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 . 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.
Priority
The instant application is a 371 of PCT/GB2021/052199 filed on 08/24/2021 and claims foreign priority to British application no. GB2105404.4 filed on 04/15/2021, GB2019097.1 filed on 12/03/2020, and GB2013221.3 filed on 08/24/2020. The certified copies of the foreign priority applications filed on 02/24/2023 are acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/28/2023, 02/27/2025, and 05/13/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 07/14/2023 is acknowledged. Claims 1-39 are cancelled. Claims 40-59 are newly added.
Accordingly, claims 40-59 are pending and being examined on the merits herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Page 2 lines 33-34 recites the link https://www.sigmaaldrich.com/catalog/product/aldrich/448869?lang=en®ion=GB&g clid=EAIalQobChMI8J7GkdG76gIVEO7tCH3YZgTwEAAYAiAAEgKVKPD_BwE, Page 3 line 7 recites the link https://doi.org/10.1101/2020.03.29.014183, and Page 17 line 18 recites the link https://www.european-virus-archive.com. The bolded portions in each of the links are not allowed in the specification.
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
The structural formula recited in claim 40 is being interpreted as a block copolymer having the recited monomer units connected in the order that is shown in the formula with varying mole % as recited for each of the units.
Therefore, the scope of claim 40 does not include an amphiphilic carbohydrate compound that has the monomer units in any arrangement or entirely random as recited in page 8, lines 7-12 of the instant specification (“The amphiphilic carbohydrate compound used in this invention is a chitosan derivative. With reference to the formula in this invention, all percentages refer to mole %. In formula I, it is understood that A + D + H + Q + T will be equal to 100%. It should also be understood that A, D, H, Q, and T may form any arrangement in the amphiphilic carbohydrate compound. The arrangement may therefore be entirely random or as a block copolymer form such as ADHQTADHQT etc.”).
Claim Rejections - 35 USC § 112
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 40-59 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a viral infection, does not reasonably provide enablement for preventing viral infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples, and
8) The quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The breadth of the claims, the nature of the invention, and relative skill level
The invention relates to a method of treating or preventing a viral infection comprising administering to a mammal a pharmaceutical composition of claim 40. In the absence of an explicit definition in Applicant’s specification, the claims are given their broadest reasonable interpretation. See MPEP 2111. Taber’s Cyclopedic Medical Dictionary (reference included with PTO-892) defines "prevention" as meaning, "The anticipation of harm, disease, or injury and the measures taken to block their effects." In order to block the effects of a condition, the preventative agent must be completely effective. Therefore, in order to give the broadest reasonable interpretation to the claims, “prevention” or "prevent" are thus interpreted to mean the complete blocking of all symptoms or effects of a disorder or condition for an indefinite period of time in all population types (gender, age, etc.).
The claim is broad insofar as it recites preventing any type of virus infection. As described above, preventing indicates that any type of virus infection must never occur by administering the claimed agents.
The relative skill of those in the art is high, that of an MD or PHD, someone with experience in viral infection.
The amount of direction or guidance provided and the presence or absence of working examples
Applicant demonstrates the antiviral activity of GCPQ (the compound as recited in instant claim 53) on Vero E6 and A549/ACE2+ cells infected with SARS-CoV-2 virus in Figure 2 (also see page 22 lines 35-37 through page 23- lines 1-5). Applicant shows that the presence of GCPQa and GCPQc at non-toxic concentrations significantly hamper SARS-CoV-2 replication in vitro. Applicant further demonstrates the antiviral activity of GCPQ in human airway epithelial (HAE) cells infected with SARS-CoV-2 virus in Figure 3 (also see page 23 lines 8-13) as well as in Figure 5, which demonstrates an in vitro viral inhibition of SARS-CoV-2 in both the respiratory tract swabs and brains of mice relative to controls (also see page 24 lines 5-20).
The described examples show that the claimed composition was effective in reducing the viral load of SARS-CoV-2 but does not show that SARS-CoV-2 was prevented. Furthermore, the disclosure and examples do not teach or suggest a method to predictably identify patients who would get a viral infection and then to further determine if the viral infection can be prevented by administering the claimed composition.
The state and predictability of the art
The state of the prior art discloses that there are uncertainties about how a subject comes in contact and is infected with a viral infection. For example, Galbadage et al. (in PTO-892) discloses there are differences in the propagation of COVID-19 among select nations. Galbadage et al. discloses that this raises questions on whether a full scientific understanding of disease transmission modes has yet to be attained, and thus whether there are more effective ways to prevent its spread (see page 1, second paragraph). Galabadage et al. discloses there are no current cures or vaccines for SARS-CoV-2 (see page 3 right column), and further illustrates in Figure 1 (page 2) the different potential modes of transmission of COVID-19. Additionally, McArthur et al. (in PTO-892) discloses that infectious diseases, which include viral infections, are unpredictable with the potential for global outbreaks (see page 298 first paragraph). McArthur et al. discloses that world travel and increased global interdependence have added to problems in diagnosing and containing these diseases. McArthur et al. discloses virus infections such as HIV/AIDS and H1N1 influenza as modern-day examples of the challenges of diagnosing and containing these infections (see paragraph first paragraph on page 298).
Therefore, due to uncertainties in how a viral infection such as SARS-CoV-2, HIV/AIDS, and H1N1 influenza spreads and thus incomplete information and difficulties to develop more effective methods to prevent transmission, the preventative application against a viral infection using the claimed composition is highly unpredictable in the arts.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of a predictable method to identify patients who would develop these diseases without treatment, no one skilled in the art would accept the assertion that the instantly claimed agents could be predictably used to prevent a viral infection as inferred by the claim and contemplated by the specification. Furthermore, the quantity of experimentation to develop a method that could be used to prevent viral infection would be undue because a method to predictably identify a patient who would get a virus infection does not exist and as described above, one of ordinary skill would have to develop this method such that the claimed method could then be used as a preventative measure against the viral infection. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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.
Claim(s) 40, 42, and 44-57 are rejected under 35 U.S.C. 103 as being unpatentable over Tanaka et al. (Viruses, 2013 in PTO-892) in view of Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023) and Uchegbu et al. (US20160279189A1 in IDS filed 05/13/2025).
Tanaka et al. discloses the suppression of coronavirus replication by cyclosporin A (CsA) (see Abstract). Tanaka et al. discloses that CsA inhibited the replication of coronaviruses (CoV) such as SARS-CoV and human 229E CoV as well as mouse hepatitis virus (MHV-A59) using green fluorescence protein (GFP)-expressing recombinant CoVs (see page 1252, last paragraph and Table 1 on page 1255). Tanaka et al. discloses that humans-cyclophilin A (CypA) is involved in the pathogenesis of viral infection and plays a critical role in the replication of viruses such as HIV-1, HCV, and other related viruses (see page 1251 third paragraph). Tanaka et al. discloses that CsA and other non-immunosuppressive compounds that bind to cellular cyclophilins such as IM811, Debio-025, and SCY-635 can inhibit HIV-1 and HCV replication (see page 1251 third paragraph).
The difference between Tanaka et al. and the claimed invention is that Tanaka et al. does not disclose a pharmaceutical composition comprising an amphiphilic carbohydrate compound as recited in claim 40.
Siew et al. discloses the enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles (GCPQ) (see Abstract). Siew et al. demonstrates that cyclosporin A formulated with GCPQ nanoparticles significantly enhanced the oral absorption of up to a 5-fold increase in comparison to cyclosporin A administered alone to Male Wistar Rats (see Abstract, page 17 right column, and Figure 5a on page 23). Siew et al. exemplifies a GCPQ-Cyclosporin A tablet formulation in Table 1 on page 17 that contained 5 mg/ml cyclosporin A, 100 mg/ml mannitol, 100 mg/ml avicel, 5 mg/ml stearic acid, 2 mg/ml sodium dodecyl sulfate, and 25 mg/ml GCPQ. Here, the tablet formulation meets the GCPQ compound having a concentration below 50% w/v recited in claim 56 (25 mg / mL GCPQ equates to 2.5% w/v of the tablet formulation). Siew et al. discloses two GCPQ compounds (GCPQ24 and GCPQ48) that were used in the formulations (see left column page 16). GCPQ24 had a MW of 12.195 kDA, mole% palmitoylation of 16%, and mole% quaternary ammonium groups of 8% (see left column page 16). Siew et al. discloses NMR data of their GCPQ compounds and identified several structures on the GCPQ such as [m, CH3−(CH2)12−CH2−CH2−CO−], [s, CH3−CO− NH−], [b, −CH−CH−NH−CH3− and −CH−CH−N(CH3)2], and [s −CH−CH−N(CH3)3] (see page 16 left column).
Uchegbu et al. discloses a composition comprising a hydrophilic drug and amphiphilic carbohydrate compound wherein the composition is intranasally administered to the human or animal body and for use in treating a variety of disorders and infective diseases (see Abstract). Uchegbu et al. discloses that their amphiphilic carbohydrate compound is represented by the formula shown in paragraph 0022 and shown below:
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392
1410
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The R and X groups are specified in paragraphs 0028-0033 and 0041-0046. Here, unit a corresponds to unit T when R8 and R9 are methyl and R10 is CH2CH2OH. Unit b corresponds to unit Q when R7 is absent, R1-3 are all methyl, and R4 is CH2CH2OH. Unit c corresponds to unit D when R5 is CH2CH2OH. Unit d corresponds to unit H when R6 is CH2CH2OH and X is CH3(CH2)nCO—NH—, where n is between 2 and 28. Uchegbu et al. discloses a+b+c+d=1 (paragraph 0023) and a is 0-0.970, b is 0.01-0.990, c is 0-0.970, and d is 0.01-0.990 (paragraphs 0024-0027). Uchegbu et al. discloses that the a, b, c and d units may be arranged in any order and may be ordered, partially ordered or random (see paragraph 0034). Uchegbu et al. discloses that the amphiphilic carbohydrate compound is preferably quaternary ammonium palmitoyl glycol chitosan (GCPQ) (paragraph 0052), which is the same GCPQ compound recited in claim 53. Uchegbu et al. demonstrates the intranasal administration of their GCPQ compound with Leucine5-enkephalin (LENK) in a rat CFA inflammatory pain model in Fig. 1 and in paragraphs 0082-0084). Uchegbu et al. discloses that the GCPQ had a MW of 22 kDA, a mole% palmitoylation of 13%, and a mole % quaternary ammonium group of 9.1% (paragraph 0083). Here, as disclosed in the specification, mole% palmitoylation corresponds to unit H and mole% quaternary ammonium group corresponds to unit Q (see page lines, 4-15 in specification). Uchegbu et al. discloses that the amphiphilic carbohydrate compound can form nanoparticles which can be loaded with hydrophilic drugs (see paragraph 0055).
It would have been prima facie obvious to combine Tanaka with Siew et al. and Uchegbu et al. before the effective filing date of the claimed invention by modifying the cyclosporin A compound disclosed in Tanaka into a GCPQ-Cyclosporin A tablet formulation as disclosed in Siew et al. and further optimizing the GCPQ compound of Siew based on the teachings of Uchegbu to arrive at the claimed invention. One of ordinary skill in the art would have been made these modifications with a reasonable expectation of success because Tanaka et al. establishes cyclosporin A can be used to treat various viral infection such as coronavirus, HIV-1, HCV, and several flaviviruses, and Siew et al. provides guidance of incorporating GCPQ nanoparticles to Cyclosporin A to improve the absorption of cyclosporin A of up to a 5-fold increase. Furthermore, Uchegbu et al. discloses similar GCPQ compounds as being useful for the same purpose of drug delivery as disclosed in Siew et al. and also provides guidance of a GCPQ compound with a structural formula that has the same D, H, Q, and T units with overlapping mole percentages and discloses that these units can be arranged in any order on the chitosan backbone. Therefore, an ordinary skilled artisan would be able to optimize the arrangement and the mole ratios of these units on the GCPQ compound such as disclosed in Siew and Uchegbu et al. to arrive at the recited amphiphilic carbohydrate compound of the instant claims.
Claim(s) 41 is rejected under 35 U.S.C. 103 as being unpatentable over Tanaka et al. (Viruses, 2013 in PTO-892) in view of Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023) and Uchegbu et al. (US20160279189A1 in IDS filed 05/13/2025)., as applied to claim 40, and further in view of JP’464 (JP2013199464A in PTO-892, an English translation is included and used as the basis of this rejection)
Tanaka et al. in view of Siew et al. and Uchegbu et al. teaches the method of claim 40 as described above.
The difference between the combination of Tanaka, Siew, and Uchegbu et al. and the claimed invention is that the combination of Tanaka, Siew, and Uchegbu et al. do not disclose wherein the composition is administered intranasally.
JP’464 discloses the use of cyclosporin A or a derivative therefore as an anti-influenza virus agent and treating influenza virus infections (see paragraph 0007). JP’464 discloses that the cyclosporin A can be prepared and administered in the form of nasal drops (see paragraphs 0016 and 0018).
It would have been prima facie obvious to combine Tanaka, Siew, and Uchegbu et al. with JP’464 before the effective filing date of the claimed invention by modifying the cyclosporin A – GCPQ composition as suggested by the combination of Tanaka, Siew, and Uchegbu et al. into a nasal formulation as disclosed in JP’464. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Uchegbu establishes intranasal administration of GCPQ based formulations, and JP’464 provides further guidance that cyclosporin A can be administered as a nasal drop for a virus infection. Therefore, an ordinary skilled artisan would have predictably considered preparing a nasal formulation of cyclosporin A – GCPQ for the same improved absorption effect.
Claim(s) 43 is rejected under 35 U.S.C. 103 as being unpatentable over Tanaka et al. (Viruses, 2013 in PTO-892) in view of Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023) and Uchegbu et al. (US20160279189A1 in IDS filed 05/13/2025), as applied to claim 40, and further in view of Soundararajan et al. (Dissertation, 2016 in PTO-892).
Tanaka et al. in view of Siew et al. and Uchegbu et al. teaches the method of claim 40.The difference between the combination of Tanaka, Siew, and Uchegbu et al. and the claimed invention is that the combination of Tanaka, Siew, and Uchegbu et al. do not disclose unit A in the range of 0.5-20 mole%.
Soundararajan et al. discloses the use of GCPQ compounds for enhancing the bioavailability of hydrophobic drugs by forming nanoparticles (see Abstract first paragraph on page 3). Soundararajan et al. provides an NMR spectra of GCPQ compounds in Figure 2.8 on page 78 with a chemical structure shown below:
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416
609
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Here, unit n corresponds to unit A when R1 is CH2CH2OH.
It would have been prima facie obvious to combine Tanaka, Siew, and Uchegbu et al. with Soundararajan et al. before the effective filing date of the claimed invention by further modifying the GCPQ compound as suggested by the combination of Tanaka, Siew, and Uchegbu described above to include the unit n of the GCPQ compound disclosed in Soundararajan et al. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Soundararajan et al. demonstrates GCPQ compounds contain this monomer unit and are useful the same purpose of improved drug delivery. Therefore, an ordinary skilled artisan would be able to include the same monomer unit and optimize the arrangement and mole ratios of the monomer units on GCPQ compounds such as disclosed in Siew and Uchegbu to arrive at the recited amphiphilic carbohydrate compound of the instant claims.
Claim(s) 58-59 are rejected under 35 U.S.C. 103 as being unpatentable over Tanaka et al. (Viruses, 2013 in PTO-892) in view of Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023) and Uchegbu et al. (US20160279189A1 in IDS filed 05/13/2025), as applied to claim 40, and further in view of Hijikata et al. (US20070275884A1 in PTO-892).
Tanaka et al. in view of Siew et al. and Uchegbu et al. teaches the method of claim 40.
The difference between the combination of Tanaka, Siew, and Uchegbu et al. and the claimed invention is that the combination of Tanaka, Siew, and Uchegbu et al. do not disclose wherein the composition is administered at a dose of 25 mg/kg to 100 mg/kg and that is administered once or twice a day.
Hijikata et al. discloses the use of cyclosporin for the treatment of Hepatitis C virus (HCV) (see Abstract and paragraph 0007). Hijikata et al. discloses that a preferred daily dosage of their cyclosporin compounds is in the range of about 1 to 50 mg/kg per day as a single dose or in divided doses (see paragraph 0093). Hijikata et al. discloses that daily dosages required in practicing their method will vary depending upon, for example, the non-immunosuppressive cyclophilin-binding cyclosporin employed, the host, the mode of administration, and the severity of the condition to be treated (see paragraph 0093).
It would have been prima facie obvious to combine Tanaka, Siew, and Uchegbu et al. with Hijikata et al. before the effective filing date of the claimed invention by optimizing the dosage of the cyclosporin A – GCPQ composition as suggested by the combination of Tanaka, Siew, and Uchegbu et al. with the cyclosporin dosage amounts disclosed in Hijikata et al. to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Hijikata et al. provides guidance that 1-50 mg/kg per day as a single dose or divided dose of a cyclosporin compound is effective for treating the same HCV as disclosed in Tanaka et al.
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 40 and 42-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 7,741,474 (‘474) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), and Soundararajan et al. (Dissertation, 2016 in PTO-892).
Claim 1 of ‘474 recites a solubilizing carbohydrate polymer of average molecular weight of about 2-30 kDa according the recited formula. Claim 2 of ‘474 recites the m, n, and p units form any arrangement in the solubilizing carbohydrate polymer. Claim 6 of ‘474 recites the carbohydrate polymer is selected from glycol chitosans. Claim 57 of ‘474 recites X is CH3(CH2)14CONH. Claim 8 of ‘474 recites the ratio of the carbohydrate polymer to a pharmaceutical acceptable carrier ranging from 0.05 wt% to 10 wt%. Claims 9-10 recites a pharmaceutical composition comprising the carbohydrate polymer and a drug such as cyclosporine.
The difference between the claims of ‘474 and the claimed invention is that the claims of ‘474 do not recite a method of treating a viral infection comprising an amphiphilic carbohydrate compound have the formula recited in instant claim 40.
The independent teachings of Tanaka, Siew, and Soundararajan are as described above.
It would have been prima facie obvious to combine the claims of ‘474 with Tanaka, Siew, and Soundararajan before the effective filing date of the claimed invention by using the composition comprising the carbohydrate polymer and cyclosporine as recited in the claims of ‘474 for the treatment of a viral infection as disclosed in Tanaka and formulating the composition of ‘474 into a tablet formulation as disclosed in Siew et al. as well as optimizing the amphiphilic carbohydrate polymer of ‘474 based on the teachings of Uchegbu and Soundararajan to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Tanaka et al. establishes cyclosporin A can be used to treat various viral infection such as coronavirus, HIV-1, HCV, and several flaviviruses, and Siew et al. provides guidance of incorporating GCPQ nanoparticles to Cyclosporin A for a tablet formulation to improve the absorption of cyclosporin A of up to a 5-fold increase. Furthermore, Uchegbu et al. discloses similar amphiphilic carbohydrate polymer compounds as being useful for the same purpose of drug delivery as disclosed in the claims of ‘474 and also provides guidance of a GCPQ compound with a structural formula that has the same D, H, Q, and T units with overlapping mole percentages and discloses that these units can be arranged in any order on the chitosan backbone. Lastly, Soundararajan et al. demonstrates that GCPQ compounds are known to contain the unit A monomer and are useful the same purpose of improved drug delivery. Therefore, an ordinary skilled artisan would be able to include the same monomer units and optimize the arrangement and mole ratios of these units on the polymer recited in the claims of ‘474 to arrive at the recited amphiphilic carbohydrate compound of the instant claims.
Claims 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 7,741,474 (‘474) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892), and JP’464 (JP2013199464A in PTO-892, an English translation is included and used as the basis of this rejection).The combination of the claims of ‘474 and the teachings of Tanaka, Siew et al., and Soundararajan recite the composition of instant claim 40 as described above.
However, this combination of the claims of ‘474 and the teachings of Tanaka, Siew et al., and Soundararajan do not recite a composition that is administered intranasally.
The teachings of JP’464 are described above.
It would have been prima facie obvious to combine the claims of ‘474, Tanaka, Siew et al., and Soundararajan with JP’464 before the effective filing date of the claimed invention by modifying the cyclosporin A – GCPQ composition as suggested by the combination of the claims of ‘474 and the teachings of Tanaka, Siew et al., and Soundararajan into a nasal formulation as disclosed in JP’464 et al. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Uchegbu establishes intranasal administration of GCPQ based formulations, and JP’464 provides further guidance that cyclosporin A can be administered as a nasal drop for a virus infection. Therefore, an ordinary skilled artisan would have predictably considered preparing a nasal formulation of cyclosporin A – GCPQ for the same improved absorption effect.
Claims 40 and 58-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 7,741,474 (‘474) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892), and Hijikata et al. (US20070275884A1 in PTO-892).
The combination of the claims of ‘474 and the teachings of Tanaka, Siew et al., and Soundararajan recite the composition of instant claim 40 as described above.
However, this combination of the claims of ‘474 and the teachings of Tanaka, Siew et al., and Soundararajan do not recite a composition that is administered at a dose of 25-100 mg/kg once or twice a day.
The teachings of Hijikata et al. are described above.
It would have been prima facie obvious to combine the claims of ‘474, Tanaka, Siew et al., and Soundararajan with Hijikata et al. before the effective filing date of the claimed invention by optimizing the dosage of the cyclosporin A – GCPQ composition as suggested by the combination of the claims of ‘474 and the teachings of Tanaka, Siew et al., and Soundararajan with the cyclosporin dosage amounts disclosed in Hijikata et al. to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Hijikata et al. provides guidance that 1-50 mg/kg per day as a single dose or divided dose of a cyclosporin compound is effective for treating the same HCV as disclosed in Tanaka et al.
Claims 40 and 42-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 8.470,371 (‘371) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892).
Claim 1 of ‘371 recites a polymeric micellar aggregate have a mean particle size between 20 nm and 500 nm formed from an amphiphilic carbohydrate polymer with the recited structural formula. Claim 10 of ‘371 recites wherein the hydrophobic group X is CH3(CH2)n—CO—, or CH3(CH2)n-, or CH3(CH2)p—CH═CH—(CH2)q—CO—NH—, or CH3(CH2)nCONH—, wherein n is between 4 and 30, and p and q may be the same or different and are between 3 and 15. Claim 20 of ‘371 recites wherein carbohydrate polymer has a molecular weight between about 1.5 kDa and about 250 kDa. Claims 24-26 of ‘371 recite wherein the polymeric micellar aggregate is formulated with a drug such as cyclosporine.
The difference between the claims of ‘371 and the claimed invention is that the claims of ‘371 do not recite a method of treating a viral infection comprising an amphiphilic carbohydrate compound have the formula recited in instant claim 40.
The independent teachings of Tanaka, Siew, and Soundararajan are as described above.
It would have been prima facie obvious to combine the claims of ‘371 with Tanaka, Siew, and Soundararajan before the effective filing date of the claimed invention by using the composition comprising the carbohydrate polymer and cyclosporine as recited in the claims of ‘371 for the treatment of a viral infection as disclosed in Tanaka and formulating the composition of ‘371 into a tablet formulation as disclosed in Siew et al. as well as optimizing the amphiphilic carbohydrate polymer of ‘371 based on the teachings of Uchegbu and Soundararajan to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Tanaka et al. establishes cyclosporin A can be used to treat various viral infection such as coronavirus, HIV-1, HCV, and several flaviviruses, and Siew et al. provides guidance of incorporating GCPQ nanoparticles to Cyclosporin A for a tablet formulation to improve the absorption of cyclosporin A of up to a 5-fold increase. Furthermore, Uchegbu et al. discloses similar amphiphilic carbohydrate polymer compounds as being useful for the same purpose of drug delivery as disclosed in the claims of ‘371 and also provides guidance of a GCPQ compound with a structural formula that has the same D, H, Q, and T units with overlapping mole percentages and discloses that these units can be arranged in any order on the chitosan backbone. Lastly, Soundararajan et al. demonstrates that GCPQ compounds are known to contain the unit A monomer and are useful the same purpose of improved drug delivery. Therefore, an ordinary skilled artisan would be able to include the same monomer units and optimize the arrangement and mole ratios of these units on the polymer recited in the claims of ‘371 to arrive at the recited amphiphilic carbohydrate compound of the instant claims.
Claims 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 8.470,371 (‘371) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892), and JP’464 (JP2013199464A in PTO-892, an English translation is included and used as the basis of this rejection).
The combination of the claims of ‘371 and the teachings of Tanaka, Siew, and Soundararajan recite the composition of instant claim 40 as described above.
However, this combination of the claims of ‘371 and the teachings of Tanaka, Siew, and Soundararajan do not recite a composition that is administered intranasally.
The teachings of JP’464 are described above.
It would have been prima facie obvious to combine the claims of ‘371, Tanaka, Siew, and Soundararajan with JP’464 before the effective filing date of the claimed invention by modifying the cyclosporin A – GCPQ composition as suggested by the combination of the claims of ‘371 and the teachings of Tanaka, Siew, and Soundararajan into a nasal formulation as disclosed in JP’464 et al. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Uchegbu establishes intranasal administration of GCPQ based formulations, and JP’464 provides further guidance that cyclosporin A can be administered as a nasal drop for a virus infection. Therefore, an ordinary skilled artisan would have predictably considered preparing a nasal formulation of cyclosporin A – GCPQ for the same improved absorption effect.
Claims 40 and 58-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 8.470,371 (‘371) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892), and Hijikata et al. (US20070275884A1 in PTO-892).
The combination of the claims of ‘371 and the teachings of Tanaka, Siew, and Soundararajan recite the composition of instant claim 40 as described above.
However, this combination of the claims of ‘371 and the teachings of Tanaka, Siew, and Soundararajan do not recite a composition that is administered at a dose of 25-100 mg/kg once or twice a day.
The teachings of Hijikata et al. are described above.
It would have been prima facie obvious to combine the claims of ‘371, Tanaka, Siew, and Soundararajan with Hijikata et al. before the effective filing date of the claimed invention by optimizing the dosage of the cyclosporin A – GCPQ composition as suggested by the combination of the claims of ‘371 and the teachings of Tanaka, Siew, and Soundararajan with the cyclosporin dosage amounts disclosed in Hijikata et al. to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Hijikata et al. provides guidance that 1-50 mg/kg per day as a single dose or divided dose of a cyclosporin compound is effective for treating the same HCV as disclosed in Tanaka et al.
Claims 40 and 42-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,987,304 (‘304) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), and Soundararajan et al. (Dissertation, 2016 in PTO-892).
Claim 7 of ‘304 recites a pharmaceutical composition that is a topical ocular formulation comprising one or more pharmaceutically acceptable excipients, a macrolide immunosuppressant drug selected from sirolimus, cyclosporine A, tacrolimus, and everolimus at a concentration of less than 2% w/v, and a quaternary ammonium palmitoyl glycol chitosan (GCPQ) at a concentration of less than 10% w/v, wherein the ratio of the concentration in w/v of GCPQ to the drug is greater than 5:1, and wherein GCPQ has a palmitoylation level between 10 mole % and 40 mole % and a quaternization level between 6 mole % and 20 mole %, wherein the formulation has a pH from 6.5 to 7.4.
The difference between the claims of ‘304 and the claimed invention is that the claims of ‘304 do not recite a method of treating a viral infection comprising an amphiphilic carbohydrate compound have the formula recited in instant claim 40.
The independent teachings of Tanaka, Siew, and Soundararajan are as described above.
It would have been prima facie obvious to combine the claims of ‘304 with Tanaka, Siew, and Soundararajan before the effective filing date of the claimed invention by using the composition comprising the carbohydrate polymer and cyclosporine as recited in the claims of ‘304 for the treatment of a viral infection as disclosed in Tanaka and formulating the composition of ‘304 into a tablet formulation as disclosed in Siew et al. as well as optimizing the amphiphilic carbohydrate polymer of ‘304 based on the teachings of Uchegbu and Soundararajan to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Tanaka et al. establishes cyclosporin A can be used to treat various viral infection such as coronavirus, HIV-1, HCV, and several flaviviruses, and Siew et al. provides guidance of incorporating GCPQ nanoparticles to Cyclosporin A for a tablet formulation to improve the absorption of cyclosporin A of up to a 5-fold increase. Furthermore, Uchegbu et al. discloses similar amphiphilic carbohydrate polymer compounds as being useful for the same purpose of drug delivery as disclosed in the claims of ‘304 and also provides guidance of a GCPQ compound with a structural formula that has the same D, H, Q, and T units with overlapping mole percentages and discloses that these units can be arranged in any order on the chitosan backbone. Lastly, Soundararajan et al. demonstrates that GCPQ compounds are known to contain the unit A monomer and are useful the same purpose of improved drug delivery. Therefore, an ordinary skilled artisan would be able to include the same monomer units and optimize the arrangement and mole ratios of these units on the polymer recited in the claims of ‘304 to arrive at the recited amphiphilic carbohydrate compound of the instant claims.
Claims 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,987,304 (‘304) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892), and JP’464 (JP2013199464A in PTO-892, an English translation is included and used as the basis of this rejection).
The combination of the claims of ‘304 and the teachings of Tanaka, Siew, and Soundararajan recite the composition of instant claim 40 as described above.
However, this combination of the claims of ‘304 and the teachings of Tanaka, Siew, and Soundararajan do not recite a composition that is administered intranasally.
The teachings of JP’464 are described above.
It would have been prima facie obvious to combine the claims of ‘304, Tanaka, Siew, and Soundararajan with JP’464 before the effective filing date of the claimed invention by modifying the cyclosporin A – GCPQ composition as suggested by the combination of the claims of ‘304 and the teachings of Tanaka, Siew, and Soundararajan into a nasal formulation as disclosed in JP’464 et al. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Uchegbu establishes intranasal administration of GCPQ based formulations, and JP’464 provides further guidance that cyclosporin A can be administered as a nasal drop for a virus infection. Therefore, an ordinary skilled artisan would have predictably considered preparing a nasal formulation of cyclosporin A – GCPQ for the same improved absorption effect.
Claims 40 and 58-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,987,304 (‘304) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), Soundararajan et al. (Dissertation, 2016 in PTO-892), and Hijikata et al. (US20070275884A1 in PTO-892).
The combination of the claims of ‘304 and the teachings of Tanaka, Siew, and Soundararajan recite the composition of instant claim 40 as described above.
However, this combination of the claims of ‘304 and the teachings of Tanaka, Siew, and Soundararajan do not recite a composition that is administered at a dose of 25-100 mg/kg once or twice a day.
The teachings of Hijikata et al. are described above.
It would have been prima facie obvious to combine the claims of ‘304, Tanaka, Siew, and Soundararajan with Hijikata et al. before the effective filing date of the claimed invention by optimizing the dosage of the cyclosporin A – GCPQ composition as suggested by the combination of the claims of ‘304 and the teachings of Tanaka, Siew, and Soundararajan with the cyclosporin dosage amounts disclosed in Hijikata et al. to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Hijikata et al. provides guidance that 1-50 mg/kg per day as a single dose or divided dose of a cyclosporin compound is effective for treating the same HCV as disclosed in Tanaka et al.
Claims 40 and 42-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 17/926,772 (‘772) in view of Tanaka et al. (Viruses, 2013 in PTO-892), Siew et al. (Molecular Pharmaceutics, 2012 in IDS filed on 02/28/2023), and Soundararajan et al. (Dissertation, 2016 in PTO-892).
Claim 1 of ‘772 recites an amphiphilic carbohydrate compound of average molecular weight 1-50 kDa with the recited structural formula. Claim 3 of ‘772 recites a species of the compound recited in claim 1 of ‘772. Claim 9 of ‘772 recites the amphiphilic compound is a partially acetylated form of GCPQ. Claim 11-13 and 15 of ‘772 recites a pharmaceutical composition comprising the amphiphilic carbohydrate compound and a hydrophobic drug such as cyclosporin A.
The difference between the claims of ‘772 and the claimed invention is that the claims of ‘772 do not recite a method of treating a viral infection comprising an amphiphilic carbohydrate compound have the formula recited in instant claim 40.
The independent teachings of Tanaka, Siew, and Soundararajan are as described above.
It would have been prima facie obvious to combine the claims of ‘772 with Tanaka, Siew, and Soundararajan before the effective filing date of the claimed invention by using the composition comprising the carbohydrate polymer and cyclosporine as recited in the claims of ‘772 for the treatment of a viral infection as disclosed in Tanaka and formulating the composition of ‘772 into a tablet formulation as disclosed in Siew et al. as well as optimizing the amphiphilic carbohydrate polymer of ‘772 based on the teachings of Uchegbu and Soundararajan to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Tanaka et al. establishes cyclosporin A can be used to treat various viral infection such as coronavirus, HIV-1, HCV, and several flaviviruses, and Siew et al. provides guidance of incorporating GCPQ nanoparticles to Cyclosporin A for a tablet formulation to improve the absorption of cyclosporin A of up to a 5-fold increase. Furthermore, Uchegbu et al. discloses similar amphiphilic carbohydrate polymer compounds as being useful for the same purpose of drug delivery as disclosed in the claims of ‘772 and also provides guidance of a GCPQ compound with a structural formula that has the same D, H, Q, and T units with overlapping mole percentages and discloses that these units can be arranged in any order on the chitosan backbone. Lastly, Soundararajan et al. demonstrates that GCPQ