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 .
Claims 1, 2 and 4-20 are pending and are examined on the merits.
Information Disclosure Statement
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.
Response to Amendment
The declaration under 37 CFR 1.130(a) filed on 5/7/26 is sufficient to overcome the rejection of claims 1-20 based on 35 USC 102a as being anticipated by Renu et al. (Frontiers in Immunology, 2021, Vol. 12, pages 1-13). The Renu et al. publications is applicant’s own work and published within a year of the earliest effective priority date.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Withdrawn rejection in view of amendments) Claims 14 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(Withdrawn rejection in view of declaration) Claim(s) 1-20 are rejected under 35 U.S.C. 102a1 as being anticipated by Renu et al. (Frontiers in Immunology, 2021, Vol. 12, pages 1-13).
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.
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.
(Prior Rejection Maintained) Claim(s) 1, 2 and 4-20 are rejected under 35 U.S.C. 103 as being unpatentable over Dhakal et al. (Frontiers in Immunology, 2018, Vol. 9, Article 934) and Jiang et al. (Biomaterials, 2008, Vol. 29, pages 1931-1939).
The claimed invention is drawn to a nanoparticle comprising mannose conjugated
chitosan and an inactivated influenza A virus (IAV) antigen. The mannose chitosan encapsulates the inactivated IAV antigen. The nanoparticle further comprises a tripolyphosphate and the IAV antigen comprises inactivated swine IAV antigen or is from a H1N1, H1N2 or H3N2 virus. The composition comprising the nanoparticle is also part of a vaccine in a pharmaceutically acceptable carrier. The IAV is homologous, heterologous or heterosubtypic to an influenza A virus and it reduces transmission of the influenza A virus or reduces nasal shedding of the influenza A virus compared to a control within 4 days of exposure to the influenza A virus, or reduces the amount of influenza A in an upper respiratory tract of a subject by at least 1x10^1 TCID50/mL compared to a control.
The nanoparticle has a diameter of 500nm or less, or has an encapsulation efficiency of inactivated IAV antigen of at least 60%, or the nanoparticle elicits an increased amount of IgA antibody in a subject compared to a control.
Dhakal et al. teach the formulation of a mucoadhesive chitosan nanoparticles, which encapsulates inactivated (killed) antigens from a swine influenza virus. [see abstract and page 3] The swine influenza virus that provided the inactivated antigens is A/Swine/OH/FAH10-1/10 (H1N2) and Dhakal et al. refer to this nanoparticle composition as CNPs-KAg. [see first section of Materials and Methods] The nanoparticles encapsulated 67% of the influenza antigens and the formulation of these encapsulated antigens also included the addition of tripolyphosphate. [see left hand column of page 6 and left column of page 3] Following the formulation of the nanoparticle composition, Dhakal et al. teach the intranasal administration to piglets at a dosage of 10^7 TCID50 equivalent of inactivated antigen. [see Experimental Design section] The chitosan particles with killed influenza antigen containing nanoparticles are structurally the same as those of applicant’s invention and had a diameter of about 500 nm. [see right column of page 11] The encapsulation rate is higher than applicant’s minimum amount of at least 60% and since the antigen is from an H1N2 virus, it is heterologous to other influenza viruses, such as H3N2. Dhakal et al. report increased IgA levels in piglets following vaccination [see figures 3 and 5] reduced viral levels in the lungs of piglets [see Figure 8]. The administration of these nanoparticles to the piglets involved formulating the nanoparticles in a pharmaceutically acceptable carrier and therefore meets the requirements of a vaccine. The administration of these nanoparticles to piglets achieved reducing transmission of influenza A and eliciting an immune response since Dhakal et al. teach administering the same composition presently claimed to pigs intranasally and immune responses were observed.
However, Dhakal et al. do not teach the use of mannose conjugated to chitosan.
Jiang et al. teach chitosan nanoparticles with conjugated mannose to encapsulate killed antigens of bacteria. They also teach that mannose can facilitate macrophage uptake. [see page 1-introduction] Jiang et al. teach that incorporating mannose improves delivery of the antigen to mice intranasally. [see section 2.4.1] Mice receiving the mannose chitosan containing killed antigen exhibited a survival rate of 70%. [see section 3.3.3]
It would have been obvious to one of ordinary skill in the art to modify the compositions and methods taught by Dhakal et al. in order to employ mannose conjugated to the chitosan nanoparticles. One would have been motivated to do so, given the suggestion by Dhakal et al. chitosan nanoparticles can facilitate delivery of inactivated influenza antigens and achieve immune responses capable of reducing influenza infections. There would have been a reasonable expectation of success, given the knowledge that including mannose conjugated to chitosan particles with encapsulated killed bacterial antigens improved immune responses through macrophage targeted uptake, as taught by Jiang et al. Furthermore, the claim limitations of: reduces transmission of influenza A virus, reduces the nasal shedding of influenza A virus, reduces the amount of influenza A virus in the upper respiratory tract of a subject by at least 1x10^1TCID50/mL compared to a control, reduces the amount of the influenza virus within 4 days of exposure to the influenza A virus, and an increased amount of IgA antibody in respiratory tract of the subject compared to a control is also elicited, are obvious features of the nanoparticles one of ordinary skill in the art would arrive at based on the teachings of Dhakal et al. and Jiang et al.
Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Applicants argue that the particles of Dhakal would be larger than applicant’s claimed invention because the particles of Dhakal only comprise chitosan and tripolyphosphate and those particles are around 500nm in diameter, while the claimed invention is the same diameter or less and also comprises a mannose conjugated to the nanoparticle.
In response, claim 3 previously recited “wherein the nanoparticle has a diameter of 500nm or less”. This limitation is not the same as applicant’s amendment to claim 1 in the claims filed on 5/7/26. Claim 1 presently states “wherein the nanoparticle has an average diameter of 500nm or less”. The limitation of “has an average diameter” is interpreted to include diameters that may exceed 500 nm or be less than 500nm. Additionally, the instant claims do not indicate how much mannose is conjugated to chitosan. Depending on the amount of mannose conjugated, the size of the nanoparticle would vary. Therefore, the combined teachings of Dhakal et al. and Jiang et al. render prima facie obvious to one of ordinary skill in the art at the time the invention was made.
In addition, applicants argue that their mannose-chitosan nanoparticle encapsulating an inactivated influenza A virus antigen is able to induce a greater cross-reactive IgG antibody response (compared to chitosan nanoparticles lacking mannose) following intranasal vaccination in pigs. However, applicants claimed invention is not commensurate in scope with these unexpected results. The claimed invention of claim 1 at least does not specify what the influenza A antigen is while applicant’s working example (see page 34 of specification) involves inactivated influenza virus of a specific H1N2 serotype. A summary of the IgA and IgG responses to vaccines is provided in Figure 1, which shows similar cross-reactive IgA antibodies for H1N1-OH7 (panel B) and different cross-reactive IgA antibody titers relative to H3N2-OH4 (panel C). However, for cross-reactive IgG antibodies, whether mannose was included or not, the nanoparticle did not exhibit different antibody responses (see panels D-F). Therefore, applicants arguments related to unexpected results is not persuasive.
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Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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