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 .
Election/Restrictions
Applicant’s election without traverse of the following species: i) intramuscular injection, ii) wherein the method provides an improvement in RRP staging (claim 16), and iii) wherein the HPV6 antigenic domain and the HPV 11 antigenic domain are separated by one or more post-translational cleavage sites, one or more translational skipping sites, or both (claim 21) in the reply filed on 7/13/2026 is acknowledged.
Status of the Claims
Claims 7-12, 22 and 23 have been withdrawn as being directed to a non-elected species. Claims 1, 3, 16-21, 24-28, and 30-36 are under examination at this time.
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.
Claim 24 is 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 24, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h).
The term optionally means “not required or mandatory”. For example, a composition comprising A, B, C, and optionally D means that component D can or cannot be present (D is not required to be present). In claim 24, it appears the use of “optionally” is an attempt to define “preferred” embodiments or limitations. For example, claim 24 states that the nucleic acid is “an expression vector, optionally a plasmid”. In this instance, the term optionally does not make sense given the definition of optionally (not required or mandatory).
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.
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.
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) 1, 3, 16-17, 24, 26, 33, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al. (Human Vaccines & Immunotherapeutics, 2012, 8(4):470-478).
The instant claims are directed to a method of treating or preventing recurrent respiratory papillomatosis (RRP) in a subject in need thereof, said method comprising intramuscularly administering to the subject an effective amount of a pharmaceutical composition comprising a nucleic acid molecule encoding a human papillomavirus (HPV) antigen comprising a HPV6 antigenic domain and a HPV 11 antigenic domain, wherein the HPV6 antigenic domain is an HPV6 E6-E7 fusion antigen and wherein the HPV 11 antigenic domain is an HPV 11 E6-E7 fusion antigen, to thereby treat or prevent RRP.
Shin et al. teaches that “low-risk” subtypes of HPV, HPV6 and HPV11, are the major cause of recurrent respiratory papillomatosis and genital warts (see the abstract). Shin et al. discloses two engineered DNA vaccines that encode HPV 6 and 11 consensus E6/E7 fusion proteins (p6E6E7 and p11E6E7, respectively) by utilizing a multi-phase strategy. Vaccination was performed as follows: Each mouse received three doses of 20 μg of each DNA plasmid at 14-day intervals. Mice in the group receiving both p6E6E7 and p11E6E7 together received 20 μg of each plasmid for a total of 40 μg of DNA per vaccination. The DNA constructs were administered via intramuscular injection of the right quadriceps muscle, followed by square-wave pulses generated by the CELLECTRA® constant current electroporation device (see page 476, right column) [claims 1 and 3].
Shin et al. does not teach a single nucleic acid molecule, as claimed, encoding a HPV6 antigenic domain and a HPV11 antigenic domain.
Shin et al. teaches that the HPV6 and HPV11 antigenic domains are encoded by separate nucleic acids. The expression of both constructs was confirmed by western blot analysis and immunofluorescence assay, and Shin et al. administered both nucleic acids at the same time. Therefore, it is obvious and well within the purview of one of ordinary skill in the art to use two nucleic acids or one nucleic acid encoding the HPV6 and HPV11 antigenic E6/E7 domains and the result would be predictable [expression of HPV6 E6/E7 and expression of HPV11 E6/E7].
Regarding claims 16 and 36, because the method of Shin et al. is the same as the claimed method, the method of Shin et al. will also provide improvement in RRP staging assessment scores relative to baseline, where the improvement comprises a decrease in total site score, a decrease in total clinical score, or both.
Regarding claim 17, Shin et al. teaches that HPV6 and HPV11 are the major cause of recurrent respiratory papillomatosis and Shin et al. teaches the same method as claimed. Accordingly, the method of Shin et al. will treat or prevent RRP in general, which would naturally include juvenile-onset and adult-onset RRP.
Regarding claim 24, Shin et al. teaches that the fusion genes encoding either HPV subtype 6 or 11 consensus E6/E7 fusion protein (6E6E7 or 11E6E7) were synthesized and sequence verified. The synthesized 6E6E7 or 11E6E7 was digested with BamHI and XhoI, cloned into the expression vector pVAX1 (Invitrogen, V26-20) under the control of the cytomegalovirus immediate-early promoter and these constructs were named as p6E6E7 or p11E6E7 (see page 475, right column).
Regarding claim 26, Shin et al. teaches that genetic adjuvants may be used to further boost the immune response of p6E6E7 and p11E6E7 post-vaccination (see page 474, right column).
Regarding claim 33, Shin et al. teaches the administration of both p6E6E7 and p11E6E7 together (20 μg of each plasmid for a total of 40 μg of DNA per vaccination). Shin et al. does not indicate the amount of DNA per milliliter of buffer.
Determining other effective dosages of HPV DNA is routine experimentation. Shin et al. teaches the use of 40 μg of DNA for p6E6E7 and p11E6E7 together. It is obvious and routine to determine the necessary amount of an agent that needs to be administered to achieve a desired effect. Further, applicant has not demonstrated unexpected results for the claimed amounts of HPV antigen per milliliter of buffer.
Furthermore, according to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”)
Thus, the invention, as a whole, was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim(s) 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al. (Human Vaccines & Immunotherapeutics, 2012, 8(4):470-478) as applied to claims 1, 3, 16-17, 24, 26, 33 and 36 above, and further in view of Wang et al. (Synthetic and Systems Biotechnology, 2021, 6:254–261).
The instant claims are directed to the method of claim 1 wherein the nucleic acid sequence encoding the HPV 11 antigenic domain is located 5' to the nucleic acid sequence encoding the HPV6 antigenic domain (claim 20) or wherein the HPV6 antigenic domain and the HPV 11 antigenic domain are separated by one or more post-translational cleavage sites, one or more translational skipping sites, or both (claim 21).
The teachings of Shin et al. are outlined above and incorporated herein. Shin et al. does not teach the limitations of claims 20 and 21. However, Wang et al. teaches the use of post-translational cleavage sites (e.g., 2A) and translational skipping sites to separate genes within the same construct. Wang et al. states that for the co-expression in polycistronic vectors, 2A sequences, mostly derived from viral polyproteins, mediate a ribosome-skipping event such that several, different, separate proteins can be generated from a single open reading frame (see, for example, the abstract and Figure 2).
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods taught by Shin et al. and use the 2 A cleavage site between the HPV6 antigenic domain and the HPV11 antigenic domain when including both domains in a single nucleic acid construct. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Wang et al. [2 A sequences mediate a ribosome-skipping event such that several, different, separate proteins can be generated from a single open reading frame]. Give the teachings of Wang et al. outlined above, it would also be obvious for one of ordinary skill in the art to place the antigenic domains in any order (HPV6 followed by HPV11 or HPV11 followed by HPV6) and the result would be predictable (the separate expression of the two antigenic domains).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim(s) 27-28 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al. (Human Vaccines & Immunotherapeutics, 2012, 8(4):470-478) as applied to claims 1, 3, 16-17, 24, 26, 33 and 36 above, and further in view of Yan et al. (Molecular Therapy, May 2015, 23(Supplement 1): S85).
The instant claims are directed to the method of claim 1 where the composition further comprises an adjuvant such as IL-12.
The teachings of Shin et al. are outlined above and incorporated herein. Shin et al. does not teach the use of IL-12 as an adjuvant or that the nucleic acid encoding the IL-12 is an expression vector.
Yan et al. teaches that antitumor immunity was enhanced by combining HPV16 and 18 E6/E7 DNA vaccine with IL-12 as an immuno-adjuvant. In a non-human primate model, a rhesus macaque IL-12 plasmid increased the magnitude of vaccine-induced cellular immune responses about two-fold post third immunization.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods taught by Shin et al. and include a plasmid encoding IL-12 to the vaccine composition. One would have been motivated to do so and there would have been a reasonable expectation of success given the findings of Yan et al. [IL-12 enhanced antitumor immunity of the HPV16 and 18 E6/E7 DNA vaccine].
Regarding claim 34, Yan et al. teaches the use of “an amount” of IL-12 plasmid to enhance the HPV16 and 18 E6/E7 DNA vaccine immune response. Yan et al. does not indicate the amount of IL-12 DNA per milliliter of buffer.
Determining the effective dosages of IL-12 DNA is routine experimentation. Yan et al. used an amount of IL-12 DNA that was effective for enhancing the immune response of the HPV16 and 18 E6/E7 DNA vaccine. Thus, it is obvious and routine to determine the necessary amount of an agent that needs to be administered to achieve a desired effect. Further, applicant has not demonstrated unexpected results for the claimed amounts of IL-12 DNA per milliliter of buffer.
Furthermore, according to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”)
Thus, the invention, as a whole, was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim(s) 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al. (Human Vaccines & Immunotherapeutics, 2012, 8(4):470-478) as applied to claims 1, 3, 16-17, 24, 26, 33 and 36 above, and further in view of Hollenberg et al. (Human Vaccines & Immunotherapeutics, 2020, 16(6):1404–1412).
The instant claims are directed to the method of claim 1 where the composition further comprises an excipient, such as a saline-sodium citrate buffer.
The teachings of Shin et al. are outlined above and incorporated herein. While Shin et al. teaches that the constructs p6E6E7 and p11E6E7 were administered via intramuscular injection, which would obviously include some sort of excipient or diluent. Shin et al. does not teach that the excipient or diluent was a saline-sodium citrate buffer. However, Hollenberg et al. teaches the intramuscular administration (with electroporation) of 6mg of VGX-3100 DNA plasmids in a saline sodium citrate (SSC) buffer. VGX-3100 is an immunotherapy that uses electroporation to introduce DNA encoding for modified HPV-16 and HPV-18, E6-and E7 proteins into myocytes.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods taught by Shin et al. and perform the IM administration with electroporation using known buffers, such as the saline sodium citrate (SSC) buffer taught by Hollenberg et al. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Hollenberg et al. outlined above.
Thus, the invention, as a whole, was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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, 17-19, 24-28 and 30-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 9-12, 17, 22-25, 28, 34 and 35 of U.S. Patent No. 11744885.
The instant claims are directed to a method of treating or preventing recurrent respiratory papillomatosis (RRP) in a subject in need thereof, said method comprising intramuscularly administering to the subject an effective amount of a pharmaceutical composition comprising a nucleic acid molecule encoding a human papillomavirus (HPV) antigen comprising a HPV6 antigenic domain and a HPV 11 antigenic domain, wherein the HPV6 antigenic domain is an HPV6 E6-E7 fusion antigen and wherein the HPV 11 antigenic domain is an HPV 11 E6-E7 fusion antigen, to thereby treat or prevent RRP.
The patented claims are directed to a method for treating or preventing recurrent respiratory papillomatosis (RRP) in a subject comprising administering to the subject an effective amount of a pharmaceutical composition to thereby treat or prevent RRP. The composition can comprise a nucleic acid molecule encoding a human papillomavirus (HPV) antigen comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 11; or an amino acid sequence that is at least 95% homologous to SEQ ID NO: 1 or SEQ ID NO: 11 and comprise a nucleotide sequence at least 95% homologous to SEQ ID NO: 2 or SEQ ID NO: 12 or the nucleotide sequence of SEQ ID NO: 2 or the nucleotide sequence of SEQ ID NO 12. The composition can further comprise an adjuvant which can be a nucleic acid encoding IL12, the p35 subunit of IL-12, the p40 subunit of IL-12, or both.
Patented claims 1, 2, 28 and 34 teach instant claims 1, 18 and 19.
Patented claim 35 teaches instant claim 3.
Patented claim 29 teaches instant claim 17.
Patented claims 3-4 teach instant claim 24.
Patented claim 5 teaches instant claim 25.
Patented claims 9-12, 17 and 22 teach instant claims 26-28.
Patented claims 23-25 teaches instant claims 30-34.
Patented claims 5, 20, 24 and 25 teach instant claim 35.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 3, 17, 21, 24, 26-28 and 30-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 10-12, 16, 18-19, and 23-26 of U.S. Patent No. 12478667.
The instant claims are directed to a method of treating or preventing recurrent respiratory papillomatosis (RRP) in a subject in need thereof, said method comprising intramuscularly administering to the subject an effective amount of a pharmaceutical composition comprising a nucleic acid molecule encoding a human papillomavirus (HPV) antigen comprising a HPV6 antigenic domain and a HPV 11 antigenic domain, wherein the HPV6 antigenic domain is an HPV6 E6-E7 fusion antigen and wherein the HPV 11 antigenic domain is an HPV 11 E6-E7 fusion antigen, to thereby treat or prevent RRP.
The patented claims are directed to a method for treating or preventing recurrent respiratory papillomatosis (RRP) in a subject comprising administering to the subject an effective amount of a pharmaceutical composition to thereby treat or prevent RRP. The composition can comprise a nucleic acid sequence encoding a human papillomavirus 11 (HPV11) E6 antigen, a nucleic acid sequence encoding a HPV11 E7 antigen, a nucleic acid sequence encoding a human papillomavirus 6 (HPV6) E6 antigen, and a nucleic acid sequence encoding a HPV6 E7 antigen. The composition can further comprise an excipient and adjuvant which can be a nucleic acid encoding IL12, the p35 subunit of IL-12, the p40 subunit of IL-12, or both.
Patented claims 23, 25, 10, and 1 teach instant claim 1.
The patent specification defines an antigen as proteins having an HPV6 E6 domain, HPV6 E7 domain, HPV11 E6 domain, HPV11 E7 domain, or any combination thereof, and preferably a fusion protein of an HPV6 E6 domain, HPV6 E7 domain, HPV11 E6 domain, and HPV11 E7 domain with an endoproteolytic cleavage site between each domain (see col. 7, line 65 to col. 8, line 16 and see col. 33, lines 25-34). Thus, the antigens in patented claim 1 can be fusion proteins.
Patented claim 26 teaches instant claim 3.
Patented claim 24 teaches instant claim 17.
Patented claim 4 teaches instant claim 21.
Patented claim 7 teaches instant claim 24.
Patented claims 11-12 teach instant claims 26-27, respectively.
Patented claim 16 teaches instant claim 28.
Patented claim 10 teaches instant claim 30.
Patented claims 18-19 teach instant claims 31-32, respectively.
Patented claim 20 teaches instant claims 33-34.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Allowable Subject Matter
SEQ ID NOs: 1, 2, 3, 11 and 12 are free of the prior art. Additionally, sequences that are 95% homologous to instant SEQ ID NOs: 1, 2, 11 and 12 are free of the prior art.
Conclusion
No claim is allo\w
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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