DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 10/13/2025.
Claims 13, 15, 16 and 21-37 are pending.
The instant application claims priority as a divisional application of 15/723,658 filed 10/3/2017 now U.S. Patent 11,364,310 which claims priority to US provisional 62/409,228 filed 10/17/2016.
Response to Amendments
The previous objections and rejections have been overcome by amendment.
Claim Objections
These objections are necessitated by applicants amendments.
Claims 22, 23, 30 and 36 are objected to because of the following informalities: typically the first occurrence of a term is abbreviated and thereafter the abbreviation used. However, these claims first recite the abbreviation and then spell it out. It would be proper to in claim 22 use the abbreviation with the full spelling and thereafter use only the abbreviation for VEEV.
Claims 21-24 are drawn to a canceled claim. It is not clear to what the claims depend. For examination purposes, claims 21 and 22 and 24 are believed to depend from claim 13 and claim 23 from claim 22.
Claim 25 requires an article prior to “eukaryotic”. The host cell selections are independent limitations and therefore require their own article.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The dependent claims are included in the rejection because they fail to address or clarify the basis of the rejection as discussed in detail for the independent claims.
Claims 21-25 recite the limitation "claim 1". There is insufficient antecedent basis for this limitation in the claim. Claim 1 is cancelled. Hence, all the limitations in the claim are not proper.
Claim 22, 29-32 and 35 recite that the RNA is a modified alphavirus. However, this relationship is improper. The RNA cannot be an alphavirus. It appears applicants intend that the alphavirus RNA is from one of the provided for alphavirus.
Claim 36 recites the limitation "the modified alphavirus". There is insufficient antecedent basis for this limitation in the claim. Claim 33 recites a modified alphavirus replicon RNA which is not the same as a modified alphavirus.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 15, 16 and 26 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of producing a polypeptide of interest in vivo, the method comprising administering to the subject a nucleic acid molecule packaged in an alphavirus particle, the nucleic acid comprising a modified alphavirus replicon RNA, wherein the replicon RNA comprises a 5′-UTR of an alphavirus that is modified by a U to G nucleotide substitution at position 2 and sequences coding for biologically active alphavirus nonstructural proteins, and is devoid of at least a portion of viral structural protein coding sequences, and further comprises a nucleotide sequence encoding the polypeptide of interest wherein the nucleotide sequence is operably linked to a promoter, does not reasonably provide enablement for any other embodiment. 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 and use the invention commensurate in scope with these claims. This rejection is amended based upon applicants’ amendment.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of invention. The instant claims are drawn to a method of producing a polypeptide of interest in vivo wherein the nucleic acid molecule comprises a modified replicon RNA sequence. The modified replicon RNA comprises a 5’ UTR modified by mutation of the 2U to G. a sequence encoding a polypeptide and deletion of at least a portion of a sequence comprising the structural protein coding sequence.
2) Scope of the invention. The scope of the invention is broad in that the method is drawn to production of any polypeptide of interest in any subject with a replicon RNA.
3) Number of working examples and guidance. The specification teaches only one embodiment of the claimed replicon. VEEV replicon DNA was mutated to modify the U2 to a G. The replicons also expressed reporter genes. The modification did not affect the biologic activity of the replicon as measured by expression of the reporter gene. This results was said to be contrary to previous experimental results. The reporter gene expression was enhanced 2-3 fold. The reporter genes replace one of the structural genes according to future designs. There are no means of expressing any sequences in vivo.
4) State of the art. Alphavirus are enveloped viruses with positive strand RNA genomes which have been modified to delete the structural genes with genes of interest and as such are called replicons. AV have been developed mostly as vaccines but
5) Unpredictability of the art. The remaining issue with the claims is the lack of predictability of the means of nucleic acid delivered to a subject surviving long enough for the peptide to be produced. The ability to express a polypeptide in a subject comprises steps of delivery that have proved complicated. Kaczmarek teaches, page 2, col 1.
Naked, single-stranded RNA is prone to nuclease degradation, can activate the immune system, and is too large and negatively charged to passively cross the cell membrane—and must, therefore, be provided with additional means of cellular entry and escape from endosomes, which transport extracellular nanoparticles into the cytoplasm [10]. As such, the nucleic acid delivery field has centered on the design of delivery methods and materials that will transport RNA drugs to the site of interest
Schott et al teach,
Synthetic RNA can be generated in vitro, purified and subsequently introduced into target cells. This approach provides maximum safety, with no expression or cotransfer of potentially immunogenic or harmful viral components. However, naked RNA may be degraded by extracellular ribonucleases prior to reaching the cytosol of target cells,11 thus requiring protection through formulation with synthetic vehicles for many applications. Furthermore, distinct cell types may be partially or completely refractory to physicochemical delivery modes, lowering overall efficiency. Thus, viral transfer of nonviral RNA has recently emerged as an attractive alternative.13,14
It is not clear how applicants can provide for the means to overcome this issue with the claimed invention.
6) Amount of Experimentation Required. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention. The invention recites use of a broad group of sequence. Given the unpredictability of the art, the poorly developed state of the art with regard to predicting the structural/ functional characteristics of antagonists, the lack of adequate working examples and the lack of guidance provided by applicants, the skilled artisan would have to have conducted undue, unpredictable experimentation to practice the claimed invention.”
Consequently, the prior art (and post-filing art) when combined with the lack of any disclosed direct experimental test of Applicant's hypothesis, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed sequences could be identified given the lack of details necessary to identify those meeting the necessary functions. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970);and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 13, 15, 16, 21-23, 25-30 and 31-36 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-24 of U.S. Patent 11,083,786 and 1-24 of U.S. Patent 11,826,416. This rejection is maintained for reasons below.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1-24 of U.S. Patent 11,083,786 and of U.S. Patent 11,826,416. That is, the cited claims of U.S. Patent 11,083,786 and of U.S. Patent 11,826,416 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, U.S. Patent 11,083,786 is drawn to methods of inducing an immune response that requires methods of producing a polypeptide using a replicon with a modified 5’ UTR that is part of the AV family i.e. VEEV and expresses only nsp3 and an antigen. U.S. Patent 11,826,416 recites a structure for which the instant claims have overlap wherein the disclosure teaches that the vaccine compositions can be used in vitro to produce peptides (see col 12).
The claims as amended require a U2G substitution. The copending claims recite U.S.
U.S. Patent 11,083,786
5. The method of claim 1, wherein at least one of the first and second RNA replicons comprises a modified 5′-UTR with one or more nucleotide substitutions at position 1, 2, 4, or a combination thereof.
6. The method of claim 5, wherein at least one of the one or more nucleotide substitutions is a nucleotide substitution at position 2 of the modified 5′-UTR.
7. The method of claim 6, wherein the nucleotide substitution at position 2 of the modified 5′-UTR is a U>G substitution.
(related U.S. Patent 11,826,416)
8. The combination of claim 2, wherein at least one of the first and second RNA replicons comprises a modified 5′-UTR with one or more nucleotide substitutions at position 1, 2, 4, or a combination thereof. To this end the disclosure is limited in detail to the same U2G substitution claimed in U.S. Patent 11,083,786. One would conclude from the disclosure that this is the substitution intended in the claimed.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the U.S. Patent 11,083,786 and of U.S. Patent 11,826,416, then two different assignees would hold a patent to the claimed invention of U.S. Patent 11,083,786 and of U.S. Patent 11,826,416, and thus improperly there would be possible harassment by multiple assignees.
Conclusion
Claim 37 is objected to as dependent on a rejected claim but would be found allowable if drafted into independent form.
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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached on 8 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARIA MARVICH/Primary Examiner, Art Unit 1633