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 1-18 and 21-22 are pending in the application.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 10/15/2025 is acknowledged. The traversal is on the ground(s) that should the composition claims be found allowable, the dependent method should also be found allowable.
This is not found persuasive because the elected composition claims are not allowable at present. The issue of rejoinder will be revisited once the composition claims are allowable.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 21 and 22 are withdrawn from consideration for being directed to non-elected subject matter. Claims 1-18 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/5/2023 and 12/11/2024 have been considered by the examiner.
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.
Claims 2-5, 10, 12-18 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.
Regarding claim 2, the recitation of “wherein the one or more DNA molecules comprise (1) a nucleotide sequence encoding a triclosan selection sequence and (2) one or more nucleotide sequences encoding a fusion protein comprising at least one of the one or more antigens and one or more polyubiquitin sequences” renders the claim indefinite because it is unclear whether claim 2 is limited to the above two recited elements, or encompasses additional element(s) as recited in parent claim 1. It is unclear what is being claimed in the context of claim 1, wherein it recites different elements in (1) and (2).
Regarding claim 3, the recitation of “wherein the one or more DNA molecule comprise (1) a nucleotide sequence encoding a triclosan selection sequence and (2) one or more expression-enhancing intron sequences” renders the claim indefinite because it is unclear whether claim 3 is limited to the above two recited elements, or encompasses additional element(s) as recited in parent claim 1. It is unclear what is being claimed in the context of claim 1, wherein it recites different elements in (1) and (2).
Regarding claim 4, the recitation of “wherein at least one of the more or more DNA molecules comprises (1) one or more nucleotide sequences encoding a fusion protein comprising at least one of the one or more antigens and one or more polyubiquitin sequences and (2) one or more expression-enhancing intron sequences” renders the claim because it is unclear whether claim 4 is limited to the above two recited elements, or encompasses additional element(s) as recited in parent claim 1. It is unclear what is being claimed in the context of claim 1, wherein it recites different elements in (1) and (2).
Regarding claim 5, the recitation of “wherein at least one of the one or more DNA molecules comprise (1) one or more nucleotide sequences encoding a fusion protein comprising at least one of the one or more antigens and one or more polyubiquitin sequences and (2) one or more expression-enhancing intron sequences and (3) at least one of the one or more DNA molecules comprises a nucleotide sequence encoding a triclosan selection sequence” renders the claim because it is unclear whether claim 5 is limited to the above three recited elements, or encompasses additional element(s) as recited in parent claim 1. It is unclear what is being claimed in the context of claim 1, wherein it recites different elements in (1)-(3).
Regarding claims 12 and 18, the recitation of “wherein…(1)…(4)” renders the claim indefinite because the limitation in (1)-(4) are completely different from (1)-(4) are recited in parent claim 1, and it is unclear whether claim 12 is limited to the above three recited elements, or encompasses additional element(s) as recited in parent claim 1 and claim 5. It is unclear what is being claimed in the context of claim 1, wherein it recites different elements in (1)-(4).
Regarding claims 10 and 17, the term “significant proportion of a population of a species of animals” renders the claim indefinite because it is unclear what “proportion” would be considered “significant” to induce immune response of said animal species. As such, the metes and bounds of the claim cannot be established.
Dependent claims 13-18 are rejected for same reason because they depend on claim 5 but does not remedy the indefiniteness of claim 5.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 6, 7, 9-12 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Alcolea (WO2016188973).
Claim 1 is drawn to a composition comprising: (1) an effective amount of one or more DNA molecules comprising: (a) one or more nucleotide sequences that encode one or more antigens and (b) a nucleotide sequence comprising a sequence encoding a triclosan selection sequence; (2) one or more types of functionalized calcium phosphate nanoparticles that are associated with at least some of the one or more DNA molecules; (3) a carrier for mucosal administration and (4) one or more adjuvant.
Alcolea teaches FabI gene boosts immunogenicity of DNA vaccines when co-administered as a molecular adjuvant with an antigen of interest (page 4, lines 15-18). Alcolea teaches FabI gene encodes an enoyl-acyl carrier protein (ACP) reductase which is an essential enzyme for bacterial fatty acid synthesis and sensitive to triclosan, a molecular selection marker for molecular cloning. Alcolea teaches the selection mechanism is not based on the existence of a gene for resistance to the selection agent, but on increasing the concentration of the enoyl-ACP reductase protein in the cytoplasm in those clones which acquire the foreign DNA (page 18-19, bridging paragraph). Alcolea teaches the polynucleotide encoding the FabI is preferably co-administered with a nucleic acid sequence encoding one or more antigens, which may be in the same polynucleotide sequence or in a different polynucleotide sequence (page 21, lines 16-21). Alcolea teaches the composition further comprising a pharmaceutical acceptable carrier, additive or excipient (page 34, lines 1-5). Alcolea teaches the suitable carrier include calcium phosphates (page 34, line 18). Alcolea teaches the pharmaceutical composition may further comprise adjuvants (page 35, lines 15-18). Alcolea teaches suitable carrier for the vaccine composition includes microparticles such as PLG, and liposomes (page 35, lines 5-8, page 34, lines 25-29), which meets the limitation of carrier that are suitable for mucosal administration. Therefore, the teaching from Alcolea anticipates the composition of claim 1.
Regarding claim 6, Alcolea teaches adjuvant of the vaccine include killed bacterial and bacterial components (page 35, lines 23-24).
Regarding claim 7, Alcolea teaches adjuvant of the vaccine include polysaccharide particles (page 35, line 24).
Regarding claims 9 and 11, Alcolea teaches the antigen in pPAL-LACK vector is obtained from pCI-neo-LACK (page 50, section 1.2), which is a naturally occurring antigenic sequence from Leishmania infantum that causes visceral leishmaniasis in dogs (page 2, lines 26-27).
Regarding claim 10, Alcolea teaches administration LACK DNA promote protective immunity in mice (page 2, lines 27-30). Since the claim does not clearly define “significant proportion,” the teaching from Alcolea meets the claim limitation.
Regarding claim 12, Alcolea teaches the polynucleotide sequence encoding triclosan selection sequence FabI is preferably co-administered with a nucleic acid sequence encoding one or more antigens, wherein the antigen coding sequence could be found either in the same polynucleotide sequence or in a different polynucleotide sequence, being in the same composition or different composition (page 21, lines 17-24). In the case of the polynucleotide encoding FabI and the antigen encoding polynucleotide are in two different polynucleotide, it meets the limitation that at least one of the DNA molecule of the two DNA molecules comprise at least one nucleotide sequence that is not contained in at least one other DNA molecule of the at least two DNA molecules; (2) encodes at least one expression product that is different from the expression product from other DNA molecule; (3) at least one of the at least two DNA molecule encodes antigen that induce an immune response against a disease-causing agent; and (4) at least one of the at least two DNA molecule does not encode any antigens that induce immune response against the disease causing agent (the triclosan sequence FabI does not cause immune response by itself).
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.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alcolea, in view of Jin et al (Vaccine, 2018, Vol.36, pages 5235-5244).
The teaching from Alcolea has been discussed above.
However, Alcolea does not specifically teach βglucan as adjuvant.
Jin teaches βglucan is a group of polysaccharides exits in many organism species including mushroom, yeast, oats, barley, seaweed and have a variety of biological activities (abstract). Jin teaches βglucan can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines (Table 2, page 5238, 1st col., 2nd paragraph, 2nd col., 2nd paragraph, and Table 3).
It would have been obvious to an ordinary skilled in the art that βglucan may be used as an adjuvant to the vaccine composition taught by Alcolea. The ordinary skilled in the art would be motivated to use βglucan adjuvant because of its known immuno-potentiating effect taught by Jin, and would have reasonable expectation of success following combined teaching from Alcolea and Jin. Therefore, the claimed invention would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 2-5, 13, 14, 16 , 17 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alcolea, in view of Wang et al (DNA and Cell Biology, 2012, Vol. 31, No.4, pages 489-495) and Xu et al (Gene, 2001, Vol.272, pages 149-156).
The teaching from Alcolea has been discussed above. Alcolea also teaches the promoter that directs nucleic acid expression is CMV enhancer/promoter (page 30, line 10, and Figure 2).
However, Alcolea does not teach inclusion of polyubiquitin sequences fusion of the antigen (claim 2), and/or one or more expression enhancing intron sequence(s) with triclosan selection sequence (claim 3-5).
Wang teaches cellular immune response is improved by a ubiquitin-fused DNA vaccine against Mycobacterium tuberculosis (abstract). Wang teaches the production of Th1 cytokine and proliferative T cell responses were enhanced significantly in mice immunized with Ub-fused MPT64 DNA vaccine (page 494, 1st col., 2nd paragraph, lines 8-12).
Xu et al. teaches a method of optimization of transcriptional regulatory elements for constructing vectors that promote efficient gene expression (abstract). Xu et al. teaches inclusion of CMV intron sequence to a plasmid that comprises CMV promoter/enhancer generates 2-6 fold in vitro and 1.5-3 fold in vivo higher levels of reporter expression (page 152, 1st col., 16-20).
It would have been obvious to an ordinary skilled in the art to modify the polynucleotide molecule taught by Alcolea with addition of intron A from CMV (taught by Xu) and ubiquitin sequence (taught by Wang) to improve the effect of the vaccine. The ordinary skilled in the art would have been motivated adding intron A from CMV, which has demonstrated higher transgene expression by Xu, and making an ubiquitin fusion to improve immune response as demonstrated by Wang. The ordinary skilled in the art would have reasonable expectation of success to add intron A and ubiquitin sequence to the polynucleotide construct taught by Alcolea following combined teaching of Alcolea, Wang and Xu. Therefore, the claimed invention of claims 2-5 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 13, Alcolea teaches adjuvant of the vaccine include killed bacterial and bacterial components (page 35, lines 23-24).
Regarding claim 14, Alcolea teaches adjuvant of the vaccine include polysaccharide particles (page 35, line 24).
Regarding claims 16, Alcolea teaches the antigen in pPAL-LACK vector is obtained from pCI-neo-LACK (page 50, section 1.2), which is a naturally occurring antigenic sequence from Leishmania infantum that causes visceral leishmaniasis in dogs (page 2, lines 26-27).
Regarding claim 17, Alcolea teaches administration LACK DNA promote protective immunity in mice (page 2, lines 27-30). Since the claim does not clearly define “significant proportion,” the teaching from Alcolea meets the claim limitation.
Regarding claim 18, Alcolea teaches the polynucleotide sequence encoding triclosan selection sequence FabI is preferably co-administered with a nucleic acid sequence encoding one or more antigens, wherein the antigen coding sequence could be found either in the same polynucleotide sequence or in a different polynucleotide sequence, being in the same composition or different composition (page 21, lines 17-24). In the case of the polynucleotide encoding FabI and the antigen encoding polynucleotide are in two different polynucleotide, it meets the limitation that at least one of the DNA molecule of the two DNA molecules comprise at least one nucleotide sequence that is not contained in at least one other DNA molecule of the at least two DNA molecules; (2) encodes at least one expression product that is different from the expression product from other DNA molecule; (3) at least one of the at least two DNA molecule encodes antigen that induce an immune response against a disease-causing agent; and (4) at least one of the at least two DNA molecule does not encode any antigens that induce immune response against the disease causing agent (the triclosan sequence FabI does not cause immune response by itself).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alcolea, Wang and Xu, as applied to claims 5 and 13 and 14 above, and further in view of Jin.
The teaching from Alcolea, Wang and Xu has been discussed above.
However, none of the reference specifically teach βglucan as adjuvant.
Jin teaches βglucan is a group of polysaccharides exits in many organism species including mushroom, yeast, oats, barley, seaweed and have a variety of biological activities (abstract). Jin teaches βglucan can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines (Table 2, page 5238, 1st col., 2nd paragraph, 2nd col., 2nd paragraph, and Table 3).
It would have been obvious to an ordinary skilled in the art that βglucan may be used as an adjuvant to the vaccine composition taught by rendered obvious by combined teaching from Alcolea, Wang and Xu. The ordinary skilled in the art would be motivated to use βglucan adjuvant because of its known immuno-potentiating effect taught by Jin, and would have reasonable expectation of success following combined teaching from Alcolea and Jin. Therefore, the claimed invention of claim 15 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637