DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
In the Preliminary Amendment filed 21 June 2024, Applicant amended claims 1-57, 62, and 70-73. Additionally, Applicant added one new claim (claim 74) and cancelled claims 58-61 and 63-69. Claims 1-57, 62, and 70-74 are pending.
Claim Objections
Claims 9-11 are each objected to because of the following informality: There is no period at the end of the claim. Appropriate corrected is required.
Claim Rejections - 35 U.S.C. 112(a)
The following is a quotation of 35 U.S.C. 112(a):
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.
Claims 71-74 are rejected under 35 U.S.C. 112(a) for lack of enablement.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics, 8 USPQ2d 1217 (Fed. Cir. 1988)). MPEP § 2164.01. Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. MPEP § 2164.01(a). These factors were outlined in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988) and include the following: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of any working examples; and (8) the quantity of experimentation necessary needed to practice the claimed invention based on the content of the disclosure. MPEP § 2164.01(a).
There is no requirement in claims 71-74 that an effective amount of the HPV E6/E7-antigen-encoding mRNA/cationic lipid particles (as defined in claim 1) or the composition incorporating them (as defined in claim 62) is administered to the mammal. Applicant’s specification does not reasonably provide enablement for treating/preventing an HPV infection, for inducing an immune reaction, or for expressing E6/E7 antigens by administering a negligible or otherwise ineffective amount of the foregoing particles or composition to a mammal. In sum, a person having ordinary skill in the art could not practice the full scope of Applicant’s invention, as recited in claims 71-74, without first engaging in undue experimentation.
Claim Rejections - 35 U.S.C. 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 1-31, 39, 47, 53-57, 62, and 70-74 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella (US 2018/0296662 A1) in view of Koizumi (US 9,803,199 B2).
Ciaramella is directed to vaccines for sexually transmitted diseases. Title/Abstract.
Ciaramella discloses: “A human papillomavirus (HPV) vaccine, comprising: a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding a HPV antigenic polypeptide formulated in a lipid nanoparticle that comprises a molar ratio of 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic lipid.” Claim 3 (emphasis added).
Ciaramella discloses: “In some embodiments, the at least one antigenic polypeptide is E6, E7, or a combination of E6 and E7.” Para. [0018] (emphasis added); see also para. [0024] (“In some embodiments a vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one polypeptide selected from E6 and E7 protein obtained from HPV, or a combination thereof.”).
Ciaramella discloses that a single RNA polynucleotide can encode two antigenic polypeptides selected from HPV E1 protein, HPV E2 protein, HPV E4 protein, HPV E5 protein, HPV E6 protein, HPV E7 protein, HPV L1 protein, and HPV L2 protein. Claim 5 at section (a); see also para. [0212] (“The present disclosure encompasses STD vaccines comprising multiple RNA (e.g., mRNA) polynucleotides, each encoding a single antigenic polypeptide, as well as STD vaccines comprising a single RNA polynucleotide encoding more than one antigenic polypeptide (e.g., as a fusion polypeptide).”).
On the basis of the foregoing disclosure, a person having ordinary skill in the art would have readily envisaged a single RNA polynucleotide that encodes both an HPV E6 antigenic polypeptide and an HPV E7 antigenic polypeptide. MPEP § 2131.02(III) (“A reference disclosure can anticipate a claim when the reference describes the limitations but ‘d[oes] not expressly spell out’ the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination.”), quoting Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2015).
Although Ciaramella discloses that the nanoparticle comprises a cationic lipid (claim 3) and identifies various exemplary cationic lipid compounds (paras. [0357] and [0562]-[0569]), none of those cationic lipids satisfies Formula (Ia) of claim 1 of the present application. As explained below, Koizumi compensates for this deficiency.
Koizumi is directed to a cationic lipid that forms a lipid particle. Title/Abstract.
Koizumi teaches: “[T]he present inventors have completed the present invention by finding a novel cationic lipid and further finding a nucleic acid lipid particle comprising the novel cationic lipid that can encapsulate therein a nucleic acid molecule, can be used at a low concentration, and permits a high level of delivery into cells.” Column 1, line 66, to column 2, line 5 (emphasis added).
Koizumi teaches: The term “nucleic acid” includes a messenger RNA (mRNA). Column 65, lines 5-8. “The nucleic acid contained in the nucleic acid lipid particle can be any single-stranded RNA without particular limitations and also includes mRNA that is translated into a protein.” Column 92, lines 25-28 (emphasis added).
Koizumi teaches: “The single-stranded RNA is used for treating a disease or supplying a beneficiary protein. The single-stranded RNA is delivered to an organ responsible for the disease through the nucleic acid lipid particle of the present invention and further transported into the cytoplasm. When the single stranded RNA encodes a protein, the single-stranded RNA is translated into the protein in the cytoplasm so that this protein brings about the curing of the disease.” Column 93, lines 27-35.
Claim 1 of Koizumi is reproduced below:
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The examiner notes that the cationic lipid set forth in claim 1 of Koizumi matches the cationic lipid set forth in claim 9 of the present application.
Additionally, the exemplary cationic lipid taught in Formula 4 of Kiozumi (columns 7-8), which is set forth below, matches the cationic lipid set forth in claim 10 of the present application.
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Similarly, the exemplary cationic lipid taught in Formula 11 of Kiozumi (columns 9-10), which is set forth below, matches the cationic lipid set forth in claim 10 of the present application.
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817
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Before the effective filing date of the claimed invention, the foregoing teachings would have motivated a person having ordinary skill in the art to include the cationic lipid of claim 1 of Koizumi in the lipid nanoparticle of Ciaramella, in an effort to enhance the cellular delivery of the E6/E7-antigen-encoding mRNA into the cytoplasm following administration and, thereby, potentially increase the effectiveness of the HPV vaccine. In the course of routine experimentation, the person having ordinary skill in the art would have also tested the compounds of Formulas 4 and 11 of Koizumi to determine whether either of them facilitated delivery into the cytoplasm when included in the lipid nanoparticle of Ciaramella. Therefore, claims 1-11 are prima facie obvious.
Regarding claims 12-17, Applicant is referred to Ciaramella at (i) claim 3 (quoted above) and claim 54 and (ii) paragraphs [0062] and [0075]. Ciaramella further discloses that the non-cationic lipid can be a neutral lipid, such as DSPC (distearoyl phosphatidylcholine), DPPC, POPC, DOPE (dioleoyl phosphatidylethanolamine), and SM. Paras. [0305], [0307], and [0334]. The examiner notes that the neutral lipid of Ciaramella corresponds to the “amphipathic lipid” of the present claims.
Regarding claims 18-19, Applicant is referred to paragraph [0302] of Ciaramella.
Regarding claims 20-27, Applicant is referred to Ciaramella at claim 3 (quoted above) and paragraph [0307]. MPEP § 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”). Additionally, Applicant is alerted that “‘[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.’” MPEP § 2144.05(II)(A), quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955). Again, the neutral lipid of Ciaramella corresponds to the “amphipathic lipid” of the present claims.
Regarding claims 28-30, Ciaramella discloses: “In some embodiments, the ratio of lipid to RNA (e.g., mRNA) in lipid nanoparticles may be 5:1 to 20:1, 10:1 to 25:1, 15:1 to 30:1 and/or at least 30:1.” Para. [0302]. Applicant is referred to MPEP § 2144.05(I) (quoted above).
Regarding claims 31, 39 and 47, Ciaramella discloses HPV serotypes 6 and 11 in claim 4.
Regarding claims 53-56, Applicant is referred to claims 36-39 of Ciaramella.
Regarding claim 57, Ciaramella discloses: “In some embodiments, a nanoparticle (e.g., a lipid nanoparticle) has a mean diameter of 10-500 nm, 20-400 nm, 30-300 nm, 40-200 nm. In some embodiments, a nanoparticle (e.g., a lipid nanoparticle) has a mean diameter of 50-150 nm, 50-200 nm, 80-100 nm or 80-200 nm.” Para. [0325]. Applicant is referred to MPEP § 2144.05(I) (quoted above).
Regarding claim 62, Applicant is referred to paragraph [0292] of Ciaramella, which discloses “traditional excipients such as any and all solvents, dispersion media, diluents, or other liquid vehicles.” See also para. [0324] (water for injection).
Regarding claim 70, Applicant is referred to paragraph [0278] of Ciaramella, which discloses: “The STD RNA (e.g., mRNA) vaccines may be induced for translation of a polypeptide (e.g., antigen or immunogen) in a cell, tissue or organism. In some embodiments, such translation occurs in vivo, although such translation may occur ex vivo, in culture or in vitro.”
Regarding claim 71, Applicant is referred to paragraph [0277] of Ciaramella, which discloses: “In some embodiments, STD vaccine containing RNA (e.g. mRNA) polynucleotides as described herein can be administered to a subject (e.g., a mammalian subject, such as a human subject), and the RNA (e.g., mRNA) polynucleotides are translated in vivo to produce an antigenic polypeptide.”
Regarding claim 72, Applicant is referred to Ciaramella at claim 66 and at paragraphs [0007], [0090], and [0134].
Regarding claim 73, Applicant is referred to Ciaramella at claim 66 and at paragraphs [0008], [0263], and [0276].
Regarding claim 74, Applicant is referred to paragraph [0103] of Ciaramella. See also para. [0263] (“It is possible, although less desirable, to administer the vaccine to an infected individual to achieve a therapeutic response”). A person having ordinary skill in the art would have readily recognized that an individual infected with HPV, especially serotypes 6 or 11, is at risk of developing condyloma acuminata (anogenital warts).
Claims 32-35, 37, 40-43, 45, 49, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella (US 2018/0296662 A1) in view of Koizumi (US 9,803,199 B2), as applied above to claims 1-31, 39, 47, 53-57, 62 and 70-74, and further in view of Weiner (US 9,505,287 B2) and/or Ramos (US 2021/0353736 A1).
Neither Ciaramella nor Koizumi discloses sequences that are at least substantially similar to SEQ ID Nos: 12-15 and 17-18 of the present application. Consequently, the combination of Ciaramella and Koizumi does not satisfy claims 32-34 and 40-42.
Furthermore, although Ciaramella discloses a 5’-cap, a 5’-UTR, a leader sequence, an open reading frame, a 3’-UTR, and a 3’-poly(A) tail (paras. [0216], [0242], [0252], and [0293]-[0294]), Ciaramella is silent as to whether the mRNA can further comprise a furin cleavage site, as is Koizumi. Consequently, the combination of Ciaramella and Koizumi does not satisfy claims 35, 37, 43, 45, 49, and 51.
As explained below, Weiner and/or Ramos compensate for the foregoing deficiencies.
Weiner is directed to vaccines for HPV.
Weiner teaches “various studies have revealed the presence of HPV6 and HPV11 in most incidences of recurrent respiratory papillomatosis” and are “known for their association with genital warts.” Column 1, lines 34-36.
Weiner teaches improved anti-HPV immunogens and nucleic acid molecules that encode them, including immunogens having consensus E6/E7 for HPV serotypes 6 and 11. Abstract. Among those immunogens are SEQ ID NO: 2 (an HPV6 E6E7 protein sequence) and SEQ ID NO: 4 (an HPV11 E6/E7 protein sequence). Weiner at columns 21-24.
The examiner notes that SEQ ID NO: 2 of Weiner is (i) a 97.8% match to Applicant’s SEQ ID NO: 12, (ii) a 94.3% match to Applicant’s SEQ ID NO: 13, and (iii) a 96.5% match to Applicant’s SEQ ID NO: 17.
Similarly, SEQ ID NO: 4 of Weiner is (i) a 97.8% match to Applicant’s SEQ ID NO: 14, (ii) a 95.0% match to Applicant’s SEQ ID NO: 15, and (iii) a 96.8% match to Applicant’s SEQ ID NO: 18.
Ramos is directed to “vaccines for recurrent respiratory papillomatosis and methods of using the same.” Title.
Ramos teaches: “Provided herein are nucleic acid molecules encoding a human papillomavirus (HPV) antigen, the HPV antigen comprising a HPV6 antigenic domain and a HPV11 antigenic domain. In some embodiments, the HPV6 antigenic domain comprises a HPV6 E6 antigenic domain and a HPV6 E7 antigenic domain. In some embodiments, the HPV11 antigenic domain comprises a HPV11 E6 antigenic domain and a HPV11 E7 antigenic domain. The nucleic acid molecules provided herein may encode a HPV antigen comprising: the amino acid sequence of SEQ ID NO:1 or SEQ ID NO: 11; an amino acid sequence that is at least 95% homologous to SEQ ID NO:1 or SEQ ID NO: 11; a fragment of 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 a fragment of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO: 11.” Para. [0006].
SEQ ID NO: 1 of Ramos (pages 32-34) is (i) a 95.4% match to Applicant’s SEQ ID NO: 12, (ii) a 95.6% match to Applicant’s SEQ ID NO: 13, (iii) a 94.1% match to Applicant’s SEQ ID NO: 17, (iv) a 95.3% match to Applicant’s SEQ ID NO: 14, and (v) a 93.8% match to Applicant’s SEQ ID NO: 18.
SEQ ID NO: 11 of Ramos (pages 43-44) is a 95.0% match to Applicant’s SEQ ID NO: 15.
Additionally, Ramos teaches the incorporation of furin cleavage sites to assist in post-translational optimization. Paras. [0021], [0090], [0096], [0269], and [0274]; see also Figure 1A (showing furin/P2A cleavage sites).
Before the effective filing date of the claimed invention, a person having ordinary skill in the art would have been motivated to modify the lipid nanoparticle of Ciaramella by including therein an mRNA encoding for the E6/E7 antigens (HPV6+HPV11) taught in Weiner or Ramos for the purpose of formulating an HPV vaccine that is more effective in preventing recurrent respiratory papillomatosis (RRP) or anogenital warts. Following the teachings of Ramos, the person having ordinary skill in the art would have included a furin cleavage site in the mRNA (which is polycistronic) to ensure that the E6 and E7 antigens do not remain bound to one another in vivo; otherwise, it would be difficult for those antigens to achieve their respective immunologically-active conformations. Therefore, claims 32-35, 37, 40-43, 45, 49, and 51 are prima facie obvious.
Claim Rejections - Double Patenting (Non-Statutory)
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 obviousness-type 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR1.321(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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 eTerminalDisclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/ eTD-info-I.jsp.
Claims 1-35, 37, 39-43, 45, 47, 49, 51, 53-57, 62, and 70-74 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 12, 14, 16, 18, 20-24, 27-45, 48, 50, 53-57, 70, and 72 of co-pending Application No. 17/776,743 (as amended on 11 December 2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: Conflicting claim 1 of the ’743 Application is directed to a lipid particle encapsulating a nucleic acid molecule capable of expressing the E6 and E7 antigens of human papillomavirus (HPV). The lipid particle of conflicting claim 1 further comprises the same cationic lipid that is set forth in claim 9 of the present application. The examiner acknowledges that the amino acid sequences (E6/E7 antigens) of conflicting claim 1 are directed to the HPV16 and HPV18 serotypes, whereas present claim 1 is generic as to serotype. In the interest of clarity, the examiner notes there is limited structural similarity between those sequences and the sequences introduced in several of the dependent claims of the present application (i.e., claims 36, 38, 44, 46, 48, 50, and 52), which are specifically directed to the HPV6 and HPV11 serotypes. In sum, present claims 1-35, 37, 39-43, 45, 47, 49, 51, 53-57, 62, and 70-74 are not patentably distinguishable over the conflicting claims of the ’743 Application.
This is a provisional rejection because the conflicting claims have not been patented.
Allowable Subject Matter
Claims 36, 38, 44, 46, 48, 50, and 52 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Referring to claims 36 and 38, SEQ ID NO: 5 is both novel and non-obvious. SEQ ID NO: 1 of Weiner (US 9,505,287 B2), which is representative of the closest prior art, has a sequence similarity of 68.6%.
Referring to claims 44 and 46, SEQ ID NO: 8 is both novel and non-obvious. SEQ ID NO: 3 of Weiner (US 9,505,287 B2), which is representative of the closest prior art, has a sequence similarity of 68.4%.
Referring to claim 48, SEQ ID NO: 19 is both novel and non-obvious. SEQ ID NOs: 1 and 11 of Ramos (US 2021/0353736 A1), which are representative of the closest prior art, have a sequence similarity of 78.5%.
Referring to claims 50 and 52, SEQ ID NO: 11 is both novel and non-obvious. SEQ ID NO: 3 of Ramos (US 2021/0353736 A1), which is representative of the closest prior art, has a sequence similarity of 43.7%.
Additional detail is forth in the Automated Biotechnology Sequence Search (ABSS) search results dated 3/20/2026 and 3/21/2026, which have been included in the electronic file history of this application and are accessible via Patent Center.
Applicant is encouraged to focus claim 1 on the allowable subject matter identified above.
Conclusion
Claims 1-35, 37, 39-43, 45, 47, 49, 51, 53-57, 62, and 70-74 are rejected.
Claims 9-11, 36, 38, 44, 46, 48, 50, and 52 are objected to.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
03 April 2026
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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