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 .
2. The Amendment filed on April 17, 2026, has been received and entered.
Claim Disposition
3. Claims 2-3, 9-23, 25-43, 45-47, 49, 51-99, 101-102 and 104-105 are cancelled. Claims 1, 4-8, 24, 44, 48, 50, 100 and 103 are pending. Claims 1, 4, 7-8 and 24 are under examination. Claims 5-6, 44, 48, 50, 100 and 103 are withdrawn from further consideration pursuant to 37 CFR 1.12(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim. The species SALL1 has been rejoined with SUDS3, however, other repressor domains and NIPPI repressor domains are withdrawn. Applicant is reminded to provide a complete list of claims with the appropriate status identifiers, note that claims 92-98 are not present and is construed as cancelled.
Information Disclosure Statement
4. The Information Disclosure Statement filed on April 17, 2026, has been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action. Note that references are stroke out due to improper date or citation.
Claim objection
5. Claims 1, 4, 7-8 and 24 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to spell out the meaning of the acronyms. See also claim 4 with similar issues. The dependent claims hereto are also included.
Appropriate correction is required.
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.
6. Claims 1, 4, 7-8 and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), 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.
The claimed invention is directed to a Cas fusion protein comprising a Cas protein and a SUDS3 repressor domain, wherein the Cas protein targets DNA. The claimed invention is not adequately described because there is no structure-function correlation. The claimed invention in claim 1 is devoid of any structural and functional limitations and note that claim 7 recites that the Cas protein is catalytically inactive. The invention as claimed encompasses a board variable genus of structures with no alignment of an activity. The invention as disclosed does not demonstrate possession of the entire genus. The specification discloses that the claimed invention involves transcriptional repression. It is noted that claim 24 recites a structure for the repressor domains, however no structure is found in claim 1 which needs to stand on its own. In addition, no specific Cas protein is provided. The specification discloses that “examples of Cas proteins include but are not limited to: Casl, CaslB, Cas2, Cas3,Cas4, Cass,CasSe (CasD), Cas6,Cas6e, Cas6f, Cas7, Cas8al,Cas8a2, Cas8b, Cas8c, Cas9 (Csnl or Csx12), CaslO,CaslOd, Cas12a, Cas12b, Cas12c, Cas12d, Cas12e, Cas12f, Cas12h, Cas12i, Cas12j, Mad7, CasX, CasY,Cas 13a,Cas14, C2cl,C2c2, C2c3, CasF, CasG,CasH,Csyl, Csy2, Csy3, Csel (CasA), Cse2 (CasB), Cse3 (CasE), Cse4 (CasC), Cscl, Csc2, Csa5,Csn2, Csm2, Csm3, Csm4, Csm5,Csm6, Cmrl, Cmr3, Cmr4, Cmr5,Cmr6, Csbl, Csb2, Csb3, Csx17, Csx14, CsxlO,Csx16, CsaX, Csx3, Csxl,Csx15, Csfl, Csf2, Csf3, Csf4, and Cul966, and homologs or modified versions thereof”(see paragraph [75]). It is also disclosed at paragraph [77] that, “modified versions of Cas proteins that may be used in the present invention, include but are not limited to catalytically inactive versions such as dCas9 and dCas12 or versions that have modified attenuated catalytic activity to provide a nicking function such as the nickase nCas9”. Note that claim 1 is not limited to any of this disclosure. Thus, the claimed invention is not commensurate in scope with the disclosure and no correlation is made between structure and function. Moreover note that the claimed invention is directed to a Cas fusion protein with a SUDS3 repressor domain that has fragments, which encompasses a large variable genus of structures that are not adequately described.
The specification fails to provide a representative number of species for the claimed genus to show that 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.
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "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. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 103
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.
7. 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.
8. Claim(s) 1, 4, 7-8 and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Broad Institute Inc. ((hereafter Broad), of record in the application) in view of Gearing (CRISPR 101: Cas 9 Nickase Design &Homology ), Kwon et al. (Nature Communication), US Patent No. 8586006, Aug 2007 (alignment, below ) and Reint et al. (eLife, 2021).
The reference teaches a Cas fusion protein comprising a Cas protein and one or both of a SALL1 repressor domain and a SUDS3 repressor domain (Abstract- The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, (claim 11-‘The composition of claim 4, wherein the adaptor protein and the functional domain, the linker optionally including a GlySer linker, (paragraph [0088])-The activated CRISPR enzyme may have associated (e.g. via fusion protein) one or more functional domains, like for example as described herein for the modified sgRNA adaptor proteins, (including for example, one or more domains from methylase activity, demethylase activity, transcription activation activity, transcription repression activity, (paragraph [0539]-In some embodiment, the functional domain may be a HDAC Recruiter Effector Domain. Preferred examples include those in the Table below, namely MeCP2, MBD2b, Sin3a, NcoR, Sall1, RCOR1. With regard to claim 7 Broad teaches the Cas fusion protein is catalytically inactive (see paragraph [0036]-‘The invention provides a method for directing a CRISPR-Cas9 system, including but not limited to a dead Cas9 (dCas9)’. The teaching of Broad pertains to claims 1 and 7. The primary reference is silent on ‘nickase’, however, it is known in the art. Gearing teach that CRISPR nickase creates a single strand rather than a double stranded break (Cas9 nickase) which is advantageous, see abstract. Furthermore, Kwon et al. teach cas9 based histone deacetylase (HDAC). It is well established in the art the SUDS3 and HDACs work together as core components of the Sin3/HDAC corepressor complex, a crucial machinery for regulating gene expression (SUDS3 acts as the adaptor protein helping assemble the complex with SIN3A and recruiting HDAC enzymes to specific DNA regions, influencing cell growth, development and inflammation). Kwon on page 2 teaches modulation of gene expression by transfected dCas9-HDAC3 (a fusion protein with catalytically inactive Cas protein and repressor domain complex). In addition, the art is replete with references that teach structures that are at least 90% or more identical to SEQ ID NO:2, one such alignment is provided below, thus the structure is not novel and certainly obvious. Furthermore, Reint et al. teach genome editing using CRISPR-Cas9-POLD3 fusion (see abstract and page 1). It is well established in the art that SUDS3 is equivalent to SDS3 and POLD3.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious. The references are considered to be analogous art, thus motivation to combine exists. The cited references in combination teaches a Cas fusion protein comprising a Cas protein and a repressor that is SALL1 or SUDS3/POLD3 and renders obvious nickase, catalytically inactive and a structure at least 80% identical to SEQ ID NO:2.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
ALIGNMENT
RESULT 1
US-12-376-951A-29328
(NOTE: this sequence has 9 duplicates in the database searched.
See complete list at the end of this report)
Sequence 29328, US/12376951A
Patent No. 8586006
GENERAL INFORMATION
APPLICANT: HOOD, Leroy
APPLICANT: BECKMANN, M. Patricia
APPLICANT: JOHNSON, Richard
APPLICANT: MARELLI, Marcello
APPLICANT: LI, Xiaojun
TITLE OF INVENTION: ORGAN-SPECIFIC PROTEINS AND METHODS OF THEIR USE
FILE REFERENCE: 655652003300
CURRENT APPLICATION NUMBER: US/12/376,951A
CURRENT FILING DATE: 2011-12-20
PRIOR APPLICATION NUMBER: PCT/US2007/017868
PRIOR FILING DATE: 2007-08-09
PRIOR APPLICATION NUMBER: US 60/836,986
PRIOR FILING DATE: 2006-08-09
NUMBER OF SEQ ID NOS: 72689
SEQ ID NO 29328
LENGTH: 328
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1676; Length 328;
Best Local Similarity 100.0%;
Matches 328; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSAAGLLAPAPAQAGAPPAPEYYPEEDEELESAEDDERSCRGRESDEDTEDASETDLAKH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSAAGLLAPAPAQAGAPPAPEYYPEEDEELESAEDDERSCRGRESDEDTEDASETDLAKH 60
Qy 61 DEEDYVEMKEQMYQDKLASLKRQLQQLQEGTLQEYQKRMKKLDQQYKERIRNAELFLQLE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DEEDYVEMKEQMYQDKLASLKRQLQQLQEGTLQEYQKRMKKLDQQYKERIRNAELFLQLE 120
Qy 121 TEQVERNYIKEKKAAVKEFEDKKVELKENLIAELEEKKKMIENEKLTMELTGDSMEVKPI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TEQVERNYIKEKKAAVKEFEDKKVELKENLIAELEEKKKMIENEKLTMELTGDSMEVKPI 180
Qy 181 MTRKLRRRPNDPVPIPDKRRKPAPAQLNYLLTDEQIMEDLRTLNKLKSPKRPASPSSPEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 MTRKLRRRPNDPVPIPDKRRKPAPAQLNYLLTDEQIMEDLRTLNKLKSPKRPASPSSPEH 240
Qy 241 LPATPAESPAQRFEARIEDGKLYYDKRWYHKSQAIYLESKDNQKLSCVISSVGANEIWVR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LPATPAESPAQRFEARIEDGKLYYDKRWYHKSQAIYLESKDNQKLSCVISSVGANEIWVR 300
Qy 301 KTSDSTKMRIYLGQLQRGLFVIRRRSAA 328
||||||||||||||||||||||||||||
Db 301 KTSDSTKMRIYLGQLQRGLFVIRRRSAA 328
Response to Arguments
9. Applicant’s comments have been considered in full. Withdrawn objections/rejection will not be discussed herein as applicant’s comments are moot. Note that the rejections of record under 112 first paragraph and art rejection remains but have been altered to reflect amendments made to the claims. Applicant state that the claimed invention is adequately described and have been amended to recite “Cas protein targets DNA”, thus a structure-function correlation. However, there is not structural limitation in claim 1 (any Cas protein fused to any SUDS3 repressor domain). Note that said domain is any structure at least 90% identical to SEQ ID NO:2 in dependent claim 24, so no specific one recited in any of the claims. Therefore, the rejection remains and applicant’s arguments are not persuasive. Applicant traverses the art rejection and separately attacks the references when the combined teaching renders the claimed invention as obvious. Applicant states that SUDS3 is not taught, however, the claims remain very broad and the art produced a structure that meets the ‘at least 90% sequence identity” which would inherently have the asserted function. A functionally equivalent product is provided in the art which applicant agrees is an ortholog which demonstrates similarities. The rejection of record points out the relationship between the Sin3A and SUDS3 which reads on fragments, based on the breath of the claims “a SUDS3 repressor domain (no specific one is claimed). Thus the arguments presented are not deemed persuasive. The examiner would welcome a conversation to discuss and reduce the remaining issues.
Conclusion
10. No claims are presently allowable.
11. Applicant’s amendment necessitated the new/modified 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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.
/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
Prosecution Insights