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 .
DETAILED ACTION
Priority
This application is a continuation of U.S. Application No. 17/818,314, filed August 8, 2022, now U.S. Patent No. 12,060,568, which is a divisional of U.S. Application No. 17/404,901, filed August 17, 2021, now U.S. Patent No. 11,421,248, which is a continuation of International Application No. PCT/US2020/067506, filed December 30, 2020, which claims the benefit of U.S. Provisional Application No. 62/992,700, filed March 20, 2020, and U.S. Provisional Application No. 62/955,801, filed December 31, 2019 that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 07/10/2024 is acknowledged. Claims 1-20 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
Drawings
The drawing filed on 07/10/2024 are acknowledged and accepted by the Examiner.
Claim Objections
Claims 12-15 and 19-20 are objected to for the following informalities:
Claims 12-15 and 19-20 are objected to as being dependent upon a rejected claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-11 and 17-18 are rejected under 35 U.S.C. 103(a) as being unpatentable over Renner et al. “Renner” (US PGPUB 2006/0024788, IDS of record dated 09/24/2024) in view of Tani et al. “Tani” (US PGPUB 20100203027, IDS of record dated 09/24/2024).
The claims are directed to a method for expressing a protein in a mammalian subject, comprising: administering an effective amount of a composition to the mammalian subject by intradermal injection to express the protein in the mammalian subject, wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent), wherein the ts-agent is a temperature-sensitive self-replicating RNA encoding the protein and comprising a viral replicon lacking a viral structural protein coding region, wherein the RNA is not packaged in a viral particle, wherein the ts-agent is capable of expressing the protein at a higher level at a permissive temperature from 31°C to 35°C than at a non-permissive temperate of 37°C ± 0.5°C, and wherein the protein is heterologous to the viral replicon.
Regarding claims 1-4, 10 and 17, Renner discloses “The invention is further directed to inducible gene expression systems employing alphavirus DNA vectors to create stable cell lines carrying genes encoding a non-cytopathic, temperature-sensitive, viral non-structural replicase protein. For example, the activity of the temperature-sensitive replicase used in the Examples, set out below, is switched on by reducing the temperature of the transfected cells from a temperature of 37° C. to a temperature lower than 34° C.” (see paragraph [0068]) and “Examples of alphaviruses include Aura virus, Bebaru virus, Cabassou virus, Chikungunya virus, Easter equine encephalomyelitis virus, Fort morgan virus, Getah virus, Kyzylagach virus, Mayoaro virus, Middleburg virus, Mucambo virus, Ndumu virus, Pixuna virus, Tonate virus, Triniti virus, Una virus, Western equine encephalomyelitis virus, Whataroa virus, Sindbis virus (SIN), Semliki forest virus (SFV), Venezuelan equine encephalomyelitis virus (VEE), and Ross River virus” (see paragraph [0079]) (instant claims 1-4,10-“ not Zscan”). Renner discloses an immunogenic composition for stimulating an immune response against a pathogen in a subject (The invention further provides pharmaceutical compositions,... The administration of these pharmaceutical compositions may, for example, result in expression of a polypeptide in tissues of an animal which is immunogenic and intended to function as a vaccination, Para. [0163]), comprising an excipient (comprising... a physiologically acceptable carrier, Para. [0163]; Components of compositions for administration include... non-aqueous solutions and suspensions. Examples of non-aqueous solvents are propylene glycol, Para. (0166)) and a temperature-sensitive agent (ts-agent} (comprising polynucleotides of the invention in solution, Para. [0163] More specifically, the present invention provides polynucleotides and methods whish allow precise regulation of the amount of specific RNA molecules produced in stably transfected recombinant host cells. This precise regulation results from the use of a temperature-sensitive RNA-dependent RNA polymerase (i.e., a replicase} which only replicates RNA molecules, to form new RNA molecules, at permissive temperatures, Para,[(0027]), wherein the ts-agent is a temperature-sensitive viral vector or a temperature-sensitive self-replicating RNA encoding an antigen of the pathogen (A wide variety of nucleotide sequences of interest can be expressed by the gene expression system of the invention. These sequences include, but are not limited to, sequences encoding... antigens which stimulate immune responses, Para. [0114], Heterologous sequences expressed by the vectors of the invention can encode proteins and RNA molecules from non-human species (e.g., other... viruses), Para. ((0120)) (instant claim 17), and wherein the ts-agent is capable of expressing the antigen at a permissive temperature but not at a non-permissive temperature (This precise regulation results from the use of a temperature-sensitive RNA-dependent RNA polymerase (i.e. a replicase) which only replicates RNA molecules, to form new RNA molecules, at permissive temperatures, Para. (0027): in one aspect, the present invention provides methods for producing polypeptides and RNA molecules comprising introducing nucleic acid molecules of the invention into recombinant host cells and incubating these cells at a permissive temperature, Para. [0135]). Further, Renner discloses “ORFs encoding the viral proteins contained in a vector, and ORFs of other foreign genes are arranged in the antisense direction in the genomic RNA via the above-described E-1-S sequence. The ORF closest to the 3′-end of the genomic RNA requires only an S sequence between the 3′-leader region and the ORF, and does not require an E or I sequence.
Renner does not explicitly teach wherein the RNA is not packaged in a viral particle.
However, Tani discloses wherein the RNA is not packaged in a viral particle and states “the ORF closest to the 5′-end of the genomic RNA requires only an E sequence between the 5′-trailer region and the ORF, and does not require an I or S sequence. Furthermore, two ORFs can be transcribed as a single cistron, for example, by using an internal ribosome entry site (IRES) sequence. In such a case, an E-1-S sequence is not required between these two ORFs. For example, in wild type paramyxoviruses, a typical RNA genome includes a 3′-leader region, six ORFs encoding the N, P, M, F, HN, and L proteins in the antisense direction in this order, and a 5′-trailer region on the other end. The orientation of the viral gene in the genomic RNAs of the present invention is not restricted. For example, similarly to the wild-type viruses, ORFs encoding the N, P, M, F, HN, and L proteins can be arranged after the 3′-leader region and before the 5′-trailer region. Certain types of viruses have different viral genes, but even in such cases, it is possible to arrange each gene as in the wild type, as described above. In general, vectors maintaining the N, P, and L genes can autonomously express genes from the RNA genome in cells and the genomic RNA is replicated. Furthermore, by the action of genes such as the F and HN genes which encode envelope proteins and the M gene, infectious virions are formed and released to the outside of the cells. Thus, such vectors become transmissible viral vectors. A cytokine gene to be carried by the vectors may be inserted into a non-protein-coding region in this genome, as described below. Viral vectors of the present invention encode cytokine genes in their genomic RNA. A recombinant viral vector harboring a cytokine gene is obtained by inserting a cytokine gene into an above-described viral vector genome. The cytokine gene can be inserted at any desired position in a non-protein-coding region of the virus genome, for example. The above nucleic acid can be inserted, for example, between the 3′-leader region and the viral protein ORF closest to the 3′-end; between each of the viral protein ORFs; and/or between the viral protein ORF closest to the 5′-end and the 5′-trailer region in genomic DNA. Furthermore, in genomes deficient in the F or HN gene or such, nucleic acids encoding the cytokine genes can be inserted into those deficient regions. When introducing a foreign gene into a paramyxovirus, it is desirable to insert the gene such that the chain length of the polynucleotide to be inserted into the genome will be a multiple of six (Journal of Virology, Vol. 67, No. 8, 4822-4830, 1993). An E-1-S sequence should be arranged between the inserted cytokine gene and the viral ORF. Two or more foreign genes can be inserted in tandem via E-1-S sequences (Para [0076] and [0077]).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method for expressing a protein in a mammalian subject as disclosed by Renner, whereby the RNA is not packaged in a viral particle given the teachings of Tani. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the purpose of using a viral vector effective for improving the expression of exogenous proteins in mammalian cells in a controlled and temperature-sensitive system.
Regarding claims 6 and 18, Renner discloses wherein the permissive temperature is from 30oC to 36oC, or 31oC to 35oC, or 32oC to 34oC, or 33oC + 0.5oC (Thus, the permissive temperature for the replicase activity encoded by the vector are below 34oC, and include temperatures from 30-33oC (Para [0106]) and the non-permissive temperature is 37oC + 0.5oC (Para [0148]). Renner also discloses the ts-agent comprises a nonstructural protein wherein the pharmaceutical agent is selected from the group consisting of a non-coding RNA, a siRNA, a shRNA, and an endonuclease editing system (in another aspect, the invention provides DNA molecules comprising polynucleotides which encode RNA molecules comprising... (co) at least one second nucleotide sequence which encodes one of the following:... (ii) a sequence encoding an untranslated RNA molecule (e.g., an antisense RNA molecule) (Para. [0029]-([0032]).
Regarding claims 5 and 9, Renner discloses embodiments whereby lipid nanoparticles are not utilized in the composition (see Examples).
Regarding claims 7-8, Renner discloses wherein the viral vector is selected from the group consisting of an alphavirus to create stable cell lines carrying genes encoding a non-cytopathic, ts, viral non-structural replicase protein (Para. [0068]) including Sindbis virus (SIN), Semliki forest virus (SFV), Venezuelan equine encephalomyelitis virus (VEE) (Para. [0070]).
Regarding claim 11, Renner discloses a chimeric antigen receptor (CAR) by stating “Fusion proteins also include proteins which have domains or regions derived from various different proteins. Examples of such a fusion protein are those containing domain II of Pseudomonas exotoxin, a domain or amino acid sequence which has binding affinity for a cell surface receptor associated with a particular cell type, and another amino acid sequence with a preselected biological activity. Domain II of Pseudomonas exotoxin will translocate across cell membranes. Using this system, fusion proteins can be designed which will bind to specific cells types, will translocate across the cytoplasmic membranes of these cells, and will catalyze predetermined intracellular biological reactions” (Para. [0123]). Therefore, the claimed invention would have been prima facie obvious to one or ordinary skill in the art before the effective filing date of the claimed invention.
Claim 16 is rejected under 35 U.S.C. 103(a) as being unpatentable over Renner et al. “Renner” (US PGPUB 2006/0024788, IDS of record dated 09/24/2024) in view of Tani et al. “Tani” (US PGPUB 20100203027, IDS of record dated 09/24/2024) as applied to claim 6 above, and further in view of Ban et al. “Ban” (US PGPUB 2016/0215270, IDS of record dated 09/24/2024). The teachings of Renner and Tani are outlined above and incorporated herein.
Regarding claim 16, Renner discloses an immunogenic composition for stimulating an immune response against an antigen in a mammalian subject, comprising an excipient and a temperature-sensitive agent (ts-agent) encoding the antigen.
Renner does not explicitly teach wherein the ts-agent is a Sendai viral vector.
Tani, however, discloses the use of viral vectors for gene therapy (see Abstract) and “that the gene transfer method could be simplified, and a superior protective effect could be produced in vivo by using negative-strand RNA virus vectors, in particular, Sendai virus-based vectors” (see paragraph [0016]). Moreover, Tani demonstrates Sendai virus vectors having temperature-sensitive mutations (see Drawings and Figures 3 and 4). In further view of Ban, who teaches using a temperature-sensitive Sendai virus (The present inventors conducted dedicated research on methods that can induce pluripotent stem cells with high efficiency, by using a temperature-sensitive Sandal virus vector and not culturing at a low temperature after vector introduction, Para. (0024)).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Renner with the teaching of Tani and Ban. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the purpose of using a viral vector effective for expressing exogenous proteins in human cells and given the knowledge that Tani and Ban demonstrate the successful expression of proteins into cells of interest, whereby the “Sendai virus (SeV) vectors are cytoplasmic viral vectors with all steps of their expression carried out within the cytoplasm. Thus, even when the vectors are used in vivo, there is no worry that a carried gene will become integrated into the host chromosome and cause genetic toxicity. Furthermore, these vectors have a number of excellent characteristics, such as high efficiency of gene transfer and expression both in vitro and in vivo, and long-term sustained expression in vitro. Thus, SeV is expected to have many applications and uses as a gene transfer vector in gene therapy, gene vaccination, antibody production” (see paragraph [0005] of Tani). Therefore, the claimed invention would have been prima facie obvious to one or ordinary skill in the art before the effective filing date of the claimed 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 Langi, 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.
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Claims 1-4 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6 and 8 of U.S. Patent No. 11/421,248. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another.
The claims are directed to a method for expressing a protein in a mammalian subject, comprising: administering an effective amount of a composition to the mammalian subject by intradermal injection to express the protein in the mammalian subject, wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent), wherein the ts-agent is a temperature-sensitive self-replicating RNA encoding the protein and comprising a viral replicon lacking a viral structural protein coding region, wherein the RNA is not packaged in a viral particle, wherein the ts-agent is capable of expressing the protein at a higher level at a permissive temperature from 31°C to 35°C than at a non-permissive temperate of 37°C ± 0.5°C, and wherein the protein is heterologous to the viral replicon.
The patented claims are directed to:
1. A composition for stimulating an immune response against an antigen in a mammalian subject, comprising an excipient and a temperature-sensitive agent (ts-agent) encoding the antigen, wherein the ts-agent is a temperature-sensitive Sendai viral vector, and wherein the ts-agent is capable of expressing the antigen at a permissive temperature but not at a non-permissive temperature, and the antigen is a spike protein or fragment thereof of a coronavirus (instant claim 1).
3. The composition of claim 1, wherein the permissive temperature is from 31° C. to 35° C., and the non-permissive temperature is 37° C.±0.5° C. (instant claims 1 and 6).
4. A composition for stimulating an immune response against an antigen in a mammalian subject, comprising an excipient and a temperature-sensitive agent (ts-agent) encoding the antigen, wherein the ts-agent is a temperature-sensitive self-replicating RNA comprising an Alphavirus replicon lacking a viral structural protein coding region, and wherein the ts-agent is capable of expressing the antigen at a permissive temperature but not at a non-permissive temperature, and the antigen is a spike protein or fragment thereof of a coronavirus (instant claim 1).
5. The composition of claim 4, wherein the Alphavirus is selected from the group consisting of a Venezuelan equine encephalitis virus, a Sindbis virus, and a Semliki Forrest virus (instant claims 2-4).
6. The composition of claim 4, wherein the Alphavirus is a Venezuelan equine encephalitis virus (instant claim 4).
8. The composition of claim 4, wherein the permissive temperature is from 31° C. to 35° C., and the non-permissive temperature is 37° C.±0.5° C (instant claim 6).
There is no patentable difference between the claimed methods and compositions and the patented composition in that the U.S. Patent No. 11/421,248 discloses a method for expressing a protein in a mammalian subject, comprising: administering an effective amount of a composition to the mammalian subject by intradermal injection to express the protein in the mammalian subject, wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent), wherein the ts-agent is a temperature-sensitive self-replicating RNA encoding the protein. Further, the compositions of ‘248 would anticipate the compositions herein.
Claims 1-5, 9 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-10 and 13-15 of U.S. Patent No. 12/060,568. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another.
The claims are directed to a method for expressing a protein in a mammalian subject, comprising: administering an effective amount of a composition to the mammalian subject by intradermal injection to express the protein in the mammalian subject, wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent), wherein the ts-agent is a temperature-sensitive self-replicating RNA encoding the protein and comprising a viral replicon lacking a viral structural protein coding region, wherein the RNA is not packaged in a viral particle, wherein the ts-agent is capable of expressing the protein at a higher level at a permissive temperature from 31°C to 35°C than at a non-permissive temperate of 37°C ± 0.5°C, and wherein the protein is heterologous to the viral replicon.
The patented claims are directed to:
1. A method for stimulating an immune response against an antigen in a mammalian subject, comprising:
administering an effective amount of a composition to the mammalian subject by intradermal injection to stimulate an immune response against the antigen in the mammalian subject,
wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent) encoding the antigen, the ts-agent is a temperature-sensitive viral vector, the ts-agent is capable of expressing the antigen at skin temperature of the subject but not at core temperature of the subject, and the antigen is a spike protein or fragment thereof of a coronavirus (instant claim 1).
2. The method of claim 1, wherein the viral vector is a Sendai viral vector (instant claim 16).
6. The method of claim 1, wherein the composition does not comprise lipid nanoparticles (instant claim 9).
7. A method for stimulating an immune response against an antigen in a mammalian subject, comprising:
administering an effective amount of a composition to the mammalian subject by intradermal injection to stimulate an immune response against the antigen in the mammalian subject, wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent) encoding the antigen, the ts-agent is a temperature-sensitive self-replicating RNA comprising a viral replicon lacking a viral structural protein coding region, the RNA is not packaged in a viral particle, and the ts-agent is capable of expressing the antigen at skin temperature of the subject but not at core temperature of the subject (instant claim 1).
8. The method of claim 7, wherein the replicon is an Alphavirus replicon (instant claim 2).
9. The method of claim 8, wherein the Alphavirus is selected from the group consisting of a Venezuelan equine encephalitis virus, a Sindbis virus, and a Semliki Forrest virus (instant claim 3).
10. The method of claim 8, wherein the Alphavirus is a Venezuelan equine encephalitis virus (instant claim 4).
13. The method of claim 7, wherein the core temperature of the subject is 37° C.±0.5° C (instant claim 1).
14. The method of claim 13, wherein the skin temperature of the subject is from 31° C. to 35° C (instant claim 1).
15. The method of claim 7, wherein the composition does not comprise lipid nanoparticles (instant claim 5).
There is no patentable difference between the claimed methods and compositions and the patented composition in that the U.S. Patent No. 12/060,568 discloses a method for expressing a protein in a mammalian subject, comprising: administering an effective amount of a composition to the mammalian subject by intradermal injection to express the protein in the mammalian subject, wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent), wherein the ts-agent is a temperature-sensitive self-replicating RNA encoding the protein. Further, the compositions of ‘568 would anticipate the compositions herein.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672
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