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 .
Disposition of Claims
Claims 1-15 are pending and will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2024/0293528 A1, Published 05 September 2024. Applicant’s amended Specification as presented on 14 May 2024 is acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
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.
The information disclosure statements filed on 05 August 2024 and 01 December 2025 fail to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because they contain duplicate references. Specifically, Non-Patent Literature Document 1, Bhuyan et al., on the IDS filed on 05 August 2024 was already listed on the IDS filed on 14 May 2024 and a copy was provided at the time of that submission. As such, this duplicate reference has not been considered. This same reference was also listed on the IDS filed on 01 December 2025 and yet another copy was submitted then. Again, this duplicate reference has not been considered.
Also, Non-Patent Literature Document 14, Snoek et al., on the IDS filed on 01 December 2025 was already listed on the IDS filed on 05 August 2024 and a copy was provided at the time of that submission. As such, this duplicate reference has not been considered.
Additionally, the Talhouk et al. reference is listed twice on the IDS filed on 05 August 2024 and two copies were submitted. This reference has only been considered once.
These references have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
The information disclosure statements (IDSes) submitted on 18 April 2024, 14 May 2024, 06 June 2024, 05 August 2024, 18 October 2024, 14 March 2025, 08 October 2025, 01 December 2025, and 21 April 2026 have been considered by the examiner. Any individual references with strikethroughs, however, have not been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it contains language which can be implied in the form of the word “described”. It is suggested that “described” be replaced with “provided”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The use of the terms, CELLECTRA, cobas, Gardasil, Silgard, and Cervarix, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include the proper symbols indicating use in commerce such as ™, SM , or ® following the respective terms.
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.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1-2 objected to because of the following informalities: In Claim 1, it is suggested that it say “high-grade” instead of “high grade”. The hyphen is missing.
In Claim 2, it is suggested that it say “cervical HSIL” or “HSIL of the cervix” instead of “HSIL”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 1, and dependent claims 2-15 thereof, 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 1, it recites the limitation “A method of treating human papillomavirus (HPV) type 16- or HPV type 18-related high grade cervical intraepithelial lesion (HSIL), said method comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof.” Based on the title and various places throughout the instant Specification, “HSIL” appears to be an abbreviation for “high-grade squamous intraepithelial lesion” and the term appears to a general term for abnormal, precancerous cells on the surface of organs like the cervix, vagina, vulva, anus, and esophagus. The wording of the claim, however, appears to imply that “HSIL” instead stands for “high-grade cervical intraepithelial lesion” and that it is specific for the cervix. It is unclear if Applicant is attempting to define or redefine “HSIL” to be used only in the context of the cervix. This lack of clarity renders the claim indefinite. It is suggested that the phrase “high-grade cervical intraepithelial lesion (HSIL)” in Claim 1 be amended to instead recite “cervical high-grade squamous intraepithelial lesion (HSIL)” or “high-grade squamous intraepithelial lesion (HSIL) of the cervix”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 1 is rejected on the grounds of being indefinite. Claims 2-15 are also rejected since they depend upon Claim 1, but do not remedy the deficiencies of Claim 1.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Note: For the purpose of examining these claims on their merits, the limitations recited in dependent claims 7-14 are intended results and they have not been given patentable weight. If the prior art meets the limitations of instant Claim 1 or renders the limitations of instant Claim 1 obvious, then dependent Claims 7-14 simply reciting intended results and would be expected by the prior art. The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. > See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002)(finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). < In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id.
Claim Rejections - 35 USC § 112(a); First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the biological deposit enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
VGX-3100 is required to practice the claimed invention because VGX-3100 is a required element of the invention. As a required element it must be known and readily available to the public or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the enablement requirements of 35 U.S.C. § 112, first paragraph, may be satisfied by a deposit of VGX-3100. See 37 CFR 1.802. One cannot practice the claimed invention without VGX-3100. Therefore, access to VGX-3100 is required to practice the invention. The specification does not provide a repeatable method for readily identifying VGX-3100 without access to VGX-3100 and it does not appear to be readily available material.
Deposit of VGX-3100 in a recognized deposit facility would satisfy the enablement requirements of 35 U.S.C. 112, because the strains would be readily available to the public to practice the invention claimed, see 37 CFR 1.801- 37 CFR 1.809.
If a deposit is made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent, would satisfy the deposit requirements. See 37 CFR 1.808.
If a deposit is not made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made at an acceptable depository and that the following criteria have been met:
(a) during the pendency of this application, access to the invention will be afforded to one determined by the Commissioner to be entitled thereto;
(b) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years after the most recent request for the furnishing of a sample of the deposited material;
(d) a viability statement in accordance with the provisions of 37 CFR 1.807; and
(e) the deposit will be replaced should it become necessary due to inviability, contamination or loss of capability to function in the manner described in the specification.
In addition the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
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.
(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.
Claims 1, 3-5, and 7-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Trimble et al. (Trimble CL, Morrow MP, Kraynyak KA, Shen X, Dallas M, Yan J, Edwards L, Parker RL, Denny L, Giffear M, Brown AS, Marcozzi-Pierce K, Shah D, Slager AM, Sylvester AJ, Khan A, Broderick KE, Juba RJ, Herring TA, Boyer J, Lee J, Sardesai NY, Weiner DB, Bagarazzi ML. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015 Nov 21;386(10008):2078-2088.).
Trimble et al. teach a method of treating HPV-related HSIL comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof (see Page 2078, Methods and Findings Paragraphs).
Trimble et al. also teach a method wherein subjects were administered 6 mg of VGX-3100 intramuscularly followed by electroporation (see Page 2080, Left Column, Paragraph 3) three times in a twelve-week span (see Page 2080, Left Column, Paragraph 2).
Additionally, Trimble et al. teach a method wherein the result of VGX-3100 administration is evaluated at 36 weeks following administration of VGX-3100 (see Page 2078, Methods Paragraph; Page 2080, Right Column, Paragraphs 2-5; Page 2083, Left Column, Last Paragraph; Page 2084, Right Column, Paragraph 2; Page 2085, Left Column, First Paragraph).
Furthermore, Trimble et al. teach a method wherein the administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL, histopathologic regression of cervical HSIL, wherein administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18, complete histopathologic regression of cervical HSIL to normal, complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18, histopathologic non-progression, clearance of HPV-16 and/or HPV-18 infection from noncervical anatomic locations, and improved humoral and cellular immune response to VGX-3100 following a third administration of VGX-3100 and at 36 weeks following administration of VGX-3100 as assessed relative to baseline (see, at least, Page 2078, Methods and Findings Paragraphs; Page 2080, Right Column, Paragraphs 2-5; Page 2083, Left Column; Page 2084, Right Column, Paragraph 2; Page 2085, Left Column, Paragraphs 1-2; Figures 2-3). Trimble teaches that the treatment course results in positive outcomes ranging from histological non-progression to complete virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL and the results of the treatment include varying degrees of histological regression and virologic clearance of HPV-16 and/or HPV-18 as well as an improvement of humoral and cellular immune responses (see, at least, Page 2078, Methods and Findings Paragraphs; Page 2080, Right Column, Paragraphs 2-5; Page 2083, Left Column; Page 2084, Right Column, Paragraph 2; Page 2085, Left Column, Paragraphs 1-2; Figures 2-3). While the term “non-progression” is not specifically used in the prior art reference, the prior art would have the same result as it is the same method steps treating the same population with the same product. As noted above in the Claim Interpretation section, the limitations recited in these dependent claims (7-14) are intended results and they have not been given patentable weight. As the prior art meets the limitations of instant Claim 1, dependent Claims 7-14 are simply reciting intended results and would be expected by the prior art. The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. > See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002)(finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). < In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id.
For at least these reasons, Trimble et al. teach the limitations of instant Claims 1-5 and 7-15 and anticipate the invention encompassed by said claims.
Claims 1-15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Morrow et al. (US 2023/0338502, earliest Priority Date 21 April 2022, copending Application # 18/300,588) (cited by Applicant on IDS filed on 05 June 2024).
The applied reference has a common Assignee/Applicant and two Inventors in common with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Morrow et al. teach a method of treating human papillomavirus (HPV) type 16- or HPV type 18-related cervical high-grade intraepithelial lesion (HSIL), said method comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof wherein HSIL is determined by biopsy (see Claims 1 and 5). Morrow et al. also a method wherein VGX-3100 is administered to the subject by intramuscular injection followed by electroporation, wherein VGX-3100 is administered to the subject at a dose of 6 mg, wherein VGX-3100 is administered to the subject three times over the course of 12 weeks, and wherein VGX-3100 is formulated at a concentration of 6 mg/ml in 150 mM sodium chloride and 15 mM sodium citrate (see Claims 6-9). Additionally, Morrow et al. teach a method wherein the result of VGX-3100 administration is evaluated at 36 weeks following administration of VGX-3100, wherein said administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL, histopathologic regression of cervical HSIL, wherein administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18, complete histopathologic regression of cervical HSIL to normal, complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18, histopathologic non-progression, clearance of HPV-16 and/or HPV-18 infection from noncervical anatomic locations, and improved humoral and cellular immune response to VGX-3100 following a third administration of VGX-3100 and at 36 weeks following administration of VGX-3100 as assessed relative to baseline (see Claims 10-18).
For at least these reasons, Morrow et al. teach the limitations of instant Claims 1-15 and anticipate the invention encompassed by said claims.
Claims 1-15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Morrow et al. (US 2024/0229152 A9, earliest Priority Date 25 October 2022, copending Application # 18/493,936).
The applied reference has a common Assignee/Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Morrow et al. teach a method of treating human papillomavirus (HPV) type 16- or HPV type 18-related cervical high-grade intraepithelial lesion (HSIL), said method comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof wherein HSIL is determined by biopsy (see Claims 1 and 5). Morrow et al. also teach a method wherein VGX-3100 is administered to the subject by intramuscular injection followed by electroporation, wherein VGX-3100 is administered to the subject at a dose of 6 mg, wherein VGX-3100 is administered to the subject three times over the course of 12 weeks, and wherein VGX-3100 is formulated at a concentration of 6 mg/ml in 150 mM sodium chloride and 15 mM sodium citrate (see Claims 6-9). Additionally, Morrow et al. teach a method wherein the result of VGX-3100 administration is evaluated at 36 weeks following administration of VGX-3100, wherein said administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL, histopathologic regression of cervical HSIL, wherein administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18, complete histopathologic regression of cervical HSIL to normal, complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18, histopathologic non-progression, clearance of HPV-16 and/or HPV-18 infection from noncervical anatomic locations, and improved humoral and cellular immune response to VGX-3100 following a third administration of VGX-3100 and at 36 weeks following administration of VGX-3100 as assessed relative to baseline (see Claims 10-18).
For at least these reasons, Morrow et al. teach the limitations of instant Claims 1-15 and anticipate the invention encompassed by said claims.
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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Trimble et al. (Trimble CL, Morrow MP, Kraynyak KA, Shen X, Dallas M, Yan J, Edwards L, Parker RL, Denny L, Giffear M, Brown AS, Marcozzi-Pierce K, Shah D, Slager AM, Sylvester AJ, Khan A, Broderick KE, Juba RJ, Herring TA, Boyer J, Lee J, Sardesai NY, Weiner DB, Bagarazzi ML. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015 Nov 21;386(10008):2078-2088.), Ramos et al. (US 2021/0353736 A1, Published 18 November 2021), and Bhuyan et al. (Bhuyan PK, Dallas M, Kraynyak K, Herring T, Morrow M, Boyer J, Duff S, Kim J, Weiner DB. Durability of response to VGX-3100 treatment of HPV16/18 positive cervical HSIL. Hum Vaccin Immunother. 2021 May 4;17(5):1288-1293.).
Trimble et al. teach a method of treating HPV-related HSIL comprising administering a therapeutically effective amount of VGX-3100, which comprises two DNA plasmids, to a subject in need thereof (see Page 2078, Methods and Findings Paragraphs).
Trimble et al. also teach a method wherein subjects were administered 6 mg of VGX-3100 intramuscularly followed by electroporation (see Page 2080, Left Column, Paragraph 3) three times in a twelve-week span (see Page 2080, Left Column, Paragraph 2).
Additionally, Trimble et al. teach a method wherein the result of VGX-3100 administration is evaluated at 36 weeks following administration of VGX-3100 (see Page 2078, Methods Paragraph; Page 2080, Right Column, Paragraphs 2-5; Page 2083, Left Column, Last Paragraph; Page 2084, Right Column, Paragraph 2; Page 2085, Left Column, First Paragraph).
Furthermore, Trimble et al. teach a method wherein the administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL, histopathologic regression of cervical HSIL, wherein administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18, complete histopathologic regression of cervical HSIL to normal, complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18, histopathologic non-progression, clearance of HPV-16 and/or HPV-18 infection from noncervical anatomic locations, and improved humoral and cellular immune response to VGX-3100 following a third administration of VGX-3100 and at 36 weeks following administration of VGX-3100 as assessed relative to baseline. Trimble teaches that the treatment course results in positive outcomes ranging from histological non-progression to complete virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL and the results of the treatment include varying degrees of histological regression and virologic clearance of HPV-16 and/or HPV-18 as well as an improvement of humoral and cellular immune responses (see, at least, Page 2078, Methods and Findings Paragraphs; Page 2080, Right Column, Paragraphs 2-5; Page 2083, Left Column; Page 2084, Right Column, Paragraph 2; Page 2085, Left Column, Paragraphs 1-2; Figures 2-3).
Trimble et al. does not teach a method of treating HPV-related HSIL comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof wherein VGX-3100 is formulated at a concentration of 6 mg/mL in 150 mM sodium chloride and 15 mM sodium citrate or a method wherein the HPV-16 or HPV-18-related HSIL is determined by a biopsy.
Ramos et al. teach methods of inducing immune responses against HPV and treating infections caused by HPV comprising administering pharmaceutical or immunogenic compositions comprising recombinant DNA plasmids (see Abstract). Ramos et al. also teach wherein said compositions comprise two DNA plasmids encoding antigens from two different types of HPV formulated at a concentration of 6 mg/mL in 150 mM sodium chloride and 15 mM sodium citrate and are administered to subjects by intramuscular injection followed by electroporation (see Paragraph 0055, 0361-0362).
Bhuyan et al. teach long-term efficacy of VGX-3100 treatment of HPV-16 or HPV-18-related HSIL (see Abstract), wherein the HSIL is determined by a biopsy, specifically a Pap test (see Page 1290, Left Column, Last Paragraph and Right Column, First Paragraph).
A person having ordinary skill in the art would have been motivated to combine the teachings of Trimble et al. with those of Ramos et al. and Bhuyan et al. in order to develop a method of treating HPV-related HSIL comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof. A skilled artisan would have been motivated to modify the method of Trimble et al. by using the formulation buffer of Ramos et al. for the administration of VGX-3100 because the buffered solution would resist changes in pH, making the pharmaceutical composition comprising the VGX-3100 more stable and safer for administration. Additionally, there would have been an expectation of success as the buffer of Ramos et al. was successfully used in a similar method and with a similar product to the ones disclosed by Trimble et al. Using the method of Bhuyan et al. to identify HPV-16 or HPV-18-related HSIL would have been obvious to a skilled artisan because performing a Pap test is well-known in the art and a routine method in the context of HPV infections. While the term “non-progression” is not specifically used in the prior art reference, the prior art would have the same result as it is the same method steps treating the same population with the same product. As noted above in the Claim Interpretation section, the limitations recited in these dependent claims (7-14) are intended results and they have not been given patentable weight. As the prior art renders the limitations of instant Claim 1 obvious, dependent Claims 7-14 are simply reciting intended results and would be expected by the prior art. The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. > See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002)(finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). < In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. Therefore, the obvious method contains the same steps as the instant claims and so the intended results will necessarily occur, even if they were given patentable weight, which they have not.
Such modifications, combining the teachings of the prior art in order to yield a predictable result, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, instant Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
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.
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Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-18 of copending Application No. 18/300,588 (reference application) (cited by Applicant on IDS filed on 05 June 2024 as US 2023/0338502 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating human papillomavirus (HPV) type 16- or HPV type 18-related cervical high-grade intraepithelial lesion (HSIL), said method comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof wherein HSIL is determined by biopsy. Both claims are also drawn to a method wherein VGX-3100 is administered to the subject by intramuscular injection followed by electroporation, wherein VGX-3100 is administered to the subject at a dose of 6 mg, wherein VGX-3100 is administered to the subject three times over the course of 12 weeks, and wherein VGX-3100 is formulated at a concentration of 6 mg/ml in 150 mM sodium chloride and 15 mM sodium citrate. Both claim sets are also drawn to a method wherein the result of VGX-3100 administration is evaluated at 36 weeks following administration of VGX-3100, wherein said administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL, histopathologic regression of cervical HSIL. 9 The method of claim 1, wherein administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18, complete histopathologic regression of cervical HSIL to normal, complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18, histopathologic non-progression, clearance of HPV-16 and/or HPV-18 infection from noncervical anatomic locations, and improved humoral and cellular immune response to VGX-3100 following a third administration of VGX-3100 and at 36 weeks following administration of VGX-3100 as assessed relative to baseline.
The main difference between the instant claims and the reference claims is that the reference claims are also drawn to administration of VGX-3100 to a subject with cervical HSIL who is also categorized as biomarker positive for an miRNA signature based on normalized levels of various miRNAs, while the instant claims do not specify such a limitation. As such, the reference claims are a species of the genus recited by the instant claims and thus the reference claims anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-18 of copending Application No. 18/493,936 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating human papillomavirus (HPV) type 16- or HPV type 18-related cervical high-grade intraepithelial lesion (HSIL), said method comprising administering a therapeutically effective amount of VGX-3100 to a subject in need thereof wherein HSIL is determined by biopsy. Both claims are also drawn to a method wherein VGX-3100 is administered to the subject by intramuscular injection followed by electroporation, wherein VGX-3100 is administered to the subject at a dose of 6 mg, wherein VGX-3100 is administered to the subject three times over the course of 12 weeks, and wherein VGX-3100 is formulated at a concentration of 6 mg/ml in 150 mM sodium chloride and 15 mM sodium citrate. Both claim sets are also drawn to a method wherein the result of VGX-3100 administration is evaluated at 36 weeks following administration of VGX-3100, wherein said administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18 and histopathologic regression of cervical HSIL, histopathologic regression of cervical HSIL. 9 The method of claim 1, wherein administration of VGX-3100 results in virologic clearance of HPV-16 and/or HPV-18, complete histopathologic regression of cervical HSIL to normal, complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18, histopathologic non-progression, clearance of HPV-16 and/or HPV-18 infection from noncervical anatomic locations, and improved humoral and cellular immune response to VGX-3100 following a third administration of VGX-3100 and at 36 weeks following administration of VGX-3100 as assessed relative to baseline.
The main difference between the instant claims and the reference claims is that the reference claims are also drawn to evaluating one or more biological samples from a subject who has HPV type 16- or HPV type 18-related HSIL for the presence of a set of miRNAs and isomiRs thereof, calculating normalized levels for each of the miRNAs and isomiRs thereof in the set, determining an miRNA signature based on normalized levels of the miRNAs and isomiRs thereof in the set, categorizing the subject as biomarker positive or biomarker negative based on the miRNA signature and then administering a therapeutically effective amount of VGX-3100 to said subject if the subject is categorized as biomarker positive, while the instant claims do not specify such limitations regarding the miRNAs and isomiRs thereof or biomarkers. As such, the reference claims are a species of the genus recited by the instant claims and thus the reference claims anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Weiner and Yan (US 2010/0189730 A1, Published 29 July 2010)
Weiner and Yan teach pGX3002, which is one of the two plasmids comprised by VGX-3100. This reference has not been utilized as rejection would have been redundant to those set forth above.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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