DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of invention I and the required species in the replies filed on 11/13/25 and 7/1/26 are acknowledged.
Applicants have elected the species of SEQ ID NO:s 11 and 18 and the PEGylated lipid of DMG-PEG2000.
SEQ ID NO: 11 is identified as A2-T160F_N46V and as the following amino acid sequence: MSWKVVIIFSLLITPQHGLKESYLEESCSTITEGYLSVLRTGWYTVVFTLEVGDVENLTC
SDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIA LGVATAAAVTA
GVAIA KTIRLESEVTAIKNALKTTNEAVSTLGNGVRVLAFAVRELKDFVSKNLTRAINKN
KCDIDDLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSNMPTSAGQIKLMLENRAMVRRKGFGILIGVYGSSVIYMVQLPIFGVIDTPCWIVKAAPSCSEKKGNYACLLREDQGWYCQNAGSTVYYPNEKDCETRGDHVFCDTAAGINVAEQSKECNINISTTNYPCKVSTGRHPISMVALSPLGALVACYKGVSCSIGSNRVGIIKQLNKGCSYITNQDADTVTIDNTVYQLSKVEGEQHVIKGRPVSSSFDPIKFPEDQFNVALDQVFENIENSQALVDQSNRILSSAEKGNTGFIIVIILIAVLGSSMILVSIFIIIKKTKKPTGAPPELSGVTNNGFIPHN
The underline and italicized portion is the transmembrane domain and the bolded text is the cytoplasmic tail.
SEQ ID NO: 18 encodes SEQ ID NO: 11. In view of applicants electing SEQ ID NO: 11 and 18, the following claims require these sequences and will be examined, claims 34, 100 and 101. As a result, the elected species of DMG-PEG2000 is withdrawn at this time.
Claims 65, 66, 71 and 78 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/23/25. These claims have been cancelled by applicant.
Claims 1, 2, 7, 10, 19, 20, 23, 28, 29, 31-33, 35, 38, 41, 44, 45, 53, 54, 59, 61, 63, 64, 75, 76, 92-99 and 102-104 are withdrawn as drawn to non-elected species.
Claims 34, 100 and 101 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/20/22, 4/21/23, 7/25/23, 11/13/25 and 7/1/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 34 and 100 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally-occurring element of nature that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology V. Myriad Genetics, Inc., -- U.S. -- (June 13, 2013) (hereafter "Myriad").
Based upon an analysis with respect to the claims as a whole, claim(s) 34 and 100 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The claims do not fall within at least one of the four categories of patent eligible subject
matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more (these claims are interpreted in light of the most recent Guidelines (See 'https://www.uspto.gov/patent/laws-and-
regulations/examination-policy/subject-matter-eligibility).
These claims are analyzed for eligibility in accordance with their broadest reasonable
interpretation. In view of the Subject Matter Eligibility Test for Products and Processes the claims are directed to an ineligible product/process as further detailed below.
In this case, claim(s) 34 and 100 recite an mRNA comprising an open reading frame encoding a human metapneumovirus (hMPV) F polypeptide antigen comprising an amino acid sequence with at least 95% identity to SEQ ID NO: 11 and a nucleic acid sequence encoding the polypeptide that is at least 95% identity to SEQ ID NO: 11. Therefore, these claims are drawn to a composition of matter (Step 1) and recite natural phenomenon(s) (in this case, a naturally occurring polypeptide and nanoparticle comprising it) that are directed to a judicial exception (in this case, a natural phenomenon)(Step 2A).
GenBank Accession QDA18383 presents the amino acid sequence of a F protein of a hMPV strain 4854-A2 that was isolated from an infant in Napal, which establishes that the F protein is a naturally occurring product of nature. QDA18383 is 98% identical to SEQ ID NO: 11 of the instant invention and it is encoded by GenBank Accession MK177113, which represents genomic RNA of the 4854-A2 strain. Therefore, MK177113 is also a naturally occurring nucleic acid sequence that encodes a hMPV F protein with at least 95% identity to SEQ ID NO: 11. Kruger et al. (Drug Discovery Today, 2025, Vol. 30, No. 5) also teach that during the replication of the hMPV genome, the mRNA intermediate sequences that are translated into hMPV proteins are naturally occurring. [see page 3, section “Viral Structure and replication of hMPV”] Therefore, the mRNA of strain 4854-A2 for the Fusion protein is also naturally occurring.
Therefore, the claimed mRNA and nucleic acid are interpreted as naturally occurring.
Thus the claimed product is not markedly different from its naturally occurring counterpart. To summarize, the claims read upon a composition of matter as recited in Step 1 and a natural phenomenon as recited in Step 2A and the claims do not recite the integration of the judicial exception into a practical application.
Further, in view of Step 2B and the "No" pathway, the claims do not recite additional
elements that amount to significantly more than the judicial exception. The claimed invention does not require a limitation that does not amount to significantly more than the judicial exception.
As pursuant to the Office's interpretation of the Myriad decision, a recitation of a naturally-occurring nucleic acid, or any natural product of nature that does not have a substantial or marked difference from the natural product is not patent eligible subject matter.
Therefore, claims 34 and 100 as written, read upon a naturally occurring mRNA and nucleic acid sequences that were found to have occurred naturally in nature without being subject to the "hand-of-person" and resulting in a substantial or markedly different product from that found in nature.
Therefore, claim(s) 34 and 100 do not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes, and the claimed invention is directed to non-statutory subject matter.
This rejection is necessitated by expanded 35 USC § 101 USPTO training in view of the
USPTO's interpretation of Myriad. Applicant is directed towards the USPTO memos, which support the analysis of the claims; please review the latest materials regarding 35 USC § 101 rejections. Applicant is cautioned to amend the claims according to these suggestions utilizing limitations for which the application would have support.
Claim Rejections - 35 USC § 112
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 34, 100 and 101 are rejected under 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant broadly claims a mRNA sequence or a nucleic acid containing the nucleic acids of claims 34, 100 and 101. The claims read on a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the nucleic acid.
With respect to the unisolated transgenes as “nucleic acids” of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, Vol. 45, Pg. 57-68, 1996).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the antibody and antibody fragments of the instant claims.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) states that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099- 1112) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins, 1989, EMBO J., Vol. 8, pages 183-191). Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another.
The examiner notes here, in addition to these issues, even assuming arguendo a person having ordinary skill in the art could make a host organism with functional transgene that encodes the instantly recited SEQ ID NO: 11, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
The art is well-aware of side effects caused by expressing proteins, such as therapeutic antibodies. In a transgenic cell or animal that expresses the same, the antibody will exert any possible side effect it can. It is not administered but chronically present and so such side effects are chronic and potentially more serious than any from an administered antibody. Hansel (Nature Reviews Drug Discovery, Vol. 9, Pg. 325-337, 2010) teaches in their table 1 on page 328 numerous exemplary side effects from licensed monoclonal antibodies to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS) to name only a few. One or more such effects, or similar, may occur with the therapeutic antibody instantly recited when administered and indeed be exacerbated by chronic exposure due to internal expression. For all these reasons, previously raised and new, transgenes are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "host cell" and by amending the vector and polynucleotide claims to specify they are not in a transgenic animal. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use transgenic animals possessing the claimed host cells, nucleic acid, or expression vector, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed host cell, nucleic acid, or expression vector, commensurate in scope with the claimed invention. The same can be said for the transgenes and transgenic animals encompassed by the instant claims. Thus, the claims are rejected here.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 100 is rejected under 35 U.S.C. 102a1 as being anticipated by GenBank Accession MK177113 (6/17/2019) as evidenced by GenBank Accession QDA18383 (6/17/2019).
A nucleic acid molecule encoding the hMPV F polypeptide antigen comprises an amino acid sequence with at least 95% identity to SEQ ID NO: 11.
QDA18383 is 98% identical to SEQ ID NO: 11 of the instant invention and it is encoded by GenBank Accession MK177113, which represents a genomic RNA sequence of the 4854-A2 strain. Therefore, MK177113 anticipates the claimed invention.
Claims 34 and 100 are rejected under 35 U.S.C. 102a1 as being anticipated by Ciaramella et al. (US PGPub 20170340725).
The claimed invention is drawn to a messenger RNA (mRNA) comprising an open reading frame (ORF) encoding a human metapneumovirus (hMPV) F polypeptide antigen, wherein the hMPV F polypeptide antigen comprises an amino acid sequence with at least 95% identity to SEQ ID NO: 11.
The claimed invention also requires a nucleic acid molecule encoding the hMPV F polypeptide antigen comprises an amino acid sequence with at least 95% identity to SEQ ID NO: 11.
Ciaramella et al. teach at paragraph [0026] “In some embodiments, a RNA (e.g., mRNA) vaccine comprises at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one hMPV, PIV3 or RSV antigenic polypeptide. In some embodiments, at least one antigenic polypeptide is a hMPV, PIV3 or RSV polyprotein. In some embodiments, at least one antigenic polypeptide is major surface glycoprotein G or an immunogenic fragment thereof. In some embodiments, at least one antigenic polypeptide is Fusion (F) glycoprotein (e.g., Fusion glycoprotein F0, F1 or F2) or an immunogenic fragment thereof. In some embodiments, at least one antigenic polypeptide is major surface glycoprotein G or an immunogenic fragment thereof and F glycoprotein or an immunogenic fragment thereof. In some embodiments, the antigenic polypeptide is nucleoprotein (N) or an immunogenic fragment thereof, phosphoprotein (P) or an immunogenic fragment thereof, large polymerase protein (L) or an immunogenic fragment thereof, matrix protein (M) or an immunogenic fragment thereof, small hydrophobic protein (SH) or an immunogenic fragment thereof nonstructural protein1(NS1) or an immunogenic fragment thereof, or nonstructural protein 2 (NS2) and an immunogenic fragment thereof.
[0027] In some embodiments, at least one hMPV antigenic polypeptide comprises an amino acid sequence identified by any one of SEQ ID NO: 5-8 (Table 3; see also amino acid sequences of Table 4). In some embodiments, the amino acid sequence of the hMPV antigenic polypeptide is, or is a fragment of, or is a homolog or variant having at least 80% (e.g., 85%, 90%, 95%, 98%, 99%) identity to, the amino acid sequence identified by any one of SEQ ID NO: 5-8 (Table 3; see also amino acid sequences of Table 4).”
SEQ ID NO: 5 is Ciaramella et al. is 98.7% identical to SEQ ID NO: 11.
Therefore, Ciaramella et al. anticipates the instant invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 34, 100 and 101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of copending Application No. 18660489 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of claim 1 from ‘489 is drawn to a composition comprising a mRNA encoding the F protein of hMPV comprising the amino acid sequence of SEQ ID NO: 2, which is identical to SEQ ID NO: 11 of the instant invention. A specific example of an mRNA from ‘489 is SEQ ID NO: 5, which is 99.9% identical to SEQ ID NO; 18 of the instant invention. Therefore, the composition of ‘489 teaches the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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