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 .
Claims 1-14 are pending as originally filed, and are considered herein.
Formalities
The specification, as amended 5/26/23 is accepted.
The drawings of 4/17/23 are accepted.
The IDS filings of 4/17/23; 4/17/23; 12/20/23; and 8/27/24, have been considered, and signed off upon herein.
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 1-14 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.
As seen by Claims 13-14, the claims specifically embrace generic in vivo transfection and delivering to a generic subject.
The specification teaches that the disclosure relates to pharmaceutical/veterinary compositions for treating pathologies involving bacteria of the human microbiome, including inflammatory and autoimmune disease, cancers, infections or brain disorders. It is taught to induce or enhance inflammatory/auto-immune disease/cancer development. More specifically, it is proposed to modulate the microbiome to improve the efficacy of immunotherapy, for example on CAR T cells/ TILs, and Tregs. Modulation of of the microbiome composition to improve immunotherapy may also include immune checkpoint inhibitors, e.g., PD1, PD-L1, and CTLA-4. Additionally, they may secrete molecules that will affect the brain. (paragraphs 165-170). It is also taught to use therapeutic compounds for vaccines, the compounds being made in the bacteria and providing prophylactic or therapeutic vaccination (paragraph 171). Non-therapeutic use is taught for cosmetic use, or for improving the well being of a subject not suffering a disease (Paragraph 172). There is no specific teaching of a specific compound, even one, that provides any of these, supposedly beneficial effects (it is noted that it is not clear how increasing inflammation/auto-immune disease or cancer development is any way beneficial). Without even one fleshed out example, the Artisan is left to the art to find the embodiments for the various diseases. For example, how does increasing autoimmune disease treat lupus, and how does a bacteria in the gut do so, even if it expresses antigenic proteins? The gut has a large range of immunogenic proteins, and yet no autoimmune disease is produced here. The system is designed to not be affected by immunogenic proteins, as part of the digestive system.
The Art was not mature enough at the time of invention to know which genes to utilize to transfect which bacteria and which part of the gut to do so, to have an effect. For example, Landry, et al. (2017) “Engineering Diagnostic and Therapeutic Gut Bacteria”, 5(5): article 10.1128, 30 pages long, teaches that an approach is need to design “smart probiotics that can diagnose or treat disease (e.g., ABSTRACT). While proposing various approaches throughout the disclosure (e.g., section “Engineering Smart Probiotics”), it is also recognized that testing of the bacteria is slow and expensive and so much work needs to be done up front (section “Experimental validation”. In the end, in the “OUTLOOK” it states that advances will enable creation of the “first smart probiotics”, implicitly admitting that there is none yet.
Thus, given the wide range of diseases, a lack of understanding how increasing inflammation/autoimmune disease/cancer development would treat a subject, the lack of any described embodiments, and given the wide range of possible proteins that may be expressed due to the genetic modification of the microbiome, the Artisan would not have understood Applicant to have been in possession of the invention as presently claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,661,443. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1: Patent claim 1 teaches a nucleic acid encoding an RBP of the same structure and Claim 2 further provides the scope of the different RBP.
Claim 2: Patent Claim 3 teaches C terminal portion is from any bacteriophage or bacteriocin.
Claim 3: Patent Claim 4 teaches the N-term fused at the same portions of the N-terminal RBP.
Claim 4: Patent Claim 5 teaches the same fusion region identities for the same sequence identifiers.
Claim 5: Patent Claim 6 contains the same sequence identifiers for the chimeric RBP.
Claim 6: Patent Claim 7 teaches the C-terminal domain having depolymerase activity against encapsuled bacterial strains.
While the patent does not claim delivering the vector into a target bacterial cell, the vector carrying a a nucleic acid payload of interest, it does teach vectors comprising sequences encoding the RBP, Cells comprising the nucleic acid, and cells comprising the vectors (e.g., Claims 9-11). On the other hand, the whole purpose of these vectors is to be used as bacterial delivery vehicle (e.g., TITLE; Col. 5).
Thus, at the time of invention, it would have been obvious to deliver a coding sequence of interest to a bacterial cell, as presently claimed. The Artisan would do so as the patent claims the subject matter taught for that specific purpose. The Artisan would expect success, as it is claimed subject matter and its essential written description for its patentable use.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,661,443 in view of Jiang, et al. (2013) “RNA-guided editing of bacterial genomes using CRISPR-Cas systems”, Nature Biotechnology, 31(3): 233-41.
As shown above, the patent makes obvious the base claims, however, the aspects of a nuclease targeting cleavage of a target bacterial cell genome in the bacteria is not specifically claimed/taught.
On the other hand, Jiang teaches editing bacterial genomes using CRISPR-Cas systems (e.g., TITLE), and by introduction of a targeting construct that kills wild-type cells, and the editing template that eliminates CRISPR interference and introduces the desired mutation(s) (conclusion), the bacteria, including S. Pneumoniae and E. coli may be so-treated to produce a protein where the non-edited cells are killed, meaning the edited cells express the desired protein that allows them to live, and thus, is therapeutic (e.g., abstract). Moreover, the RNA is another transgene required of the CRISPR system to edit the genome, and contains an antisense sequence (e.g., p. 233, col. 1, paragraph 1).
Thus, in light of the patent and the art, it would be obvious to make the invention. The Artisan would do so to express therapeutic genes in bacteria, saving them in a selection step. The Artisan would expect success, as the components are utilized for art-recognized purposes.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,512,116. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1: Patent Claim 1 teaches treating bacterial infection, by administering a composition comprising a chimeric RBP, of similar structure as presently claimed. Patent Claim 14 teaches reducing virulent/antibiotic resistant bacteria in population of the same, comprising delivery of a vehicle comprising RBPs of similar structure as presently claimed.
Claim 2: Patent Claim 2 teaches any bacteriophage or bacteriocin derived different RBP.
Claim 3: Patent Claim 3 teaches wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain within one of the amino acid regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP.
Claim 4: Patent Claim 4 teaches wherein the N-terminal domain and the C-terminal domain are fused within said region at an insertion site having at least 80% identity with insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
Claim 5: Patent Claim 5 teaches wherein the chimeric RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 123-129, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246.
Claim 6: Patent Claim 6 teaches wherein the C-terminal domain of the different RBP has a depolymerase activity against an encapsulated bacterial strain.
Claim 7: Patent Claim 7 teaches wherein the bacterial delivery vehicle further comprises a nucleic acid payload encoding a protein of interest or a nucleic acid of interest.
Claim 8: Patent Claim 8 teaches wherein the nucleic acid of interest is selected from the group consisting of Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme, a TALEN, a ZFN, a meganuclease, a recombinase, a bacterial receptor gene, a membrane protein gene, a structural protein gene, a secreted protein gene, a gene expressing resistance to an antibiotic or to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any combination thereof.
Claim 9: Patent Claim 9 teaches wherein the enzyme is a nuclease or a kinase.
Claim 10: Patent Claim 10 teaches wherein the protein of interest is a nuclease that targets cleavage of a host bacterial cell genome or a host bacterial cell plasmid.
Claim 11: Patent Claim 22 teaches wherein the enzyme is a nuclease or a kinase.
Claim 12: Patent Claim 26 teaches an anti-sense molecule.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,236,133. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1: Patent Claim 1 is to RBPs of the same chimeric structure. Patent Claim 8 teaches bacterial delivery vehicles comprising the RBP. What is not taught is the method of transfecting cells by exposure to the vehicle.
On the other hand, it is also clear that the vehicles are specifically meant for delivery to bacteria, as further emphasized by the essential written description (e.g., TITLE) and claims showing the import of targeting bacteria (e.g., Patent Claim 8, bacterial delivery vehicles comprising the RBP).
Thus, it would be obvious to transfect bacteria with vehicles as presently claimed, as the patent teaches it through its essential written description of purpose. The Artisan would do so, and expect success, as it is part of the claims, and part of their essential written description provided for the claims.
Claim 2: Patent Claim 2 teaches wherein said different RBP is derived from any bacteriophage or bacteriocin.
Claim 3: Patent Claim 4 teaches wherein said N-terminal domain of the chimeric RBP is fused to said C-terminal domain within one of the amino acid regions selected from positions 80-150, 320-460, or 495-560 of the N-terminal RBP.
Claim 4: Patent Claim 5 teaches wherein the N-terminal domain and the C-terminal domain are fused within said region at an insertion site having at least 80% identity with insertion site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:248), ADAKKS (SEQ ID NO: 249), MDETNR (SEQ ID NO: 250), SASAAA (SEQ ID NO: 251), and GAGENS (SEQ ID NO: 252).
Claim 5: Patent Claim 6 teaches wherein the chimeric RBP comprises the amino acid sequence of SEQ ID NO: 2, 4, 7, 9, 12, 15, 17, 20, 23, 24, 25, 27, 29, 31, 33, 35, 37, 39, 41, 42, 44, 46, 47, 48, 49, 50, 51, 52, 53, 56, 59, 123-129, 130, 131, 132, 135, 138, 139, 142, 145, 148, 151, 216, 219, 221, 223, 227, 230, 232, 234, 236, 238, 240, 243, 245 or 246.
Claim 6: Patent Claim 7 teaches wherein the C-terminal domain of the different RBP has a depolymerase activity against an encapsulated bacterial strain.
Claim 7: Patent Claim 15 teaches further comprising a nucleic acid payload encoding a protein of interest or a nucleic acid of interest.
Claim 8: Patent Claim 16 teaches wherein the nucleic acid of interest is selected from the group consisting of a Cas nuclease gene, a Cas9 nuclease gene, a guide RNA, a CRISPR locus, a toxin gene, a gene expressing an enzyme such as a nuclease, a kinase, a TALEN, a ZFN, a meganuclease, or a recombinase, a bacterial receptor gene, a membrane protein gene, a structural protein gene, a secreted protein gene, a gene expressing resistance to an antibiotic or resistance to a drug in general, a gene expressing a toxic protein or a toxic factor, and a gene expressing a virulence protein or a virulence factor, or any combination thereof.
Claim 9: Patent Claims 16 and 17 teach nucleases.
Claim 10: Patent Claim 17 teaches wherein the protein of interest is a nuclease that targets cleavage of a host bacterial cell genome or a host bacterial cell plasmid
Claim 11: Patent Claim 19 teaches wherein the nucleic acid payload encodes a therapeutic protein.
Claim 12: Patent Claim 20 teaches wherein the nucleic acid payload encodes an anti-sense nucleic acid molecule.
Conclusion
No claim is allowed.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638