CTNF 18/886,300 CTNF 77456 DETAILED ACTION 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claims 13-26 are pending and under consideration in this Office Action. Title 06-11 AIA The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 AIA Claim s 13-26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claim 13 recites the phrase “method of modulating transcription of an engineered expression construct” which renders the claim vague and indefinite since it is unclear if the system increases transcription of the engineered expression construct in mammalian cells or decreases transcription of the engineered expression construct in mammalian cells. Claim 13 recites the phrase “so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated” which renders the claim vague and indefinite since the phare “transitions from the first state to the second state” has not been defined and is not recited in the claim. Dependent claims 14-26 are also rejected because they do not correct the defects. Claim Rejections - 35 USC § 112 07-30-01 AIA The following is a quotation 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 35 U.S.C. 112 (pre-AIA), first paragraph: 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. 07-31-01 AIA Claim s 13-26 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. ?The claims are drawn to a broad and widely varying genus of methods of modulating transcription of any engineered expression construct comprising one to 12 zinc finger binding sites operably linked to any promoter and any coding sequence, the method comprising steps of: contacting a system comprising the engineered expression construct with any engineered mammalian transcription regulator protein comprising any regulator domain and a DNA-binding domain that transitions between a first, inactive state and a second, active state when a small molecule agent is present, wherein the DNA binding domain has exactly three active zinc fingers and binds to the zinc finger binding sites in the engineered expression construct, the regulator domain includes a domain selected from the group consisting of VP16, VP64, p65, HSF1, and RTA activation domains; and contacting the system with the any small molecule agent, so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated. According to MPEP 2163: “For each claim drawn to a genus: 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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 (see i)(C), above). See Eli Lilly , 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc ., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…” According to MPEP 2163.02: “The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar , 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc ., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow , 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).” The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; IDS filed 09/16/2024) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; IDS filed 09/16/2024) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). The reference teachings only provide guidance for searching and screening for the any engineered mammalian transcription regulator protein comprising the recited domains. The specification as originally filed does not disclose a representative number of species encompassed by the claimed genus by actual reduction to practice. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which amino acid sequences and structures correlate DNA binding, transcription activation, and/or transcription inhibition. Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants were in possession at the time the application was filed of the claimed genus of methods of modulating transcription of any engineered expression construct comprising one to 12 zinc finger binding sites operably linked to any promoter and any coding sequence, the method comprising steps of: contacting a system comprising the engineered expression construct with any engineered mammalian transcription regulator protein comprising any regulator domain and a DNA-binding domain that transitions between a first, inactive state and a second, active state when a small molecule agent is present, wherein the DNA binding domain has exactly three active zinc fingers and binds to the zinc finger binding sites in the engineered expression construct, the regulator domain includes a domain selected from the group consisting of VP16, VP64, p65, HSF1, and RTA activation domains; and contacting the system with the any small molecule agent, so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated . Claim Rejections - 35 USC § 103 07-20-aia AIA 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 of this title, 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. 07-20-02-aia AIA This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. ?. Claims 13-26 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. ("Activation domains for controlling plant gene expression using designed transcription factors". Plat Biotechnol J., 2013; 11(6), pp. 671-680; IDS filed 09/16/2024) in view of WO1996020951 (07/11/1996; IDS filed 09/16/2024), WO2013022739 (02/14/2013; IDS filed 09/16/2024), and US20030049842 (03/13/2003; PTO 892). Li et al. teach a transcription system comprising engineered protein that activates gene expression, the engineered protein comprising a DNA binding domain and a transcription activator domain (VP16) comprising zinc fingers, and expression vector comprising a minimal promoter and DNA binding site (ZFP site) for the DNA binding domain of the engineered protein. See entire publication and abstract especially Figs. 1-3, Table 1, Results and discussion section, Experimental procedures section, pages 671-677. The teachings of the claims differ from the reference in that the reference does not teach the claimed method of modulating transcription of an engineered expression construct. WO1996020951 teaches an engineered protein that inhibits gene expression where the engineered protein comprises a DNA binding domain and a transcription inhibitor domain. WO1996020951 teaches a chimeric protein which (a) selectively binds a DNA sequence with a Kd value of about 10-8 or better, and (b) contains at least one composite DNA-binding region comprising a continuous polypeptide chain containing two or more component polypeptide domains, at least two of which are mutually heterologous, wherein at least one of the component polypeptide domains is a zinc finger domain. See entire publication and claims especially claims 1-30. WO2013022739 teaches an extracellular sensor comprising a ligand binding domain, a transmembrane domain, a protease domain, a protease cleavage site, and a transcription factor. WO2013022739 teaches a composition comprising: i) an exogenous extracellular sensor, and/or ii) a nucleic acid sequence encoding said exogenous extracellular sensor, wherein said exogenous extracellular sensor comprises: a) a ligand binding domain, b) a transmembrane domain, c) a protease cleavage site, and d) a functional domain. See entire publication and claims especially claims 1-18 US20030049842 teaches transcriptional activators which differ in their activation potential by more than 3 orders of magnitude, where the transactivators are fusions between a DNA binding protein including a Tet repressor and minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). US20030049842 teaches substitution mutations at amino acid position 442 within the minimal VP16 domain provide transactivators with differing transactivation ability where chimeric activation domains comprising both wild type and mutant minimal VP16 domains provide additional variants with differing transactivation ability. US20030049842 teaches nucleic acid molecules, vectors, host cells, fusion proteins, transgenic and homologous recombinant organisms and methods of regulating gene transcription. See entire publication and all claims especially claims 1-11 and 16-27 and paragraphs [0005]- [0013] Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by using the Herpes simplex virus protein 16 (VP16) of US20030049842 as the transcription activator and/or regulator domain of the engineered protein comprising a transcription regulator domain; and modifying the system of Li et al. to comprise the engineered protein of Li et al. as the engineered protein that activates gene expression, the engineered protein of WO1996020951 as the engineered protein that inhibits gene expression, the engineered protein comprising the Herpes simplex virus protein 16 (VP16) of US20030049842 as the transcription activator and/or regulator domain, expression vector comprising a gene of interest that is expressed from the minimal promoter; and contacting the with a desired small molecule agent to activate transcription. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a transcription system comprising engineered proteins which can be used for studying expression and function of genes of interest in mammalian cells. It would have been obvious to modify and make the construct to comprise two or more zinc finger binding sites having the recited spacing, position of the zinc finger binding sites, comprise a minimal promoter having a TATA box and recited position to the zinc finger binding site as routine experimentation and/or as desired in view of the reference teachings. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because making engineered proteins comprising DNA binding domain and a transcription activator or inhibitor domain are known in the art as shown by the reference teachings. Hence, the claimed invention as a whole is prima facie obvious. Double Patenting 08-33 AIA 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp. Claims 13-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of US Patent 12091668. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. The claims and/or specification of the patent teach the claimed method of modulating transcription of an engineered expression construct comprising one to 12 zinc finger binding sites operably linked to a promoter and a coding sequence, the method comprising steps of: contacting a system comprising the engineered expression construct with an engineered mammalian transcription regulator protein comprising a regulator domain and a DNA-binding domain that transitions between a first, inactive state and a second, active state when a small molecule agent is present, wherein: the DNA binding domain has exactly three active zinc fingers and binds to the zinc finger binding sites in the engineered expression construct, the regulator domain includes a domain selected from the group consisting of VP16, VP64, p65, HSF1, and RTA activation domains; and contacting the system with the small molecule agent, so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated. Thus, the teachings anticipate the claimed invention. Claims 13-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of US Patent 9732392. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. The claims and/or specification of the patent teach the claimed method of modulating transcription of an engineered expression construct comprising one to 12 zinc finger binding sites operably linked to a promoter and a coding sequence, the method comprising steps of: contacting a system comprising the engineered expression construct with an engineered mammalian transcription regulator protein comprising a regulator domain and a DNA-binding domain that transitions between a first, inactive state and a second, active state when a small molecule agent is present, wherein: the DNA binding domain has exactly three active zinc fingers and binds to the zinc finger binding sites in the engineered expression construct, the regulator domain includes a domain selected from the group consisting of VP16, VP64, p65, HSF1, and RTA activation domains; and contacting the system with the small molecule agent, so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated. Thus, the teachings anticipate the claimed invention. Claims 13-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of US Patent 12410417. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. The claims and/or specification of the patent teach the claimed method of modulating transcription of an engineered expression construct comprising one to 12 zinc finger binding sites operably linked to a promoter and a coding sequence, the method comprising steps of: contacting a system comprising the engineered expression construct with an engineered mammalian transcription regulator protein comprising a regulator domain and a DNA-binding domain that transitions between a first, inactive state and a second, active state when a small molecule agent is present, wherein: the DNA binding domain has exactly three active zinc fingers and binds to the zinc finger binding sites in the engineered expression construct, the regulator domain includes a domain selected from the group consisting of VP16, VP64, p65, HSF1, and RTA activation domains; and contacting the system with the small molecule agent, so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated. Thus, the teachings anticipate the claimed invention. Claims 13-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of US Patent 12454689. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. The claims and/or specification of the patent teach the claimed method of modulating transcription of an engineered expression construct comprising one to 12 zinc finger binding sites operably linked to a promoter and a coding sequence, the method comprising steps of: contacting a system comprising the engineered expression construct with an engineered mammalian transcription regulator protein comprising a regulator domain and a DNA-binding domain that transitions between a first, inactive state and a second, active state when a small molecule agent is present, wherein: the DNA binding domain has exactly three active zinc fingers and binds to the zinc finger binding sites in the engineered expression construct, the regulator domain includes a domain selected from the group consisting of VP16, VP64, p65, HSF1, and RTA activation domains; and contacting the system with the small molecule agent, so that the engineered mammalian transcription regulator protein transitions from the first state to the second state and transcription of the engineered expression construct is activated. Thus, the teachings anticipate the claimed invention. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272 0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM-5:00PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on (408)918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652 Application/Control Number: 18/886,300 Page 2 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 3 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 4 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 5 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 6 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 7 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 8 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 9 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 10 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 11 Art Unit: 1652 18886300-000 Application/Control Number: 18/886,300 Page 12 Art Unit: 1652 18886300-000
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