DETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant's election with traverse of Group I claims 1-11 and 23-25 in the reply filed on 03/13/2026 is acknowledged. The traversal is on the ground(s) that the Groups I and II are related as a process of use of a product (Group I) and the product (Group II).
This is not found persuasive because the special technical feature of the claimed product (composition) and methods of treatment is rendered obvious by the applied prior art and therefore Group I and II lack unity of invention.
Species election: In response to the species election, Applicant elects:
(i) Live or live-attenuated commensal human papilloma viruses. Claims 1-3, 8-11, and
23-25, and claims 12, 21, and 22 read on this election (Group II).
(ii) p-HPV. Claims 1-3, 8-11, and 23-25, and claims 12, 21, and 22 read on this election (Group II).
(iii) Poly-ICLC (carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L- lysine double-stranded RNA). Claims 1-8, 10, 11, and 23-25, and claims 12, and 21 read on
this election (Group II).
(iv) Topical imiquimod. Claims 1-11 and 23-25 read on this election.
The Group II claims and the reading of species on non-elected claims 12, 21, and 22 will not be examined.
Requirement for election of species from (i) antigenic peptide or (ii) live or live-attenuated commensal human papilloma viruses is withdrawn.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
3. Claims 1-12, and 21-25 as per filing of 03/13/2026 are pending.
4. Claims 12, 21-22 are withdrawn from consideration due to election/restriction.
5. Claims 1-11 and 23-25 are under examination.
Priority
6. This application is the U.S. National Phase Application under 35 U.S.C. 371 of
International Patent Application No. PCT/US2022/013228, filed on January 21, 2022, which
claims the benefit of U.S. Provisional Patent Application Serial No. 63/140,159, filed on January 21, 2021.
Information Disclosure Statement
7. The information disclosure statements (IDSs) submitted on 09/27/2023, 10/03/2023, 11/22/2023, 04/15/2024, 05/24/2024, 08/09/2024, 11/12/2024, 11/26/2024, 03/13/2026 was in time. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objection to Specification
8. 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.
Instant specification page 17-18 listed 7 references.
Claim Objections
9. Claim 3 is objected to because of the following informalities:
The instant claim 3 recited Table A as a limitation in the claim that requires refereeing to the specification. For clarity and completeness, the limitations from Table A are required to be recited in the claim 3. See MPEP 2173.05 (S ). Appropriate correction is required.
Claim Rejections - 35 USC § 112
10. 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 1-12 and 21-25 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.
MPEP 2173.05 (s) states: [Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim. See MPEP § 608.01(m) for information pertaining to the treatment of reference characters in a claim.] Presently, the claimed information of Table A does not meet the requirements of an “exceptional circumstances where there is no practical way to define the invention in words.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
To overcome the rejection applicant should consider placing the limitations from specification Table A to the instant claim 3.
Claim Rejections - 35 USC § 112 (Written Description)
11. 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 1-11 and 23-25 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The Instant claims 1-12 and 21-25 are broad because the independent claim 1 is very broad (See, claim 1 interpretation below).
The Instant claims 1-12 and 21-25 are based on specification of the instant application published US20240100141A1.
The broadest reasonable interpretation is that the claimed (i) antigenic peptides or (ii) live or live attenuated commensal HPVs of any or all serotypes/subtypes are administered in an effective amount to a subject to treat or reduce the risk of developing an HPV etiology mucosal cancer and as well as non-HPV etiology mucosal cancer. The mucosal cancer is interpreted to cancer of all mucosal surface of body (e.g. respiratory system, genital and urinal mucosa, skin, eye mucosal surface). The treatment is interpreted that the subject is already have a mucosal cancer. Reducing the risk is interpreted as reduction in possibility to develop a cancer but not prevention of a mucosal cancer.
The claim specification does not provide written description subject matter support for treatment of mucosal cancer of non-HPV etiology.
The claim 1 recites two methods embodiments:
(a) antigenic peptides (see, instant specification para [0006] – [0010], [0046] – [0047]).
(b) live HPVs or live-attenuated commensal HPVs (see, instant specification para [0005], [0019], [0033]).
The specification does not provide support for full scope of the claims 1-12 and 21-25 because applicant has claimed a genus of mucosal cancer and there is no written description of the claimed subject matter to support treatment of non-HPV etiology mucosal cancers.
Applicant has claimed a genus of attenuated Human Papilloma Virus (HPV). Attenuation is a functional limitation that requires a balance of reduced pathogenicity, immunogenicity and yet reasonably efficient replication to induce durable immune response and protection.
Thus, applicant has claimed two genera (i) mucosal cancer, (ii) attenuated Human Papilloma Virus (HPV).
When a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed. However, the presence of multiple species within a claimed genus does not necessarily demonstrate possession of the genus. See, In re Smyth, 178 U.S.P.Q. 279 at 284-85 (CCPA 1973) (stating “where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus or combination claimed at a later date in the prosecution of a patent application.”); and University of California v. Eli Lilly and Co., 43 USPQ2d 1398, at 1405 (Fed Cir 1997)(citing Smyth for support).
The applicable standard for the written description requirement can be found in MPEP§ 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. In the instant case, there are no structural features recited or provided in the specification except that “attenuated Human Papilloma Virus (HPV)”. There is no disclosure of structure, sequence (nucleotide and or amino acid), or physical properties of the starting material (parent virus sequence) or the finished material the attenuated HPV. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. The instant claims encompass an infinite genus of attenuated Human Papilloma Virus (HPV) that could be identical to any unidentified HPV viruses parental sequence starting material and sequence variants.
Amgen Inc. vs Sanofi (2017-1480, Fed Cir, 2017) states that "an adequate written description must contain enough information about the actual makeup of the claim products - a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material," which may be present in "function "terminology "when the art has established a correlation between structure and function" (page 17,1st paragraph).
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description” Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Fri. January 5, 2001, see especially page 1106 column 3). In the instant case, the specification does not provide adequate written description of an attenuated Human Papilloma Virus (HPV). The legal standard for sufficiency of a patent's (or a specification’s) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the claimed subject matter", Vas-Cath, Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention. The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
The instant specification lack 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.
Claim Rejections - 35 USC § 112 (Enablement)
12. Claims 1-12 and 21-25 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 enablement requirement. The claims contains subject matter of genus (i) mucosal cancer (that include non-HPV etiology mucosal cancer), and genus (ii) live HPVs or live-attenuated commensal HPVs 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 make and/or use the invention.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including the nature of the invention, the state of the prior art, the breadth of the claims, the amount of guidance in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, and the quantity of experimentation necessary. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention: Claims 1-12 and 21-25 are directed to a method of treating, or reducing the risk of developing, mucosal cancer in a subject, the method comprising administering to the subject an effective amount of a composition comprising: a plurality of (i) antigenic peptides, each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses, or (ii) live or live-attenuated commensal human papilloma viruses; and a T cell adjuvant that increases T cell response to the antigenic peptides. The mucosal cancer is interpreted to be claimed as both HPV etiological mucosal cancer as well as non-HPV etiological mucosal cancer (See, claim interpretation). The method of treatment comprises added limitations for dependent claims to treat claimed mucosal cancer in immunocompromised subjects for different organs and systems mucosal surfaces.
State of the prior art: At the time the invention was made, it was known in the art that there is no availability of attenuated live HPV for treatment of mucosal cancers (See, instant specification).
Breadth of the claims: The claims are very broad, encompassing two genera (i) mucosal cancer, (ii) attenuated Human Papilloma Virus (HPV). (See, claim 1 interpretation below).
Working examples: No working examples are disclosed in the specification showing (i) treatment or reducing the risk to the subject from developing a non-HPV etiological mucosal cancer, (ii) an attenuated Human Papilloma Virus (HPV) for treatment of HPV etiological mucosal cancer or non-HPV etiological mucosal cancer.
Guidance in the specification: The specification of the published PGPub application (US20240100141A1, 03/28/2024) provides little guidance regarding making the composition and practice the claimed method. The specification recites Live Commensal HPV Vaccine Strategy in para [0033]. The applicant has incorporated by reference the published application WO 2020/112720.
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The specification of incorporated published WO 2020/112720 application (See, para [0057]- [0064]) does not show any working examples reduced to the practice for the genus (i) treatment or reducing the risk to the subject from developing a non-HPV etiological mucosal cancer, and the genus (ii) an attenuated Human Papilloma Virus (HPV) for treatment of HPV etiological mucosal cancer or non-HPV etiological mucosal cancer. Recited is a hypothesis of a research to develop or obtain an attenuated Human Papilloma Virus (HPV).
Predictability of the art: Based on the specification provided in the application and available prior art an unpredictable amount of research and efforts are required to arrive at the claimed full scope of inventions as per the independent claim and dependent claims thereon.
Amount of experimentation: In absence of recitation of working examples or reduction to practice (i) showing treatment or reducing the risk to the subject from developing a non-HPV etiological mucosal cancer, (ii) an attenuated Human Papilloma Virus (HPV) for treatment of HPV etiological mucosal cancer or non-HPV etiological mucosal cancer an undue amount of experimentation would be required to make and use the invention. Treatment or reducing the risk of a non-HPV etiological mucosal cancer is highly unpredictable. Attenuation of Human Papilloma Virus (HPV) that would not cause a mucosal cancer is highly unpredictable in the art.
Given the breadth of the claims, the lack of guidance in the specification, and the lack of predictability of the art, it would require an undue amount of experimentation for one skilled in the art to make and use the claimed invention and to reach to reduction to the practice to arrive at the instant claims 1-12 and 21-25.
Claim Interpretation
13. 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.
Claim 1: The instant claim 1 is directed to a method of treating, or reducing the risk of developing, mucosal cancer in a subject, the method comprising administering to the subject an effective amount of a composition comprising: a plurality of (i) antigenic peptides, each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses, or (ii) live or live-attenuated commensal human papilloma viruses; and a T cell adjuvant that increases T cell response to the antigenic peptides.
The broadest reasonable interpretation is that the claimed (i) antigenic peptides or (ii) live or live attenuated commensal HPVs of any or all serotypes/subtypes are administered in an effective amount to a subject to treat or reduce the risk of developing an HPV etiology mucosal cancer and as well as non-HPV etiology mucosal cancer. The mucosal cancer is interpreted to cancer of all mucosal surface of body (e.g. respiratory system, genital and urinal mucosa, skin, eye mucosal surface). The treatment is interpreted that the subject is already have a mucosal cancer. Reducing the risk is interpreted as reduction in possibility to develop a cancer but not prevention of a mucosal cancer.
Claim Rejections - 35 USC § 102
14. 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, 4-7 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Van Der Burg et al 2015 (US20150056234A1, 02/26/2015).
Van Der Burg et al 2015 is in the art and teaches a method of treatment of an HPV related disease (cervical cancer, mucosal cancer) comprising the administration of an effective amount of a peptide from having a length of no more than 100, 98, 96, 94 or 92 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of at least one of an HPV E6 and E7 protein, wherein the contiguous amino acid sequence comprises an epitope comprising novel CD4+ and CD8+ T cell epitopes that are specific for HPV specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions. T cell adjuvant, immune modifying compounds that are capable of activation of the innate immune system can be activated particularly well via Toll like receptors (TLR's), including TLR's 1-10, poly(I:C), are disclosed. Suitable viral expression constructs include e.g. vectors that are based on adenovirus, adeno-associated virus (AAV), retroviruses or modified vaccinia Ankara (MVA) are disclosed for nucleic acids encode two or more peptides and/or epitopes of the invention arranged as beads-on-string, whereby the peptides and/or epitopes of the invention (the beads) are linked directly together and/or are linked through linker sequences that are from proteins other than the wild type HPV E6 or E7 proteins and/or from other locations within the wild type HPV E6 or E7 proteins that are not contiguous with the peptide/epitope they flank. (See, claims 1-25, abstract, para [0003]-[0004], [0043], [0048], [0064], [0065], entire prior art).
A method for the prevention and/or treatment of an HPV related disease, wherein the peptide has a length of no more than 100 amino acids and comprises at least 19 contiguous amino acids from the amino acid sequence of at least one of an HPV E6 and E7 protein, wherein the contiguous amino acid sequence comprises an epitope that is recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node (See, claim 2).
It is implicit that plurality of antigenic peptides or epitopes are disclosed (See, claims 1-25, abstract, para [0003]-[0004], [0043], [0048], [0064], [0065], entire prior art).
Claim Rejections - 35 USC § 103
15. 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
16. Claims 1-11, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Van Der Burg et al 2015 (US20150056234A1, 02/26/2015), and further in view of Baker et al 2007 (US20070014810A1, 01/18/2007), Chen et al 2011 (Virology. 2010 Sep 30;405(2):289-99), Mailere et al 2004 (US7488791B2, 02/10/2009), Flynn et al 2011 (PNAS, 2011, vol 108 no.17, p. 7131-7136), Swaminathan et al 2016 (Vaccine, 34(1), 110-119), Zhao et al 2016 (PLoS pathogens, 16(9), e1008827), Daayana et al 2010 (British journal of cancer, 102(7), 1129-1136), Hancock et al 2018 (Best Practice & Research Clinical Obstetrics and Gynaecology 47 (2018) 59e72), Palefsky et al 2006 (Vaccine, 24, S140-S146), and Lauring et al 2010 (Nature biotechnology, 28(6), 573-579).
Claims 1, and 4-7: Van Der Burg et al 2015 is in the art and teaches a method of treatment of an HPV related disease (cervical cancer, mucosal cancer) comprising the administration of an effective amount of a peptide from having a length of no more than 100, 98, 96, 94 or 92 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of at least one of an HPV E6 and E7 protein, wherein the contiguous amino acid sequence comprises an epitope comprising novel CD4+ and CD8+ T cell epitopes that are specific for HPV specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions. T cell adjuvant, immune modifying compounds that are capable of activation of the innate immune system can be activated particularly well via Toll like receptors (TLR's), including TLR's 1-10, poly(I:C), are disclosed. Suitable viral expression constructs include e.g. vectors that are based on adenovirus, adeno-associated virus (AAV), retroviruses or modified vaccinia Ankara (MVA) are disclosed for nucleic acids encode two or more peptides and/or epitopes of the invention arranged as beads-on-string, whereby the peptides and/or epitopes of the invention (the beads) are linked directly together and/or are linked through linker sequences that are from proteins other than the wild type HPV E6 or E7 proteins and/or from other locations within the wild type HPV E6 or E7 proteins that are not contiguous with the peptide/epitope they flank. (See, claims 1-25, abstract, para [0003]-[0004], [0043], [0048], [0064], [0065], entire prior art).
Van Der Burg et al 2015 does not expressively teach plurality of antigenic peptides or epitopes.
Baker et al 2007 is in the art and teaches the mechanisms by which antigen is recognized by T cells to identify and prepare human papillomavirus (HPV) epitopes, and to develop epitope-based vaccines directed towards HPV, the invention also provides multi-epitope nucleic acid constructs encoding a plurality of CTL and/or HTL epitopes and methods inducing an immune response against human papillomavirus virus (HPV) in an individual in need thereof. Instant claims 6-7 limitations on sequences of the HPV peptides or epitopes (including nucleotide sequences encoding peptides) with unique sequences are disclosed (See, abstract, claims 1-22, para [0043]).
Both Van Der Burg et al 2015 and Baker et al 2007 does not teach live-attenuated commensal HPVs or live HPV as a vaccine.
Chen et al 2011 is in the recombinant HPV production art and teaches using the HPV18 genome as the backbone for inter-typical exchange of HPV18 L1 with the HPV16 L1 genomes that efficiently replicated and produced infectious virus. Using chimeric constructs of individual capsid proteins, we identified a type specific domain at the N-terminus of the HPV18L1 capsid protein, which interferes with its ability to cooperate with the HPV16 L2 protein to form infectious viral particles. Deletion of this domain allows for the cooperation of the HPV18 L1 protein and HPV 16 L2 protein and production of infectious progeny. Additionally, cooperation of this N-terminal HPV18 L1 deletion mutant protein with the wild type HPV18 L2 protein efficiently replicates infectious virus but changes occur in the viral structure. Therefore, the teachings of Chen et al 2011 are applicable to produce attenuated HPV virus by introducing desired mutations in pathogenic or virulence markers for attenuation to use as a live vaccine (See, abstract, entire article).
Lauring et al 2010 is in the art and teaches Zinc-finger nuclease-controlled live attenuated virus development that is applicable for human papilloma virus (See, page 576 col2 last para, page 577-578, Table 2 last row Human Papilloma virus (experimental).
Therefore, the teachings of Chen et al 2011 and Lauring et al 2010 are applicable to reasonably develop attenuated HPV virus based on molecular attenuation methods and render obvious the claim 1 limitation live or live-attenuated commensal human papilloma viruses.
Claims 2-3: Van Der Burg et al 2015, Baker et al 2007, and Chen et al 2011 does not teach low risk HPVs.
Mailere et al 2004 is in the art and teaches a mixture of peptides derived from HPV E6 and/or E7 proteins of a papillomavirus involved in cervix of uterus cancer, such as HPV16, HPV18, HPV30, HPV31, HPV32, HPV33, HPV34, HPV35, HPV39, HPV40, HPV42, HPV43, HPV44, HPV45, HPV51, HPV52, HPV56, HPV57, and HPV58, for example, as well as its uses as medicine (in immunogenic compositions, capable of stimulating the production of anti-HPV T CD4+ lymphocytes in vivo and hence useful for vaccination against uterine of uterus cancer and in other cancers (see, abstract).
Mailere et al 2004 teaches the instant claims 2 and 3 added limitation as below:
Claim 2. The method of claim 1, wherein the commensal human papilloma viruses are low risk a-HPV, P-HPV, y-HPV, and/or p-HPV strains. The low risk HPV strains are disclosed (See, Mailere et al 2004 para [0005]).
Claim 3. The method of claim 1, wherein the commensal human papilloma viruses are P-HPV and/or y-HPV strains listed in Table A. The low risk HPV strains are disclosed (See, Mailere et al 2004 para [0005]).
Claim 8: Van Der Burg et al 2015 teaches instant claim 8 added limitation, wherein the T cell adjuvant comprises one or more of nanoparticles that enhance T cell response; poly-ICLC (carboxymethylcellulose, polyinosinic- FH13322200.1 polycytidylic acid, and poly-L-lysine double-stranded RNA), Imiquimods, CpG (see, para [0048]), ligodeoxynuceotides and formulations (IC31, QB10), ASO4 (aluminium salt formulated with 3-O-desacyl-4'-monophosphoryl lipid A (MPL)), ASO1 (MPL and the saponin QS-21), MPLA,'TING agonists, other TLR agonists (see, para [0048]), Candida albicans Skin Test Antigen (Candin), GM-CSF,Fms-like tyrosine kinase-3 ligand (Flt3L), and/or IFA Incomplete Freund's adjuvant [0060]).
Flynn et al 2011 is in the vaccine art and teaches poly-ICLC adjuvant for HIV-Gag vaccine and disclosed that poly ICLC was essential for T- and B-cell immunity. (See, abstract).
Van Der Burg et al 2015 and Flynn et al 2011 does not teach T cell adjuvant comprised in nanoparticle.
Swaminathan et al 2016 is in the art and teaches a novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens (See, abstract, entire article).
Zhao et al 2016 is in the art and teaches combined prophylactic and therapeutic immune responses against human papillomaviruses induced by a thioredoxin-based L2-E7 nanoparticle vaccine (See, abstract, entire article).
The nanoparticle formulation would enhance T cell immune response as taught by Swaminathan et al 2016 and Zhao et al 2016.
Claim 9. Mailere et al 2004 does not teach claim 9 added limitation, wherein the T cell adjuvant comprises topical imiquimod.
Daayana et al 2010 is in the HPV therapeutic vaccine art and teaches added limitation of the instant claim 9, wherein the T cell adjuvant comprises topical imiquimod or topical 5-fluorouracil. Clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. (See, Daayana et al 2010, abstract, entire article).
Claims 10 and 23: Palefsky et al 2006 is in the art directed to HPV vaccines in immunocompromised women and men and teaches added limitation of the instant claims 10 and 23, wherein the subject has an increased risk of developing mucosal cancer or is immunocompromised by disclosing Oral HPV infection and oral cancer in HIV-positive and other immunocompromised men and women oral HPV infection is thought to be a potential etiologic agent for only a subset of head and neck squamous-cell carcinomas HNSCCs. (See, Palefsky et al 2006, page S3/142 col 2 section 4.0 and 4.1).
Claim 11: Hancock et al 2018 is in the art and added limitation of instant claim 11 by disclosing HPV peptide vaccine as well as viral vector-based HPV vaccine as therapeutic HPV vaccines. Hancock et al 2018 teaches persistent hrHPV infections and preinvasive lesions are significantly more frequent in immunosuppressed states such as untreated HIV infection or receipt of antirejection therapy post-transplant and thus renders obvious the limitation, wherein the subject is immunocompromised as a result of an acquired immunodeficiency or an organ transplant. (See, Hancock et al 2018, page 61 lines 6-8).
Claim 24: Van Der Burg et al 2015 teaches added limitation of instant claim 24, wherein the mucosal cancer is a mucosal squamous cell carcinoma (mSCC); a head and neck cancer (HNC); a cancer of the mucosa of the upper respiratory tract; or a cancer of the genitourinary tract. (See, Van Der Burg et al 2015 para [0042], [0055], [0066]).
Claim 25: Van Der Burg et al 2015 teach the added limitation of claim 25, wherein the mucosal cancer is an anal cancer, a cervical cancer,or a cancer of the vulva, the vestibule, the vagina, the perineum, or the perianal tissue. (See, Van Der Burg et al 2015 para [0042], [0055], [0066]).
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 prior art teachings of Van Der Burg et al 2015 with additional teachings of Baker et al 2007, Chen et al 2011, Lauring et al 2010, Mailere et al 2004, Flynn et al 2011, Swaminathan et al 2016 and Zhao et al 2016, Daayana et al 2010, Hancock et al 2018, and Palefsky et al 2006 as recited supra to develop method of treatment of HPV in a subject to arrive at the invention of instant claims 1-11 and 23-25. One of ordinary skills in the art would have been motivated to develop the methods for reducing the risk of developing a mucosal cancer in a subject and for commercial advantage and success. One of the ordinary skills would have been apprised of a reasonable expectation of success to arrive at the invention of claims 1-11 and 23-25 given the combined prior art teachings as applied and as recited supra and render obvious the claimed invention. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention of instant claims 1-11 and 23-25. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
Double Patenting
17. 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 1-11 and 23-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-8, 12, 16-22, and 26-27 of copending Application No. 17/296,829 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the copending claims and instant claims are directed to “A method of treating, or reducing the risk of developing, mucosal cancer in a subject, the method comprising administering to the subject an effective amount of a composition comprising: a plurality of (i) antigenic peptides, each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses, or (ii) live or live-attenuated commensal human papilloma viruses; and a T cell adjuvant that increases T cell response to the antigenic peptides”.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Relevant Prior Arts:
Schiller et al 2015. Next generation prophylactic human papillomavirus vaccines. The lancet oncology, 16(5), e217-e225.
Dadar et al 2018. Advances in Designing and Developing Vaccines, Drugs and Therapeutic Approaches to Counter Human Papilloma Virus. Front Immunol. 2018 Nov 12;9:2478.
Brimer et al 2017. Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness. PLoS pathogens, 13(12), e1006781.
Conclusion
18. No claim is allowed.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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/SAMADHAN JAISING JADHAO/ Examiner, Art Unit 1672
/BENNETT M CELSA/ Primary Examiner , Art Unit 1600
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