical characteristics, in vivo performance, and improved biopharmaceutical performance ([0233]). Additionally, Chal teaches the advantage of the solid dispersions of the antiviral compound related to improved in vivo and in vitro performance and maufacturability/scalability relative to other formulation approaches, such as wet and dry granulation formulations ([0056], [0213]). Moreover, according to MPEP 2141(III)(A), it is obvious to combine prior art elements according to known methods to yield predictable results.
Regarding instant claims 6, 12, and 13, the limitations of the solid dispersion present at a concentration from about 3% w/w to about 40% w/w would have been obvious over the dispersions (Page 6, lines 12-14), Compound 45 (Page 38, claims 1 and 15), as taught by Hsu, in view of the solid dispersions of the anti-influenza antiviral compound Baloxavir marboxil (Page 27, 4th ¶), as taught by Pathi, and the pharmaceutical composition comprising about 18% w/w of the solid dispersion comprising the antiviral compound (claim 68), as taught by Chal.
Regarding instant claim 7, the limitation of the solid dispersion having a D90 particle size in a range of about 15 µm to about 50 µm would have been obvious over the d90 particle size of the antiviral compound containing solid dispersion of 44 µm (Page 24 - Table 16), as taught by Chal.
Regarding instant claim 11, the limitation of the filler would have been obvious over the mannitol and microcrystalline cellulose (MCC) ([0034] and [0101]), as taught by Chal. The limitation of the binder would have been obvious over the HPC, HPMC, and povidone ([0035]), as taught by Chal. The limitation of the disintegrant would have been obvious over the croscarmellose sodium, crospovidone, and pregelatinized starch ([0035]), as taught by Chal.
Regarding instant claims 12 and 13, the limitations of the filler present at a concentration of from about 40% w/w to about 95% w/w would have been obvious over the diluents mannitol, MCC, lactose, and lactose monohydrate ([0034] and [0101]) and the lactose monohydrate included in an overlapping amount of about 1 to about 50% w/w ([0102]), as taught by Chal. Please see MPEP 2144.05 regarding the obviousness of ranges.
Regarding instant claim 13, the limitation of the binder and/or disintegrant present at a concentration of from about 1% w/w to about 35% w/w would have been obvious over the disintegrant croscarmellose sodium present in an amount from about 1 to about 10% w/w ([0118]), as taught by Chal. Please see MPEP 2144.05 regarding the obviousness of ranges.
Response to Arguments
Applicant’s arguments (Page 9, filed 02/26/26) with respect to the rejection of claims 6-7 and 11-13 under 35 U.S.C. 103 as being unpatentable over Hsu in view of Pathi and Chal have been fully considered but are not persuasive.
Applicant argues that Chal fails to teach or suggest the specific polymers recited in claim 1, and therefore does not remedy the deficiencies of Hsu and Pathi discussed above.
This is not persuasive because the specific polymers recited in claim 1 are rendered obvious by the polyvinyl caprolactam-polyvinyl acetate polyethylene glycol copolymers (e.g. Soluplus™) (Page 18, 3rd ¶) and HPMCAS (Page 18, 2nd ¶, claims 4 and 19) taught by Pathi. The propriety of combining the teachings of Hsu and Pathi is discussed in detail above. Chal is used for curing the deficiency of the solid dispersion is present at a concentration from about 3% w/w to about 40% w/w. The teachings of Hsu, Pathi, and Chal are properly combined because all three references teach pharmaceutical formulations for oral administration in the form of tablets, capsules, suspensions, and dispersions, and contain antiviral compounds along with pharmaceutically acceptable carriers. One of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Pathi because the latter teaches the same class of drug, i.e., cap-dependent endonuclease inhibitor, that is structurally similar, in the same type of composition, i.e., orally administrable tablets, capsules, suspensions, etc., with the same pharmaceutical excipients and for the treatment of the influenza. Furthermore, one of ordinary skill in the art would have found it obvious to use the cap-dependent endonuclease inhibitor Compound 45 of Hsu in the solid dispersion of Chal because the latter reference teaches the advantage of the amorphous solid dispersion including acceptable stability, physical characteristics, in vivo performance, and improved biopharmaceutical performance ([0233]). Additionally, Chal teaches the advantage of the solid dispersions of the antiviral compound related to improved in vivo and in vitro performance and maufacturability/scalability relative to other formulation approaches, such as wet and dry granulation formulations ([0056], [0213]). Moreover, according to MPEP 2141(III)(A), it is obvious to combine prior art elements according to known methods to yield predictable results.
Therefore, the rejection of 11/28/25 is maintained.
Conclusion
No claims are allowed.
Since this new rejection was necessitated by applicant’s amendment, THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARADHANA SASAN whose telephone number is (571)272-9022. The examiner can normally be reached Monday to Friday from 6:30 am to 3:00 pm.
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, Robert A. Wax can be reached on 571-272-6023. 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.
/ARADHANA SASAN/Primary Examiner, Art Unit 1615
Prosecution Insights