DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. This Office Action is in response to the amendment filed 17 March 2026, wherein claims 1, 3, 5, 7-12, and 15-17 were amended; claims 2, 4, and 6 were canceled, and claim 18 was added.
Claims 1, 3, 5, and 7-18 are under consideration.
Objections Withdrawn
Specification
3. The objection to the specification for use of trade names or trademarks without proper identifier is withdrawn in view of Applicant’s amendments.
4. The objection to the specification for disclosed sequences missing SEQ ID NOs is withdrawn in view of Applicant’s amendments.
Claim Objections
5. The objections to claims 2, 6, 11, and 16 are withdrawn in view of Applicant’s amendments.
Claim Rejections - 35 USC § 112
6. The rejections of claims 3, 4, and 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite are withdrawn in view of Applicant’s amendments.
Claim Rejections - 35 USC § 102
7. The rejection of claims 1-3 and 5-17 under 35 U.S.C. 102(a)(2) as being anticipated by Grobe (US 20240181037 A1; provisional filed 26 March 2021) is withdrawn in view of Applicant’s amendments.
8. The rejection of claims 1-4, 7-10, and 12-17 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Ciaramella (US 20210187097 A1; provisional filed 15 March 2017) is withdrawn in view of Applicant’s amendments.
Double Patenting
9. The rejection of claims 1, 7-8, 10-14, and 16 on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 11, and 14-19 of copending Application No. 19/098,884 is withdrawn in view of Applicant’s amendments.
10. The rejection of claims 1, 6-8, and 10-14 on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 11, and 15-19 of U.S. Patent No. 12,280,102 is withdrawn in view of Applicant’s amendments.
Objections Maintained
Specification
11. The objection to the specification for having embedded hyperlinks or browser-executable code is maintained. Applicant should remove “www.” before recitation of links. See ¶ [0005] and [0089].
Claim Interpretation
12. The specification teaches “sub-genomic promoters” (¶ [0044]) and “SG promoter” (¶ [0100]), but does not teach that “SG” is an abbreviation for “sub-genomic”. However, since there are no other promoters contemplated that could be reasonably interpreted as an “SG” promoter (¶ [0066]), Examiner is interpreting “SG promoter” to only read on subgenomic promoters.
13. Claim 1 is being interpreted as reading on one polynucleotide which encodes two separate polypeptides, one with alphavirus nsp1, nsp2, nsp3, and nsp4; and the other with an antigen protein fused to a signal sequence and transmembrane domain. Similarly, claim 17 is being interpreted as two separate proteins expressed in the target cell. This is consistent with what is taught in the Instant Specification. See ¶ [0009]-[0010] and [0012] and the new matter rejection infra.
New Objections
Claim Objections
14. Claims 10-11 are objected to because of the following informalities:
Regarding claim 10, “A vector” should read “An isolated vector”.
Similarly, claim 11 should read “The isolated vector”.
Both these objections are made to improve clarity and consistency with the specification.
Regarding claim 11, each main item in the list should be separated with semicolons to improve readability.
Appropriate correction is required.
New Rejections
Claim Rejections - 35 USC § 112(a) – Written Description
15. 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.
16. Claims 12-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims above are drawn to a vaccine composition comprising the isolated polynucleotide of claim 1, which recites encoding a polypeptide comprising a head region of HA1. This reads on partial sequences of HA1 head. However, the specification does not provide working examples of a vaccine and thus no evidence that just any subsequence of HA1 head domain functions as a preventative. Vaccination implies that the encoded polypeptide is able to produce neutralizing antibodies. Thus, it is clear that the breadth of the recited peptides in the claims far overreaches Applicant’s contribution as disclosed in the specification and so this rejection is made. One of ordinary skill in this art cannot conclude that Applicant was in possession of a vaccine with just any peptide encoded by the isolated polynucleotide of claim 1. An enormous breadth of vaccines is thus not represented by Applicant at all. Even if the prior art is aware of vaccines with these isolated polynucleotides, the totality of known vaccines would not be representative of the entire genus for the reasons discussed below.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the HA1 head region can be a fragment thereof, one must describe a sufficient variety of species to reflect the variation within the genus. However, one of skill in this art cannot envision the structure of any other peptides with the required function other than the few species provided by Applicant and the prior art. Therefore, since only a few species are provided to represent the genus, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010). Since there are only a few presented constructs taught by Applicant, and mutated polypeptides would vary in structure, there is no correlation between structure and function between the members of the recited genus. Additional mutated polypeptides could read on any and all combinations of amino acids. Thus, since there is no correlation between structure and peptide function across the entire genus, functional language should not be used to define a peptide genus. Rather, structure should be used, including the core peptide sequence required for said function. There is no indication that every single possible isolated polypeptide will be able to incur neutralizing antibodies.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since the genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
Overall, at the time the invention was made, the level of skill for preparing peptides and then selecting those peptides with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify peptides with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010). Absent the conserved structure provided by a core inhibitory peptide sequence, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what any peptide with a particular set of functional properties would look like structurally.
Since no HA1 head fragments are taught in the specification of the recited genus above, the instant claims above clearly fail the written description requirement. A representative number of species has not been taught to describe such a massive genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe said genus.
Owed to the variation among the peptides of the genus as broadly as currently claimed, it is very difficult to provide adequate representation of the functionally defined peptide genus. There is unlikely to be any structure (subsequence) shared by the entire genus. If there is a subsequence common to all or some of Applicant’s species, then the claims should recite that as part of the peptide genus to provide adequate representation of the actual disclosed/possessed group. Also, the disclosure of one group of highly related peptides does not guide one of skill to the next peptide of the genus with said function. Finding another said peptide would require mutation and it is well-known in this art that mutation of peptides leads to specific function loss.
In addition, changing the immunogen might eliminate vaccine function. For example, Kodihalli (August 1995, J. Virol., 69(8): 4888-4897) teaches that a single amino acid substitution in the hemagglutinin molecule of influenza A can influence the effectiveness of the subsequent vaccine candidate (Abstract). A substitution of lysine instead of glutamic acid at position 156 caused the vaccine to be poorly immunogenic, while the substitution of isoleucine instead of serine at position 186 didn’t have a significant effect on the vaccine’s immunogenicity (Abstract). Therefore, even changing the immunogen by one amino acid may render the vaccine ineffective and even bigger mutations, such as truncation, could also eliminate vaccine function.
Thus, while applicant has described a few species within the genus recited, and the art may provide more, each genus is very large and would encompass peptide structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the peptide structures encompassed by the claimed/recited genus only defined by function. Any future peptide may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. In addition, there is no guarantee that every variation of the immunogen will produce neutralizing antibodies and be effective in a vaccine. Thus, the described species cannot be considered representative of the entire recited genus of peptides. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) and the claims are rejected here.
17. Claims 1, 3, 5, 7-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
All claims rejected above read on a polypeptide comprising all of: nsp1-4, an antigen fused to a signal sequence, and a transmembrane domain; nucleic acids encoding the same; or methods using these products. However, the construct design of such a large single fusion protein with all domains recited above is new matter. A fusion of nsp1-4 is not recited in the original claims or specification. The closest teaching is in the specification at ¶ [0009]-[0010] and [0012] where it teaches nsp1-4 as separate proteins and so not fused together. Original Figure 2 does appear to show nsp1-4 fused to one another as one encoded protein. However, Figure 2 clearly shows a separate promoter for the HA fusion proteins. Therefore, the original disclosure does not support the full breadth of the claims and they are rejected here.
Claim Rejections - 35 USC § 112(a) – Enablement
18. Claims 12-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for any epitopes of the head region that are shown to give neutralizing antibodies, does not reasonably provide enablement for any and all possible head region epitopes. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
The claims are drawn to a vaccine composition comprising the isolated polynucleotide of claim 1 and methods thereof.
The nature of the invention is a vaccine composition.
The level of skill of one of ordinary skill in this art is high.
The specification provides examples of constructs, but does not provide any working examples for the vaccine composition or demonstrates that the epitopes produce neutralizing antibodies.
Reasonable guidance with respect to preventing any viral infection relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of viruses. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical infection and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Further, a preventive administration also must assume that the therapeutic will be safe and tolerable for anyone susceptible to the disease. Therefore, Applicant may provide data showing prevention in vivo.
As stated in Cross v. Iizuka, 753 F.2d 1040, 1050, 224 USPQ 739, 747 (Fed. Cir. 1985): [B]ased upon the relevant evidence as a whole, there is a reasonable correlation between the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is not necessary where the disclosure of pharmacological activity is reasonable based upon the probative evidence. (Citations omitted.) Therefore, in the absence of the in vivo data above, Applicant may also provide evidence of pharmacological activity that would reasonably correlate with prevention of infection.
In the case of virus vaccines, a reasonable nexus exists between neutralizing antibody generation and prevention of infection. Thus, a showing that an antigen within the recited immunogen scope can produce such antibodies would support enablement for use of said antigen in a vaccine and/or methods of preventing infection therewith of the virus comprising said antigen.
Burton (2002, Nat. Rev. Immunol., 2: 706-713) teaches neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases (Abstract). Figure 1 divides antiviral activities of antibodies into two groups: activities against free virus and activities against infected cells. Actual block of infection (prevention of infection) is taught to be the role of neutralizing antibodies (Figure 1). Nonneutralizing antibodies thus cannot prevent infection, only treat an infection.
Adding to the unpredictability is the fact that not just any epitope of a target antigen/virus will lead to antibody generation, let alone that of neutralizing antibodies. Riddell (2000, J. Virol., 74(17): 8011-8017) at the abstract teaches patient sera reacts with some but not all B-cell epitopes on ORF7.1 protein. Thus, not just any epitope/antigen/immunogen will contribute to patient immunity against a virus. Sugiyama (2002, J. Virol., 76(4): 1691-1696) supports this by teaching in their abstract that even amongst known epitopes that lead to neutralizing antibodies in some species, another subject’s immune reaction will not necessarily generate antibodies against all said epitopes.
Burton (2011, PNAS, 108(27): 11181-11186) teaches three anti-HIV antibodies. Antibodies b12 and b6 bind CD4 binding sites while F240 binds gp41 (Abstract). All were tested for prevention of SHIV transmission to macaques (Abstract). While the two anti-gp120 antibodies have similar binding properties, b12 is strongly neutralizing and b6 is not (Abstract). F240 is nonneutralizing (Abstract). Compared to controls, the protection by b12 achieved statistical significance while no such protection was seen for either b6 or F240 (Abstract). Thus, the work of Burton supports the conclusion that neutralizing antibodies are required for prevention and so a functional vaccine should produce such. It also supports the idea that not just any peptide on protein may generate neutralizing antibodies that protect as evidenced by b12 and b6 performance above. Data are clearly required to calm the concerns of the prior art and make methods of viral infection prevention and vaccine products predictable.
Taken together, it is clear from the prior art that a person of ordinary skill in the art cannot predict the preventative power of any immunogen. They must be shown data that supports such a conclusion. Without demonstration of neutralizing antibody production, for example, in the target population with the specific immunogen, no practitioner in this art would see any given immunogen as a functional, predictable prophylactic agent.
Claim Rejections - 35 USC § 103
19. 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.
20. 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.
21. Claims 1, 3, 5, and 7-18 are rejected under 35 U.S.C. 103 as being unpatentable over Grobe (US 20240181037 A1; provisional filed 26 March 2021) (See PTO-892 filed 17 November 2025) in view of Farsad (2016, Iran. J. Vet. Res., 17(4): 237-242) and Shirvani (04 June 2020, Front. Microbiol., 11: 1085).
Regarding claims 1, 3, 5, 7-8, and 17-18, Grobe teaches a carrier-formulated mRNA for influenza immunization (Abstract and ¶ [0003]), with “mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide.” (¶ [0014]), which comprises HA2 and part of HA1 (¶ [0005]). The reference also teaches that the mRNA can be an alphavirus-derived mRNA replicon (¶ [0523]), which encodes an RNA polymerase (with nsp1-4) and antigen, such as the HA stem polypeptide (¶ [0526]). The polymerase can comprise one or more alphavirus proteins nsp1, nsp2, nsp3, and nsp4 (¶ [0526]). Therefore, it would be obvious to have nsp1, nsp2, nsp3, and nsp4 all on the same polypeptide. Figure 69 shows a polynucleotide encoding two polypeptides: one with nsp1-4 and the other with a signal peptide, the HA stem, and ferritin derived from H. pylori:
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In addition, Grobe teaches “the mRNA comprises at least one additional coding sequence which encodes one or more heterologous peptide or protein elements selected from a signal peptide, a linker, […], a transmembrane element, a protein nanoparticle…” (¶ [0046]). In summary, Grobe teaches a polynucleotide with alphavirus nsp1-4 and an HA stem antigen protein fused to a signal sequence, and makes it obvious to add a transmembrane domain as well as a linker to fuse the transmembrane domain to the HA stem. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
For the HA stem antigen protein, Grobe specifically teaches enabled sequences (¶ [0063]-[0075]). Grobe further teaches “antibodies against influenza often target variable antigenic sites in the globular head of HA and thus, neutralize only antigenically closely related viruses.” (¶ [0006]) and “However, robustly eliciting these antibodies in subjects by vaccination with the HA stem, lacking the head domain, has been difficult” (¶ [0008]). Grobe does not teach a specific HA1 head sequence.
However, Farsad teaches using the HA1 head as an antigen for an influenza vaccine (Abstract), wherein “The HA1 sequence, encompassing amino acids 1-320 of the A/Indonesia/05/05 strain of H5N1 influenza virus (AFM78567.1)” (Cloning of the recombinant HA1 protein, ¶ 1). Therefore, using the head region of the HA protein as influenza immunogens is known and routinely used in the art and it would have been obvious to one of ordinary skill before the time of filing to take the polynucleotide of Grobe and replace the HA stem with the HA1 head region of Farsad. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.). The substitution above is merely substitution of one known influenza immunogen for another. Alternatively, one could use the head region fused to the stem since both are part of the same protein and both taught in the art for the same purpose, immunogens in vaccines against influenza. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
It would be further obvious to use the full-length HA protein instead of a fragment. Shirvani teaches “Immunization with HA1 or HA2 alone neither induced serum neutralizing antibodies nor prevented death following challenge. Our results suggest that interaction of HA1 and HA2 subunits is necessary for the display of epitopes on HA protein involved in the induction of neutralizing antibodies and protection. These epitopes are lost when the two subunits are separated.” (Abstract). Therefore, it would have been obvious to one of ordinary skill before the filing date to take the methods and products of Grobe and further substitute the antigen for the full-length HA protein of Farsad in order to elicit a better immune response, as discussed by Shirvani. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
Regarding claim 9, Grobe teaches that the mRNA is an in vitro transcribed RNA in which “RNA may be obtained by DNA-dependent in vitro transcription of an appropriate DNA template…” (¶ [0470] and [0471]), which indicates the usage of an isolated DNA polynucleotide.
Regarding claim 10, Grobe teaches a vector comprising the polynucleotide: “The self-replicating RNA can conveniently be prepared by in vitro transcription (IVT). IVT can use a (cDNA) template created and propagated in plasmid form in bacteria…” (¶ [0533]). Therefore, it would have been obvious before the time of filing to take the polynucleotide and put it in a vector. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Regarding claim 11, Grobe teaches the signal peptide and transmembrane element and the alphavirus nsps (supra), as well as “In some embodiments, the mRNA has the configuration 5’cap-5’UTR-nonstructural proteins (NSP) 1-4-subgenomic promoter-influenza HA stem polypeptide-linker-protein nanoparticle-3’UTR-polyA.” (¶ [0129]) and “For example, the mRNA may comprise […] a control sequence such as a promoter…” (¶ [0353]). For the reasons discussed supra, it would have been obvious to substitute the HA stem polypeptide with a HA head polypeptide. It would have also been obvious before the time of filing to add the signal peptide and transmembrane element to the mRNA construct, fused by a linker to the antigen. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02). Use of both a promoter and subgenomic promoter are obvious since the nsp1-4 discussed above require transcription and thus a promoter to initiate that for them as is well-known in this art.
Regarding claim 12, Grobe teaches “Also provided is an immunogenic composition comprising the carrier-formulated mRNA as defined herein, wherein the composition optionally comprises at least one pharmaceutically acceptable carrier.” (¶ [0130]). Therefore, it would have been obvious before the time of filing to make a vaccine composition with the obvious polynucleotide above. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Regarding claims 13 and 14, Grobe teaches “In embodiments, the mRNA of the invention is complexed, encapsulated, partially encapsulated, or associated with one or more lipids (e.g. cationic lipids and/or neutral lipids), thereby forming lipid-based carriers such as liposomes, lipid nanoparticles (LNPs), lipoplexes, and/or nanoliposomes, suitably lipid nanoparticles.” (¶ [0545]).
Regarding claims 15 and 16, Grobe teaches “Also provided is a method of eliciting an immune response, wherein the method comprises applying or administering to a subject in need thereof the carrier-formulated mRNA as defined herein, the composition as defined herein, the vaccine as defined herein or the kit or kit of parts as defined herein.” (¶ [0151]) and “Also provided is a method of treating or preventing a disorder, wherein the method comprises applying or administering to a subject in need thereof the carrier-formulated mRNA as defined herein, the composition as defined herein, the vaccine as defined herein or the kit or kit of parts as defined herein.” (¶ [0148]).
Response to Traversal
22. Applicant argues that Grobe teaches away from using the head portion of the influenza HA. However, Grobe teaches “antibodies against influenza often target variable antigenic sites in the globular head of HA and thus, neutralize only antigenically closely related viruses.” (¶ [0006]) and “However, robustly eliciting these antibodies in subjects by vaccination with the HA stem, lacking the head domain, has been difficult” (¶ [0008]). Therefore, using the head region of the HA protein as influenza immunogens is known and routinely used in the art. Grobe is simply teaching a new method of preparing influenza immunogens using solely the stem region of the HA protein. There is no indication that including the head region would not work.
23. Applicant argues that Ciaramella teaches away from self-replicating or self-amplifying RNA. Ciaramella does not teach that use of self-replicating RNA would render the obvious invention above or any mRNA nonfunctional and so is not a true teaching away. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Thus, the mere teaching of use of one type of RNA does not logically teach away from a second functional embodiment.
Since the teaching away arguments are addressed, the 103 above can and should be presented on record.
Conclusion
24. No claim is allowed. 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.
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/KRISTINA E. LY/Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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