DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Notice Regarding Allowable Subject Matter
In the non-final Office Action, mailed on 11 September 2025, Applicant was notified that pending claims 32, 34, and 70 would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims because the prior art is free of nucleic acids capable of expressing a protein with an amino acid sequence with ≥95% identity with SEQ ID NO: 17 and nucleic acids with sequences that have ≥90% identity with SEQ ID NO: 2, 4, or 6. A telephone call was made to Richard L. Green, Ph.D., J.D., on 12 February 2026, and 3 March 2026, to discuss the potentially allowable subject matter and response to the previous Office Action. However, the Examiner was unable to reach Richard L. Green, Ph.D., J.D., necessitating the following Office Action.
Response to Amendments
Status of Claims
The amendment, filed on 11 December 2025, is acknowledged.
Claims 1, 12, 14, 18, 20-24, 27-45, 48, 70, and 72 are amended.
Claims 69 and 71 are cancelled.
Claims 35-40, 53-57, and 72 were previously withdrawn from consideration in the non-final Office Action mailed on 11 September 2025.
Claims 1, 12, 14, 16, 18, 20-24, 27-34, 41-45, 48, 50, and 70 are pending and under consideration in the instant Office Action to the extent of the following previously elected species:
the specific cationic lipid R1=R2=methyl, L1=(S,E)-heptadec-9-en-7-yl acetate, L2=(R,E)-heptadec-9-en-7-yl acetate, and p=3, as in claim 9;
the specific nucleic acid molecule is a nucleic acid molecule that encodes SEQ ID NO: 17, as in claim 32;
the specific human papillomavirus HPV16;
the specific amphipathic lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC);
the specific sterol cholesterol; and
the specific PEG lipid 1,2-dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG).
Objections Withdrawn
Objections to Claims
Applicant’s amendments to claims 1, 12, 14, 16, 18, 20-24, 27-34, 41-45, 48, and 70, submitted on 11 December 2025, have overcome the objection to the claims set forth in the Office Action mailed on 11 September 2025. Accordingly, the relevant objections are withdrawn.
Rejections Withdrawn
Rejections pursuant to 35 U.S.C. § 112
The rejection of claims 12, 14, 16, 18, 20-24, 27-28 under 35 U.S.C. § 112 is withdrawn in view of Applicant’s amendments to the claims.
Rejections pursuant to 35 U.S.C. § 103
The rejection of claims 1, 12, 14, 16, 18, 20-24, 27-34, 41-45, 48, 50, and 70 under 35 U.S.C. § 103 is withdrawn in view of Applicant’s amendments to the claims and in favor of the new grounds of rejection below. The rejection of claim 69 under 35 U.S.C. § 103 has been rendered moot in view of Applicant’s cancellation of the claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 13 May 2022, cited Schiller, J. “Human papilloma virus vaccines”, Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy, (2003), 43:528 (Abstract) as Citation No. 1 under the section Non-Patent Literature Documents. The citation was erroneously lined through in the non-final Office Action mailed on 11 September 2025.
The relevant citation on the IDS, filed on 13 May 2022, is being considered by the examiner and a corrected IDS has been included in the instant Office Action.
New Grounds of Rejection
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.
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.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Daiichi Sankyo Co., LTD. (WIPO International Patent Publication No. WO 2015/005253 A1, published on 15 January 2015, cited on IDS filed 13 May 2022, references to English translation) in view of Orlinger et al. (WIPO International Patent Publication No. WO 2016/198531 A2, published on 15 December 2016, hereafter referred to as Orlinger) and Yan et al. (Mol. Therapy 2007, 15 (1), 411., hereafter referred to as Yan).
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Daiichi teaches a cationic lipid of formula (Ia)
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and lipid particles which may contain the above cationic lipid along with nucleic acids, drugs, and other active ingredients, as well as a pharmaceutical composition and a treatment method comprising the lipid particles (Abstract, Description para. 1, and claim 1). In one embodiment, the cationic lipid of formula (Ia) possesses R1=R2=methyl, R8=H, L1=(S,E)-heptadec-9-en-7-yl acetate, L2=(R,E)-heptadec-9-en-7-yl acetate, p=r=1, and m=0 (claims 1 and 26). The cationic lipid in claim 26 has the structure
which is identical to the cationic lipid recited in instant claim 1.
Daiichi further teaches lipid particles containing the cationic lipid above, in addition to containing a lipid that reduces aggregation during formation of the lipid particle (claims 33-34). The lipid that reduces aggregation during formation is preferably a polyethylene glycol (PEG) lipid and in one embodiment is PEG-DMG (claims 35-36). The lipid particles are further taught to comprise cholesterol (claim 45) and an amphipathic lipid, which in one embodiment is DSPC (claims 46-47). The lipid particle is taught to have a total lipid composition that is, in molar amounts, ≤25% amphiphilic lipids, ≥15% sterols, 20-70% cationic lipids, and 1-10% lipid that reduces aggregation, which is preferably a PEG lipid (claim 49). The lipid particles are further taught to have an “average particle diameter of about 30 nm to about 300 nm” (claim 57).
Daiichi also teaches the lipid particles of their invention to comprise nucleic acids, which may be single- or double-stranded, contain DNA or RNA alone or in a mixture, or multiple types of nucleic acids (claims 51-52). The quantity of lipids to nucleic acids is taught to be in a wide range, with the total polynucleotide weight/total lipid weight spanning from 0.037 (Table 24) to 0.160 (Table 11). This range is equivalent to a range of total lipid weight to total nucleic acid weight ratios of 6.25 to 27.03, which significantly overlaps with the ratios recited in instant claims 20, 23, and 27-28. The nucleic acid containing lipid particles may also be part of a pharmaceutical composition (pg. 10, para. 7). The pharmaceutical composition may be used in a method for treating a disease, such as cervix cancer, and the lipid particles may be administered alone or with a pharmaceutically acceptable carrier (pg. 10, para. 7 and pg. 48, section 4, para.1-4)
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the quantities of lipids in the lipid particles recited in instant claims 20-25, the ratios of total lipid weight to total nucleic acid weight, and the diameter of the lipid particles. In each case, the prior art teaches a range that either significantly overlaps with or encompasses the ranges recited in the instant application.
Finally, Daiichi teaches the nucleic acid of their invention to comprise both natural and chemically modified nucleosides/nucleotides (pg. 39, section 3-2, para. 1). Examples of modified nucleosides/nucleotides a include 5-methylcytidine (pg. 39, section 3-2, para. 2) and a 5’-substituted pseudouridine (pg. 47, section 3-4-3.1, para. 3). The nucleic acid molecule is also taught in some embodiments to be mRNA which can contain a cap structure, untranslated regions at the 3’ and/or 5’ end, and/or a polyA tail (pg. 47, section 3-4-3.1, para. 1).
Daiichi does not teach the encapsulated nucleic acid molecule to be an mRNA molecule with a protease cleavage sequence (furin cleavage site) and coding region of a leader sequence nor to be capable of expressing E6 and E7 antigens of HPV16, where the E6 antigen has ≥95% identity with SEQ ID No. 8 and the E7 antigen has ≥95% identity with SEQ ID No. 9. These deficiencies are offset by the teachings of Orlinger and Yan.
Orlinger teaches pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions associated with human papillomavirus (HPV) infection, such as cervical, anogenital, and skin cancers (Abstract and para. [0002]). HPV is taught to be associated with cancer, in particular HPV types 16, 18, 31, and 45, because they have been found to in a high risk of the infected developing cancer (para. [0004-0005]). HPV16 and HPV18 are taught account for 70% of cervical cancers, a type of cancer that is the second most lethal to women worldwide (para. [0005-0006]). Traditional cancer treatment methods for cervical cancer produce “significant unwanted side effects” and can still leave patients with poor prognoses, demonstrating the need for new treatment methods that specifically target cancerous cells and/or clear HPV infections in patients to reduce the impact of HPV infection and possible prevent related cancers (para. [0007-0008]).
Two FDA and EMA approved HPV vaccines are available and help prevent HPV infection, but Orlinger teaches that they are not capable of altering the course of existing HPV infections (para. [0009]). One method of treatment taught by Orlinger is regulation of “HPV early proteins”, E1-E7, and in particular regulation of E6 and E7 which “are known to act as oncogenes that promote tumor growth and malignant transformation” (para. [0010]). These proteins can be regulated via the administration of an infectious, replication-deficient arenavirus viral vector that comprises a nucleotide sequence that is capable of encoding one or more HPV antigens (claims 3 and 6, para. [0019-0022]). The nucleotide sequence can encode one or more HPV antigens for one type of HPV or can have one or more antigens for one or more type of HPV, such as an E6 antigen for HPV16 and an E7 antigen for HPV18 (claims 9-12 and para. [0023-0026]). The amino acid sequence encoded by the aforementioned nucleotide sequence may also contain a furin cleavage site separating two or more HPV antigens (para. [00410]).
In one embodiment, the nucleotide sequence encodes an HPV16 E7/E6 fusion protein that is 100% identical to SEQ ID NO: 10 (para. [0052] and claim 52). The nucleotide molecule is taught to have the sequence SEQ ID NO: 14 (para. [00163]). The protein represented by SEQ ID NO: 10 of Orlinger is an amino acid sequence of a “HPV16 E7/E6 fusion protein with mutations in Rb [retinoblastoma] binding site and zinc finger motifs” (para. [00159]). SEQ ID NO: 10 of Orlinger contains an HPV16 E6 antigen that has 97.3% identity with instant SEQ ID NO: 8 and an HPV16 E7 antigen that has 100% identity with instant SEQ ID NO: 9 (claims 35, 52, 124, 128, 205, and 233 and para. [0048]).
CC PN WO2016198531-A2.
XX
CC PD 15-DEC-2016.
XX
CC PF 09-JUN-2016; 2016WO-EP063182.
XX
PR 10-JUN-2015; 2015US-0173805P.
PR 12-NOV-2015; 2015US-0254410P.
PR 03-MAY-2016; 2016US-0331158P.
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CC PA (HOOK-) HOOKIPA BIOTECH AG.
XX
CC PI Orlinger K, Monath T, Lilja A, Schmidt S, Berka U;
CC PI Schwendinger M, Watson E, Kiefmann B, Hinteramskogler J, Fuhrmann G;
CC PI Aspock A, Cohen K;
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CC PS Claim 35; SEQ ID NO 10; 270pp; English.
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SQ Sequence 255 AA;
Query Match 95.0%; Score 795; Length 255;
Best Local Similarity 97.3%;
Matches 146; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 1 FQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIVYRDGNPYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 106 FQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIVYRDGNPYA 165
Qy 61 VCDKGLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPEEKQRHLDK 120
| || ||||||||||||||||||||||||||||||||||||||| |||||||||||||||
Db 166 VGDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINGQKPLCPEEKQRHLDK 225
Qy 121 KQRFHNIRGRWTGRGMSCCRSSRTRRETQL 150
|||||||||||||| |||||||||||||||
Db 226 KQRFHNIRGRWTGRCMSCCRSSRTRRETQL 255
CC PN WO2016198531-A2.
XX
CC PD 15-DEC-2016.
XX
CC PF 09-JUN-2016; 2016WO-EP063182.
XX
PR 10-JUN-2015; 2015US-0173805P.
PR 12-NOV-2015; 2015US-0254410P.
PR 03-MAY-2016; 2016US-0331158P.
XX
CC PA (HOOK-) HOOKIPA BIOTECH AG.
XX
CC PI Orlinger K, Monath T, Lilja A, Schmidt S, Berka U;
CC PI Schwendinger M, Watson E, Kiefmann B, Hinteramskogler J, Fuhrmann G;
CC PI Aspock A, Cohen K;
XX
CC PS Claim 35; SEQ ID NO 10; 270pp; English.
XX
SQ Sequence 255 AA;
Query Match 100.0%; Score 530; Length 255;
Best Local Similarity 100.0%;
Matches 97; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HGDTPTLHEYMLDLQPETTDLYGYGQLNDSSEEEDEIDGPAGQAEPDRAHYNIVTFCCKC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 HGDTPTLHEYMLDLQPETTDLYGYGQLNDSSEEEDEIDGPAGQAEPDRAHYNIVTFCCKC 61
Qy 61 DSTLRLCVQSTHVDIRTLEDLLMGTLGIVGPICSQKP 97
|||||||||||||||||||||||||||||||||||||
Db 62 DSTLRLCVQSTHVDIRTLEDLLMGTLGIVGPICSQKP 98
Yan teaches an engineered HIV DNA vaccine that displays enhanced cellular immune response (Title and Abstract). Due to the high mutation rate and functional compensation of the virus, HIV vaccines are taught to have difficulty eliciting “sufficient cross-reactivity to protect against diverse circulating HIV viruses” (pg. 411, Introduction, para. 1-2). One method of improving engineered vaccines is codon optimization, RNA optimization, and “the addition of immunoglobulin (Ig) leader sequences that have weak RNA secondary structure” (pg. 411, Introduction, para. 3). Yan utilized a high-efficiency IgE leader sequence in conjunction with codon and RNA optimization to increase the immunogenicity of their vaccine construct and found that the resulting envelope DNA vaccine was up to four times more potent at eliciting cellular immune response (Abstract and pg. 411-412, Introduction, final para.). The leader sequence specifically was taught to be capable of facilitating expression of their engineered gene by being “fused in frame upstream of the start codon” (pg. 412, Construction and design of a subtype B consensus-based envelope gene).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to use the nucleic acid molecule with SEQ ID NO: 10 taught by Orlinger, modified to insert an IgE leader sequence prior to the start codon, in the invention of Daiichi because the combination of prior art elements to improve a product in a known manner yields predictable results. Daiichi teaches a lipid particle with the cationic lipid of instant claim 1, cholesterol, PEG-DMG, and DSPC in amounts that encompass or significantly overlap with the ranges recited in the instant application. Daiichi further teaches that the lipid particle can contain a nucleic acid molecule, with or without modified nucleotides/nucleosides, and can be used in a pharmaceutical composition to treat disease such as cervical cancer.
One of ordinary skill would be motivated to choose a nucleotide sequence, such as SEQ ID NO: 14, that encodes a fusion protein with SEQ ID NO: 10 from Orlinger as the nucleic acid molecule in the invention of Daiichi because Orlinger teaches that the sequence can express a protein with HPV16 E6 and E7 antigens. These antigens are taught by Orlinger to treat HPV16 infections, which are associated with cervical cancer. A person of ordinary skill would recognize that a furin cleavage site placed between the E6 and E7 coding regions in the nucleic acid sequence would enable the antigens to be separated and activated, allowing them to have their intended effect. Further, it would be obvious to the ordinary artisan that administration of a composition comprising a nucleic acid that could express HPV E6 and E7 antigens would be a viable treatment for cervical cancer, which is a goal of the invention of Daiichi.
In view of the teachings of Yan, a person of ordinary skill would be motivated to include the leader sequence based upon immunoglobulin E (IgE) in the mRNA molecule which expresses a protein containing HPV 16 E6 and E7 antigens (Orlinger, SEQ ID NO: 10) because Yan teaches the leader sequence to facilitate expression and enhance cellular immune response. The ordinary artisan would recognize this as beneficial in an engineered vaccine requiring the expression of a protein from an mRNA molecule and would therefore be motivated to include the leader sequence in their mRNA sequence. As a result, there is a reasonable expectation of success in arriving at the invention of claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 in view of the teachings of Daiichi, Orlinger, and Yan.
Response to Arguments
The Applicant’s remarks, filed on 11 December 2025, regarding the Daiichi and Orlinger references not teaching a nucleic acid molecule that contains both a coding region of a leader sequence and a 5’ untranslated region are acknowledged and the rejection above has been updated accordingly. From the penultimate para. of pg. 9 to para. 1 of pg. 10 of the remarks, Applicant details the missing leader sequence from the mRNA molecules taught by the Daiichi and Orlinger references. In view of the new grounds of rejection above, particularly the teachings of Yan that Ig leader sequences can enhance the immunogenicity of mRNA vaccines, this argument is now considered moot.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12, 14, 16, 18, 20-30, 35, 37, 53-57, 62, 64 of copending Application No. 18/561,804 in view of Orlinger (WIPO International Patent Publication No. WO 2016/198531 A2, published on 15 December 2016).
This is a provisional nonstatutory double patenting rejection.
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Copending Application No. 18/561,804 recites a lipid particle encapsulating a nucleic acid capable of expressing an E6 antigen and an E7 antigen of HPV, wherein the lipid particle contains a cationic lipid of general formula (Ia),
an amphipathic lipid, a sterol, and a PEG lipid (claims 1 and 12). The cationic lipid of general formula (Ia) may be
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(claims 2-9), the amphipathic lipid may be DSPC (claim 14), the sterol is cholesterol (claim 16), and the PEG lipid may be PEG-DMG (claim 18). Application ‘804 recites the particle to possess lipids in the amounts of 5-25% amphipathic lipid, 10-55% sterol, 40-65% cationic lipid, and 1-5% PEG lipid on a molar amount basis (claim 20). The amphipathic lipid may also be present in an amount of 10-25% (claim 21), 5-15% (claim 22), or 10-15% (claim 23), the sterol may be present in an amount of 35-50% (claim 22), 35-45% (claim 23), 10-50% (claim 25), or 10-45% (claim 26), the cationic lipid may be present in an amount of 40-55% (claim 22), 40-50% (claim 23), or 42.5-65% (claim 26), and the PEG lipid may be present in an amount of 1-3% (claim 22), 1-2.5% (claim 23), or 1-2% (claim 24 and 27). The ratio of the total weight of lipids to the weight of the nucleic acid is 15-30 (claim 28), 15-25 (claim 29), or 17.5-22.5 (claim 30). Finally, the particle is recited to have an average particle size of 30-300 nm (claim 57).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the quantities of lipids in the lipid particles recited in instant claims 20-25, the ratios of total lipid weight to total nucleic acid weight, and the diameter of the lipid particles. In each case, the copending Application ‘804 recites a range that either significantly overlaps with or encompasses the ranges recited in the instant application.
The nucleic acid sequence recited by Application ‘804 contains at least one modified nucleotide, which may be pseudouridine, optionally may be pseudouridine at the 1-position, or may be5-methyluridine (claims 53-56). The nucleic acid sequence may be an mRNA molecule that comprises E6 and E7 antigens, a cap structure, a 5’ untranslated region, a leader sequence, a protease cleavage sequence (furin cleavage site), a 3’ untranslated region, and optionally a polyA tail (claims 35 and 37). Copending Application ‘804 further recites a composition comprising the previously recited lipid nanoparticle, as well as use of the composition as a medicament, which is interpreted to be the same as a pharmaceutical composition containing the composition alongside a pharmaceutically acceptable carrier (claims 62 and 64).
Copending Application No. 18/561,804 does not recite the encapsulated nucleic acid to be an mRNA sequence capable of expressing E6 and E7 antigens for type 16 of HPV, where the E6 antigen has ≥95% identity with SEQ ID No. 8 and the E7 antigen has ≥95% identity with SEQ ID No. 9. These deficiencies are offset by the teachings of Orlinger.
Orlinger has been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to use the nucleic acid molecule with SEQ ID NO: 10 taught by Orlinger in the invention of copending Application ‘804 because the combination of prior art elements to improve a product in a known manner yields predictable results. Application 18/561,804 recites a lipid particle with the cationic lipid of instant claim 1, cholesterol, PEG-DMG, and DSPC in amounts that encompass or significantly overlap with the ranges recited in the instant application. ‘804 further recites that the lipid particle can contain a nucleic acid molecule, with or without modified nucleotides/nucleosides, that can express E6 and E7 antigens of HPV type 6 and can be used in a pharmaceutical composition.
One of ordinary skill would be motivated to choose a nucleotide sequence, such as SEQ ID NO: 14, that encodes a fusion protein with SEQ ID NO: 10 from Orlinger as the nucleic acid molecule in the invention of Application ‘804 because Orlinger teaches that HPV type 16 is correlated with cancer and that the above sequence can express a protein with HPV16 E6 and E7 antigens. A person of ordinary skill would recognize that administration of a composition comprising a nucleic acid that could express HPV E6 and E7 antigens would be a viable treatment for cervical cancer, which is known in the art to be a beneficial treatment. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 in view of claims 1-9, 12, 14, 16, 18, 20-30, 35, 37, 53-57, 62, 64 of copending Application No. 18/561,804 and the teachings of Orlinger.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are directed to an invention not patentably distinct from claims 1-9, 12, 14, 16, 18, 20-24, 28-30, 53-57, 62, 64 of commonly assigned copending Application No. 18/561,804 in view of Orlinger. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending Application No. 18/561,804, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 13-29 of U.S. Patent No. 9,803,199 B2 (priority to 7 July 2014) in view of Orlinger (WIPO International Patent Publication No. WO 2016/198531 A2, published on 15 December 2016) and Yan (Mol. Therapy 2007, 15 (1), 411.).
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U.S. Patent 9,803,199 B2 recites a lipid particle comprising the lipid having the formula:
a PEG-lipid, a sterol, and an amphipathic lipid (claims 1-4, 13, and 15). In some embodiments, the PEG-lipid is 1,2-dimyristoyl-sn-glycerol methoxypolyethylene glycol, the sterol is cholesterol, and the amphipathic lipid is DSPC (claims 5, 14, and 16-17). The total quantity of lipids contains ≤25% of the amphipathic lipid, ≥15% of the sterol, 20-70% of the cationic lipid, and 1-10% of the PEG-lipid (claim 18). The lipid particle may also comprise, with respect to the total quantity of lipids, ≤15% of the amphipathic lipid, ≥32% of the sterol, 45-65% of the cationic lipid, and 1.5-3.0% of the PEG-lipid (claim 19).
Patent ‘199 also recites the lipid particle to contain a nucleic acid, which may be a single- or double-stranded DNA, RNA, or mixed DNA/RNA molecule (claims 20-23). The ratio of the number of molecules of cationic lipid to the number of phosphorous atoms derived from the encapsulated nucleic acid is recited to be 2.0-9.0 or 3.0-9.0 (claims 24-25). Depending on the identity of the cationic lipid, total mass of the lipids in the lipid particle, and length and sequence of the encapsulated nucleic acid, the recited range may encompass the ratio of total lipid weight: weight of nucleic acid of 15-30. ‘199 further recites the average particle size of the lipid particle to be 30-300 nm, 30-200 nm, or 30-100 nm (claims 26-28). Finally, the lipid particle containing a nucleic acid is recited to be used in a pharmaceutical composition (claim 29).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the quantities of lipids in the lipid particles recited in instant claims 20-25, the ratios of total lipid weight to total nucleic acid weight, and the diameter of the lipid particles. In each case, patent ‘199 recites a range that either significantly overlaps with or encompasses the ranges recited in the instant application.
Commonly assigned U.S. Patent No. 9,803,199 B2 does not recite the encapsulated nucleic acid to be an mRNA sequence capable of expressing E6 and E7 antigens for type 16 of HPV, where the E6 antigen has ≥95% identity with SEQ ID No. 8 and the E7 antigen has ≥95% identity with SEQ ID No. 9. These deficiencies are offset by the teachings of Orlinger and Yan.
Orlinger and Yan have been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to use the nucleic acid molecule with SEQ ID NO: 10 taught by Orlinger in the invention of patent ‘199 because the combination of prior art elements to improve a product in a known manner yields predictable results. U.S. Patent 9,803,199 B2 recites a lipid particle with the cationic lipid of instant claim 1, cholesterol, PEG-DMG, and DSPC in amounts that encompass or significantly overlap with the ranges recited in the instant application. ‘199 further recites that the lipid particle can contain a nucleic acid molecule and can be used in a pharmaceutical composition.
One of ordinary skill would be motivated to choose a nucleotide sequence, such as SEQ ID NO: 14, that encodes a fusion protein with SEQ ID NO: 10 from Orlinger as the nucleic acid molecule in the invention of patent ‘199 because Orlinger teaches that HPV type 16 is correlated with cancer and that the above sequence can express a protein with HPV16 E6 and E7 antigens. A person of ordinary skill would recognize that administration of a composition comprising a nucleic acid that could express HPV E6 and E7 antigens would be a viable treatment for cervical cancer, which is known in the art to be a beneficial treatment.
In view of the teachings of Yan, a person of ordinary skill would be motivated to include the leader sequence based upon immunoglobulin E (IgE) in the mRNA molecule which expresses a protein containing HPV 16 E6 and E7 antigens (Orlinger, SEQ ID NO: 10) because Yan teaches the leader sequence to facilitate expression and enhance cellular immune response. The ordinary artisan would recognize this as beneficial in an engineered vaccine requiring the expression of a protein from an mRNA molecule and would therefore be motivated to include the leader sequence in their mRNA sequence. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 in view of claims 1-5 and 13-29 of commonly assigned U.S. Patent 9,803,199 B2 and the teachings of Orlinger and Yan.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are directed to an invention not patentably distinct from claims 1-5 and 13-29 of commonly assigned U.S. Patent No. 9,803,199 B2 in view of Orlinger and Yan. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 9,803,199 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 14-17, and 25-45 of U.S. Patent No. 10,533,176 B2 (priority to 30 October 2017) in view of Orlinger (WIPO International Patent Publication No. WO 2016/198531 A2, published on 15 December 2016) and Yan (Mol. Therapy 2007, 15 (1), 411.).
U.S. Patent No. 10,533,176 B2 recites a lipid of formula (Ia):
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wherein R1=R2=methyl; R8=H; L1=C17-19 alkenyl group, optionally substituted with a C2-4 alkanoyloxy group; L2=C10-12 alkyl group or alkenyl group; m=0; p=0, 1, or 2; r=0, 1, 2, or 3; and p+r=2 or 3 (claim 1). In one embodiment, the lipid of formula (Ia) is:
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which is identical to the lipid in instant claim 1 (claims 2-8). Patent ‘176 further recites a lipid particle comprising the lipid of formula (Ia), a PEG-lipid, a sterol, and an amphipathic lipid (claims 14-16, 25, and 27). In some embodiments, the PEG-lipid is 1,2-dimyristoyl-sn-glycerol methoxypolyethylene glycol (PEG-DMG), the sterol is cholesterol, and the amphipathic lipid is DSPC (claims 17, 26, and 28-29). The total quantity of lipids contains ≤25% of the amphipathic lipid, ≥15% of the sterol, 20-70% of the cationic lipid, and 1-10% of the PEG-lipid (claim 30). The lipid particle may also comprise, with respect to the total quantity of lipids, ≤15% of the amphipathic lipid, ≥32% of the sterol, 45-65% of the cationic lipid, and 1.5-3.0% of the PEG-lipid (claim 19).
Patent ‘176 also recites the lipid particle to contain a nucleic acid, which may be a single- or double-stranded DNA, RNA, or mixed DNA/RNA molecule (claims 32-35). The ratio of the number of molecules of cationic lipid to the number of phosphorous atoms derived from the encapsulated nucleic acid is recited to be 2.0-9.0 or 3.0-9.0 (claims 24-25). Depending on the identity of the cationic lipid, total mass of the lipids in the lipid particle, and length and sequence of the encapsulated nucleic acid, the recited range may encompass the ratio of total lipid weight: weight of nucleic acid of 15-30. ‘176 further recites the average particle size of the lipid particle to be 30-300 nm, 30-200 nm, or 30-100 nm (claims 38-40). Finally, the lipid particle containing a nucleic acid is recited to be used in a pharmaceutical composition, alongside a pharmaceutically acceptable carrier, and may be used to treat a disease such as cancer by enacting a “gene expression effect on [a] target gene” (claim 41-45).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the quantities of lipids in the lipid particles recited in instant claims 20-25, the ratios of total lipid weight to total nucleic acid weight, and the diameter of the lipid particles. In each case, patent ‘176 recites a range that either significantly overlaps with or encompasses the ranges recited in the instant application.
Commonly assigned U.S. Patent No. 10,533,176 B2 does not recite the encapsulated nucleic acid to be an mRNA sequence capable of expressing E6 and E7 antigens for type 16 of HPV, where the E6 antigen has ≥95% identity with SEQ ID No. 8 and the E7 antigen has ≥95% identity with SEQ ID No. 9. These deficiencies are offset by the teachings of Orlinger and Yan.
Orlinger and Yan have been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to use the nucleic acid molecule with SEQ ID NO: 10 taught by Orlinger in the invention of patent ‘176 because the combination of prior art elements to improve a product in a known manner yields predictable results. U.S. Patent 10,533,176 B2 recites a lipid particle with the cationic lipid of instant claim 1, cholesterol, PEG-DMG, and DSPC in amounts that encompass or significantly overlap with the ranges recited in the instant application. ‘176 further recites that the lipid particle can contain a nucleic acid molecule, with or without modified nucleotides/nucleosides, that can express E6 and E7 antigens of HPV type 6 and can be used in a pharmaceutical composition.
One of ordinary skill would be motivated to choose a nucleotide sequence, such as SEQ ID NO: 14, that encodes a fusion protein with SEQ ID NO: 10 from Orlinger as the nucleic acid molecule in the invention of patent ‘176 because Orlinger teaches that HPV type 16 is correlated with cancer and that the above sequence can express a protein with HPV16 E6 and E7 antigens. A person of ordinary skill would recognize that administration of a composition comprising a nucleic acid that could express HPV E6 and E7 antigens would be a viable treatment for cervical cancer, which is known in the art to be a beneficial treatment.
In view of the teachings of Yan, a person of ordinary skill would be motivated to include the leader sequence based upon immunoglobulin E (IgE) in the mRNA molecule which expresses a protein containing HPV 16 E6 and E7 antigens (Orlinger, SEQ ID NO: 10) because Yan teaches the leader sequence to facilitate expression and enhance cellular immune response. The ordinary artisan would recognize this as beneficial in an engineered vaccine requiring the expression of a protein from an mRNA molecule and would therefore be motivated to include the leader sequence in their mRNA sequence. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 in view of claims 1-8, 14-17, and 25-45 of commonly assigned U.S. Patent 10,533,176 B2 and the teachings of Orlinger and Yan.
Claims 1, 12, 14, 16, 18, 20-24, 27-31, 33, 41-45, 48, and 50 are directed to an invention not patentably distinct from claims 1-8, 14-17, and 25-45 of commonly assigned U.S. Patent No. 10,533,176 B2 in view of Orlinger and Yan. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 10,533,176 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Response to Arguments
In para. 2, 4, and 6 of the section titled “Double Patenting Rejections” on pg. 10 of the remarks filed on 11 December 2025, Applicant “respectfully rested the double patenting rejection[s] be held in abeyance until the patentability of all claims is indicated”. A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by the Applicant showing that the claims subject to the restriction are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.
Allowable Subject Matter
Claims 32, 34, and 70 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. In particular, the prior art is free of nucleic acids capable of expressing a protein with an amino acid sequence with ≥95% identity with SEQ ID NO: 17 and nucleic acids with sequences that have ≥90% identity with SEQ ID NO: 2, 4, or 6
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Yijayachari et al. (Human Vacc. Imuunother. 2015, 11 (8), 1945.) teach the immunogenicity of a novel, enhanced DNA vaccine which a membrane lipoprotein of Leptospria bacteria (Abstract). An IgE leader sequence was used by Yijayachari et al. to “enhance translation of the [vaccine] construct in addition to increasing the immunogenicity of the translated product” (pg. 1950, right col., para. 1).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sean J. Steinke, Ph.D., whose telephone number is (571) 272-3396. The examiner can normally be reached Mon. - Fri., 09:00 - 17:00 ET.
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/S.J.S./
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619