DETAILED ACTION
Claims 1-16,18, and 19 are pending in the instant application and being examined on the merit.
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 .
Information Disclosure Statement
Applicant’s IDS submitted 3/3/2023 and IDS submitted 5/23/2022 have been acknowledged and considered. Signed copies are attached hereto.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. The references that have been cited by the Applicant in the specification but not listed in the IDS are listed below:
LeMahieu (1974) (Page 19, line 15)
Remington’s Pharmaceutical Sciences 18 Ed. or later (Page 21, lines 6-7)
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show “heavy black arrows pointing upward” (Page 3, lines 28-29) as described in the specification in regards to FIG 1. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
In addition to Replacement Sheets containing the corrected drawing figure(s), applicant is required to submit a marked-up copy of each Replacement Sheet including annotations indicating the changes made to the previous version. The marked-up copy must be clearly labeled as “Annotated Sheets” and must be presented in the amendment or remarks section that explains the change(s) to the drawings. See 37 CFR 1.121(d)(1). Failure to timely submit the proposed drawing and marked-up copy will result in the abandonment of the application.
Specification
The disclosure is objected to because of the following informalities:
“and (IgA+ASCs),” should read “and IgA+ASCs),” (Page 3, line 29)
“micronutrients” should read “micronutrient” (Page 5, line 7)
“form-lations” should read “formulations” (Page 20, lines 1-2)
“the at least” should read “at least” (Page 20, line 14)
Appropriate correction is required.
The use of the term Invivogen, Nutrisoy, Gemini, Phenomenex, Invitrogen, Icosagen, RNALater, TRIzol, IsoCage, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. All trademarks referenced herein should be identified as such with the appropriate notation:
Invivogen (Page 42, line 14)
Nutrisoy (Table on Page 45, line 9)
Gemini (Page 46, line 15)
Phenomenex (Page 46, line 15)
Invitrogen (Page 48, line 3)
Icosagen (Page 48, line 4)
RNALater (Page 48, line 17)
TRIzol (Page 48, line 17)
IsoCage (Page 49, line 6)
Claim Objections
Claim 13 is objected to because of the following informalities:
In claim 13, “patent” should read “patient”.
Appropriate correction is required.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 6-11, 13-14, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Hutchins et al (US Patent No. 2021/0283242 A1, priority to 3/2/2020), Li et al (Aging, 2020, 12(15):15784-15796), Surman et al (Vaccine, 2014, 32:2521-2524), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9).
Regarding instant claims 1-2, 6-7, 9-11, 13-4, and 18-19, Hutchins et al teaches a method wherein subjects were administered an effective pharmaceutical composition of a gp96-Ig-S vaccine with a pharmaceutically acceptable excipient which primed a strong effector memory CD8+ T-cell response (page 38, paragraph [0326]), wherein protein S (SARS-CoV-2 coronavirus spike protein) specific CD8 and CD4 Th1 T Cell responses were both induced by the gp96-Ig-S vaccine (page 38, paragraph [0327]; FIG. 4A-B and FIG. 6A-D), wherein the vaccine was comprised of gp96 fused to an immunoglobulin domain, which acted as a potent adjuvant that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to create a potent vaccine, designed to generate protective, adaptive and humoral immunity against shared sequences of SARS-CoV-2 (page 37, paragraph [0321]). Hutchins et al also discloses that administration of the vaccine can be through any route considered appropriate by a medical practitioner, including, for example, intranasal administration (page 33, paragraph [0273]). Furthermore, Hutchins et al provides a description of a kit that comprises the gp96-Ig-S vaccine system in accordance with embodiments of the disclosure (page 5, paragraph [0049]).
Hutchins et al, however, does not directly teach orally administering vitamin A to the patient, wherein the vitamin A is administered at least once within three days before or after the administration of the vaccine composition.
This deficiency is resolved by Li et al, Surman et al, and Penkert et al.
Penkert et al teaches that vitamin A (VA) is a retinoid molecule (page 2, paragraph 2), and, in regards to instant claim 8, when VAs are administered either orally or intranasally, they can correct responses when given at the time of vaccination (page 2, paragraph 7).
Furthermore, Li et al teaches that VA has anti-inflammatory properties and demonstrates several pharmacological mechanisms against SARS-CoV, namely, cytoprotective action, anti-viral activity, anti-inflammatory effects, and immunity-based immunomodulation (page 15790, paragraph 1).
Finally, Surman et al teaches that oral administration of vitamin A to Vitamin A-deficient (VAD) mice in the form of retinoic acid, or the more clinically preferred form retinyl palmitate, administered at days 0, 3, and 7 relative to the FluMist vaccination, improved the URT d-NALT IgA-producing AFCs (responsible for IgA production at the mucosal surface), exhibiting levels typical of control, healthy animals (page 2523, paragraphs 1&2; Fig. 2).
Regarding instant claims 1-2 and 6-8, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the effective coronavirus vaccination method of Hutchins et al of administering an effective pharmaceutical composition of the gp96-Ig-S vaccine with a pharmaceutically acceptable excipient, wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2 and modify the method to include oral co-administration of vitamin A as taught by Penkert et al. This is obvious, because Hutchins et al teaches a method comprising the gp96-Ig-S vaccine with embodiments described in the disclosure (e.g. a pharmaceutically acceptable excipient), wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, Li et al teaches vitamin A is effective against SARS-CoV-2, and Surman et al teaches that vitamin A administration at days 0, 3 and 7 relative to vaccination improved response to the vaccine. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to orally co-administer vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al at days 0, 3, or 7 relative to vaccination as taught by Surman et al with the gp96-Ig-S vaccine of Hutchins et al to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and further orally administering vitamin A at least once within three days before, or after the administration of the first composition.
Regarding instant claims 9-11, 13-14, 18 and 19, it would have been obvious for a person having ordinary skill in the art at the time of filing to put the composition comprising the gp96-Ig-S vaccine with a pharmaceutically acceptable excipient and vitamin A that is administered in the combined methods of Hutchins et al, Penkert et al, and Li et al in a vaccination kit or dosage regimen, because Hutchins et al teaches a vaccination kit comprising the gp96-Ig-S vaccine with embodiments described in the disclosure (e.g. a pharmaceutically acceptable excipient), wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, and Li et al teaches that vitamin A is effective against SARS-CoV-2. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to orally co-administer vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al with the gp96-Ig-S vaccine kit of Hutchins et al to form the instant kit or dosage regimen to vaccinate a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and further orally administering vitamin A.
Claims 4, 5, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hutchins et al (US Patent No. 2021/0283242 A1, priority to 3/2/2020), Li et al (Aging, 2020, 12(15):15784-15796), Surman et al (Vaccine, 2014, 32:2521-2524), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9), as applied to claim 1 above, and further in view of Patel et al (Viruses, 2019, 11(907):1-21, IDS entered on 03/03/2023) and Xu et al (J Transl Med, 2020, 18(322):1-12).
The teachings of Hutchins et al, Li et al, Surman et al and Penkert et al are discussed above. However, Hutchins et al, Li et al, Surman et al and Penkert et al do not teach orally administering vitamin D to the patient before, at the same time, or within 3 days from the administration of the vaccine composition or in the period between one week before and two days after the administration of the vaccine composition.
The deficiency is resolved by Patel et al and Xu et al.
Patel et al teaches that vitamin A and D supplementation could improve immune responses to vaccines when administered in combination (page 5, section 3.2; Table 2; and Figure 1) at the time of vaccination (Day 0) (page 5, section 3.1).
Additionally, Xu et al teaches that vitamin D potentially aids in preventing and treating SARS-CoV-2 infection by immunomodulatory functions in both innate and adaptive immunity (page 4, paragraph 2; and FIG. 2). Xu et al further teaches that vitamin D is known to exert direct antibacterial and antiviral actions (page 4, paragraph 3), and due to its immunomodulatory functions, Xu highlights that there are several ongoing vitamin D clinical trials for COVID-19 (Table S1).
Regarding instant claims 4 and 5, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the method of vaccinating patients comprised of administering the gp96-Ig-S vaccine and vitamin A of combined teachings of Hutchins et al, Penkert et al, Surman et al and Li et al to include orally administering vitamin D as taught by Patel et al. This is obvious, because Hutchins et al teaches administering the gp96-Ig-S vaccine with embodiments described in the disclosure (e.g. a pharmaceutically acceptable excipient), wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, Li et al teaches vitamin A is effective against SARS-CoV-2, and Surman et al teaches that vitamin A administration at days 0, 3 and 7 relative to vaccination improved response to the vaccine.
Furthermore, Patel et al teaches the prophylactic strategy of associating the use of vaccines with vitamins A and D supplementation at the time of vaccination to improve immune responses to vaccines, and Xu et al teaches vitamin D is effective against SARS-CoV-2 (COVID-19) due to its immunomodulatory functions. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to include orally co-administering vitamin D (shown to be effective against SARS-CoV-2 as taught by Xu et al) at the time of vaccination as taught by Patel et al with the gp96-Ig-S vaccine that comprises the spike protein (S) of SARS-CoV-2 and vitamin A in the combined teachings of Hutchins et al, Penkert et al, Surman et al, and Li et al to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamins A (within three days before or after the administration of the first composition) and D (before, at the same time, or within 3 days from the administration of the vaccine composition or in the period between one week before and two days after the administration of the vaccine composition).
Regarding claim 16, it would have been obvious for a person having ordinary skill in the art at the time of filing to put the composition comprising gp96-Ig-S vaccine with a pharmaceutically acceptable excipient and vitamins A and D that is administered in the combined methods of Hutchins et al, Penkert et al, Li et al, Patel et al, and Xu et al in a dosage regimen, because Hutchins et al teaches administering the gp96-Ig-S vaccine with embodiments described in the disclosure (e.g. a pharmaceutically acceptable excipient), wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, and Li et al teaches vitamin A is effective against SARS-CoV-2. Furthermore, Patel et al teaches the prophylactic strategy of associating the use of vaccines with vitamins A and D supplementation at the time of vaccination to improve immune responses to vaccines, and Xu et al teaches vitamin D is effective against SARS-CoV-2 (COVID-19) due to its immunomodulatory functions. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to include orally co-administering vitamin D (shown to be effective against SARS-CoV-2 as taught by Xu et al) at the time of vaccination as taught by Patel et al with the gp96-Ig-S vaccine that comprises the spike protein (S) of SARS-CoV-2 and vitamin A in the combined teachings of Hutchins et al, Penkert et al, and Li et al to form the instant dosage regimen to vaccinate a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamins A and D.
Double patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 6-15, 18, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-16 and 18 of U.S. Patent No. 10,919,927 B2 (hereinafter Patent ‘927, IDS entered on 03/03/2023) in view of Hutchins et al (US Patent No. 2021/0283242 A1), Li et al (Aging, 2020, 12(15):15784-15796), Surman et al (Vaccine, 2014, 32:2521-2524), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9).
Claims 1, 11, and 12 of Patent ‘927 teach a compound, Formula (I), comprising the chemical structure shown below:
PNG
media_image1.png
186
227
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.
Formula (I) of Patent ‘927 is identical to the structure of instant Formula (I) disclosed in the instant application. Claims 2-3, 10, and 13-14 of Patent ‘927 further teach a pharmaceutical composition comprising Formula (I) and one or more pharmaceutically accepted excipients, wherein the pharmaceutical composition is formulated for various administration routes, including mucosal administration or administration by inhalation. Claims 4, 9, 15-16, and 18 of Patent ‘927 also disclose a method of treating a viral infection (e.g. an infection caused by a coronavirus), the method comprising administering to a human in need thereof a therapeutically effective amount of Formula (I).
Patent ‘927, however, does not explicitly teach using Formula (I) and a pharmaceutically acceptable excipient in combination with an antigen and oral vitamin A to treat viral infections (e.g. viral infections caused by coronavirus).
The deficiency is resolved by Hutchins et al, Li et al, Surman et al, and Penkert et al.
As described in the 103 rejections above, the teachings of Hutchins et al, Penkert et al, Surman et al and Li et al are described above.
Regarding instant claims 1-3 and 6-8, it would have been obvious for a person having ordinary skill in the art to add an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 as taught by Hutchins et al to the method disclosed in Patent ‘927 of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by mucosal or inhalation routes, and further include oral co-administration of vitamin A as taught by Penkert et al. This is obvious, because Patent ‘927 teaches a method of treating viral infections comprising of a TLR2 agonist comprising Formula (I) and a pharmaceutical composition comprising formula (I) that is formulated for administration by inhalation, Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, Li et al teaches vitamin A is effective against SARS-CoV-2, and Surman et al teaches that vitamin A administration at days 0, 3 and 7 relative to vaccination improved response to the vaccine. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to add the antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 taught by Hutchins et al to the pharmaceutical composition comprising TLR2 agonist Formula (I) and a pharmaceutically accepted excipient disclosed in Patent ‘927 and further orally co-administer vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al at days 0, 3, or 7 relative to vaccination as taught by Surman et al to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of a first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamin A within three days before or after the administration of the first composition.
Regarding instant claims 9-11, 13-14, 18 and 19, it would have been obvious for a person having ordinary skill in the art at the time of filing to add an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to the method of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by mucosal or inhalation routes, and further include oral co-administration of vitamin A as taught in the combined methods of Patent ‘927, Hutchins et al, Penkert et al, and Li et al in a vaccination kit or a dosage regimen. This is obvious, because Patent ‘927 teaches a method of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by mucosal or inhalation routes, Hutchins et al teaches a vaccination kit comprising the gp96-Ig-S vaccine with embodiments described in the disclosure (e.g. a pharmaceutically acceptable excipient), wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, and Li et al teaches vitamin A is effective against SARS-CoV-2. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to orally co-administer vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al with the gp96-Ig-S vaccine of Hutchins et al to form the instant kit and dosage regimen to vaccinate a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and further orally administering vitamin A.
Claims 4, 5, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-16 and 18 of U.S. Patent No. 10,919,927 B2 (hereinafter Patent ‘927) in view of Hutchins et al (US Patent No. 2021/0283242 A1), Li et al (Aging, 2020, 12(15):15784-15796), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9), as applied to claim 1 above, and in further view of Patel et al (Viruses, 2019, 11(907):1-21, IDS entered on 03/03/2023) and Xu et al (J Transl Med, 2020, 18(322):1-12).
The teachings of Patent ‘927 in view of Hutchins et al, Li et al, Surman et al, and Penkert et al are in the NSDP rejection above.
Patent ‘927, Hutchins et al, Li et al, Surman et al, and Penkert et al do not teach orally administering vitamin D to the patient before, at the same time, or within 3 days from the administration of the vaccine composition or in the period between one week before and two days after the administration of the vaccine composition.
The deficiency is resolved by Patel et al and Xu et al.
As described in the 103 rejections above, the teachings of Patel et al and Xu et al are described above.
Regarding instant claims 4 and 5, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the method according to claim 1 comprising adding an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to the method of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by mucosal or inhalation routes, and oral co-administration of vitamin A as taught in the combined methods of Patent ‘927, Hutchins et al, Penkert et al, Surman et al, and Li et al and modify it to further comprise orally administering vitamin D as taught by Patel et al. This is obvious, because Patent ‘927 teaches a method of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by inhalation, Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, Li et al teaches vitamin A is effective against SARS-CoV-2, and Surman et al teaches that vitamin A administration at days 0, 3 and 7 relative to vaccination improved response to the vaccine. Furthermore, Patel et al teaches the prophylactic strategy of associating the use of vaccines with vitamins A and D supplementation at the time of vaccination to improve immune responses to vaccines, and Xu et al teaches vitamin D is effective against SARS-CoV-2 (COVID-19) due to its immunomodulatory functions. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to further orally co-administer vitamin D (shown to be effective against SARS-CoV-2 as taught by Xu et al) as taught by Patel et al with vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al at days 0, 3, or 7 relative to vaccination as taught by Surman et al to the vaccine method comprising the antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 taught by Hutchins et al and the pharmaceutical composition comprising Formula (I) and a pharmaceutically accepted excipient taught by Patent ‘927 to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamins A (within three days before or after the administration of the first composition) and D (before, at the same time, or within 3 days from the administration of the vaccine composition or in the period between one week before and two days after the administration of the vaccine composition).
Regarding instant claim 16, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the method according to claim 1 comprising adding an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to the method of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by inhalation, and oral co-administration of vitamin A as taught in the combined methods of Patent ‘927, Hutchins et al, Penkert et al, and Li et al and modify it to further comprise orally administering vitamin D as taught by Patel et al in a dosage regimen. This is obvious, because Patent ‘927 teaches a method of treating viral infections comprising of a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered by mucosal or inhalation routes, Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, and Li et al teaches vitamin A is effective against SARS-CoV-2. Furthermore, Patel et al teaches the prophylactic strategy of associating the use of vaccines with vitamins A and D supplementation at the time of vaccination to improve immune responses to vaccines, and Xu et al teaches vitamin D is effective against SARS-CoV-2 (COVID-19) due to its immunomodulatory functions. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to include orally co-administering vitamin D (shown to be effective against SARS-CoV-2 as taught by Xu et al) at the time of vaccination as taught by Patel et al with vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al and the vaccine method comprising the antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 taught by Hutchins et al and the pharmaceutical composition comprising Formula (I) and a pharmaceutically accepted excipient taught by Patent ‘927 to form the instant dosage regimen to vaccinate a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamins A and D.
Claims 1-3, 6-15, 18, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, and 9 of U.S. Patent No. 11,059,846 B2 (hereinafter Patent ‘846) in view of Hutchins et al (US Patent No. 2021/0283242 A1), Li et al (Aging, 2020, 12(15):15784-15796), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9).
Claim 1 of Patent ‘846 teaches a compound, Formula (I), comprising the chemical structure shown below:
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Formula (I) of Patent ‘846 is identical as the chemical structure of instant Formula (I) of the instant application. Claims 2 and 3 of Patent ‘846 further teach a pharmaceutical composition comprising Formula (I) and one or more pharmaceutically accepted excipients for use in medicine and treatment of intracellular infections. Furthermore, claims 4 and 9 of Patent ‘846 also disclose a method comprising administering to a human in need thereof a therapeutically effective amount of Formula (I) and a pharmaceutically accepted excipient. Finally, the specification describes that the composition can be administered by any conventional administration route, such as any parenteral route, which includes pulmonary administration (page 21, section 7, paragraph 4).
Patent ‘846, however, does not explicitly teach using Formula (I) and a pharmaceutically acceptable excipient in combination with an antigen and oral vitamin A to treat viral infections, such as those caused by coronaviruses.
The deficiency is resolved by Hutchins et al, Li et al, Surman et al, and Penkert et al.
As described in the 103 rejections above, the teachings of Hutchins et al, Penkert et al, Surman et al, and Li et al are described above.
Regarding instant claims 1-3 and 6-8, it would have been obvious for a person having ordinary skill in the art to add an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 as taught by Hutchins et al to the method disclosed in Patent ‘846 comprising a TLR2 agonist comprising Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, and further include oral co-administration of vitamin A as taught by Penkert et al. This is obvious, because Patent ‘846 teaches a method comprising a TLR2 agonist (specification page 26, section 18, Example 4; and Table 2) comprising Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, Li et al teaches vitamin A is effective against SARS-CoV-2, and Surman et al teaches that vitamin A administration at days 0, 3 and 7 relative to vaccination improved response to the vaccine. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to add the antigen comprising spike proteins from SARS-CoV-2 taught by Hutchins et al to the pharmaceutical composition comprising Formula (I) and a pharmaceutically accepted excipient disclosed in Patent ‘846 and further orally co-administer vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al at days 0, 3, or 7 relative to vaccination as taught by Surman et al to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of a first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamin A within three days before or after the administration of the first composition.
Regarding instant claims 9-11, 13-14, 18 and 19, it would have been obvious for a person having ordinary skill in the art at the time of filing to add an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to the method comprising of a TLR2 agonist comprising Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, and further include oral co-administration of vitamin A as taught in the combined methods of Patent ‘846, Hutchins et al, Penkert et al, and Li et al in a vaccination kit or dosage regimen. This is obvious, because Patent ‘846 teaches a method comprising a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, Hutchins et al teaches a vaccination kit comprising the gp96-Ig-S vaccine with embodiments described in the disclosure (e.g. a pharmaceutically acceptable excipient), wherein gp96-Ig-S is comprised of gp96 fused to an immunoglobulin domain that activated TLR2 and the coronavirus spike proteins S1 and S2 of SARS-CoV-2, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, and Li et al teaches vitamin A is effective against SARS-CoV-2. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to add the antigen comprising spike proteins from SARS-CoV-2 taught by Hutchins et al to the pharmaceutical composition comprising Formula (I) and a pharmaceutically accepted excipient disclosed in Patent ‘846 and further orally co-administer vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al to form the instant kit and dosage regimen to vaccinate a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of a first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamin A.
Claims 4, 5, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, and 9 of U.S. Patent No. 11,059,846 B2 (hereinafter Patent ‘846) in view of Hutchins et al (US Patent No. 2021/0283242 A1), Li et al (Aging, 2020, 12(15):15784-15796), Surman et al (Vaccine, 2014, 32:2521-2524), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9), as applied to claim 1 above, and in further view of Patel et al (Viruses, 2019, 11(907):1-21, IDS entered on 03/03/2023) and Xu et al (J Transl Med, 2020, 18(322):1-12).
The teachings of ‘846 in view of Hutchins et al, Li et al, Surman et al, and Penkert et al are in the NSDP rejection above.
However, Patent ‘846, Hutchins et al, Li et al, Surman et al, and Penkert et al do not teach orally administering vitamin D to the patient before, at the same time, or within 3 days from the administration of the vaccine composition or in the period between one week before and two days after the administration of the vaccine composition.
The deficiency is resolved by Patel et al and Xu et al.
As described in the 103 rejections above, the teachings of Patel et al and Xu et al are described above.
Regarding instant claims 4 and 5, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the method according to claim 1 comprising adding an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to the method comprising a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, and include oral co-administration of vitamin A as taught in the combined methods of Patent ‘846, Hutchins et al, Penkert et al, Surman et al, and Li et al and modify it to further comprise orally administering vitamin D as taught by Patel et al. This is obvious, because Patent ‘846 teaches a method comprising a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, Li et al teaches vitamin A is effective against SARS-CoV-2, and Surman et al teaches that vitamin A administration at days 0, 3 and 7 relative to vaccination improved response to the vaccine. Furthermore, Patel et al teaches the prophylactic strategy of associating the use of vaccines with vitamins A and D supplementation at the time of vaccination to improve immune responses to vaccines, and Xu et al teaches that vitamin D is effective against SARS-CoV-2 (COVID-19) due to its immunomodulatory functions. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to further orally co-administer vitamin D (shown to be effective against SARS-CoV-2 as taught by Xu et al) as taught by Patel et al at the time of vaccination with vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al at days 0, 3, or 7 relative to vaccination as taught by Surman et al to the vaccine method comprising the antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 taught by Hutchins et al and the pharmaceutical composition comprising Formula (I) and a pharmaceutically accepted excipient taught by Patent ‘846 to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamins A (within three days before or after the administration of the first composition) and D (before, at the same time, or within 3 days from the administration of the vaccine composition or in the period between one week before and two days after the administration of the vaccine composition).
Regarding instant claim 16, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the method according to claim 1 comprising adding an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 to the method comprising a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, and include oral co-administration of vitamin A as taught in the combined methods of Patent ‘846, Hutchins et al, Penkert et al, and Li et al and modify it to further comprise orally administering vitamin D as taught by Patel et al in a dosage regimen. This is obvious, because Patent ‘846 teaches a method comprising a TLR2 agonist Formula (I) and a pharmaceutically acceptable excipient, which can be administered parenterally, Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory infection vaccine is effective, and Li et al teaches vitamin A is effective against SARS-CoV-2. Furthermore, Patel et al teaches the prophylactic strategy of associating the use of vaccines with vitamins A and D supplementation at the time of vaccination to improve immune responses to vaccines, and Xu et al teaches that vitamin D is effective against SARS-CoV-2 (COVID-19) due to its immunomodulatory functions. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to include orally co-administering vitamin D (shown to be effective against SARS-CoV-2 as taught by Xu et al) at the time of vaccination as taught by Patel et al with vitamin A (shown to be effective against SARS-CoV-2 as taught by Li et al) as taught by Penkert et al and the vaccine method comprising the antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 taught by Hutchins et al and the pharmaceutical composition comprising Formula (I) and a pharmaceutically accepted excipient taught by Patent ‘846 to form the instant method of vaccinating a patient in need thereof against respiratory viruses comprising pulmonal or intranasal administration of first composition comprising an antigen, a TLR2 agonist (e.g. instant Formula (I)), and a pharmaceutically acceptable excipient and oral administration of vitamins A and D.
Claims 1-3, 6-15, 18, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 14, and 15 of U.S. Patent No. 11,059,845 B2 (hereinafter Patent ‘845) in view of Hutchins et al (US Patent No. 2021/0283242 A1), Li et al (Aging, 2020, 12(15):15784-15796), Surman et al (Vaccine, 2014, 32:2521-2524), and Penkert et al (Front. Immunol., 2019, 10(1576):1-9). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1-12 of Patent ‘845 teaches compound I comprising the following chemical structure (Figure 1):
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Compound 1 as disclosed in Patent ‘845 is the same chemical compound disclosed in instant application as instant Formula (I). Claims 14 and 15 of Patent ‘845 teaches a pharmaceutical composition comprising compound 1 and a method for treating an intracellular infection with a therapeutically effective amount of the compound.
Patent ‘845, however, does not explicitly teach using compound 1 and a pharmaceutically acceptable excipient in combination with an antigen and oral vitamin A to treat viral infections.
The deficiency is resolved by Hutchins et al, Li et al, Surman et al, and Penkert et al.
As described in the 103 rejections above, the teachings of Hutchins et al, Penkert et al, Surman et al, and Li et al are described above.
Regarding instant claims 1-3 and 6-8, it would have been obvious for a person having ordinary skill in the art to add an antigen comprising the coronavirus spike proteins S1 and S2 of SARS-CoV-2 as taught by Hutchins et al to the method disclosed in Patent ‘845 comprising a TLR2 agonist comprising compound 1 and a pharmaceutically acceptable excipient, which can be administered nasally, and further include oral co-administration of vitamin A as taught by Penkert et al. This is obvious, because Patent ‘845 teaches a method comprising compound 1 and a pharmaceutically acceptable excipient, wherein compound 1 stimulates TLR2 (page 37, section 40, Example 17), may be used as immune modulating adjuvants in vaccination (page 18, section 1, paragraph 1) for the treatment of viral infections, such as coronavirus infections (page 25, section 15, paragraph 4), can be used together with one or more pharmaceutically acceptable excipients (Page 25, section 16, paragraph 3), and the pharmaceutical composition comprising compound 1 may be administered through any conventional routes, including nasal administration (page 25, section 16, paragraph 4). Hutchins et al teaches coadministration with an antigen (e.g. spike proteins of SARS-CoV-2) is critical to induce an immune response, Penkert et al teaches oral co-administration of vitamin A with a respiratory