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. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 22, 2026, has been entered.
Claim Disposition
3. Claims 4 and 9-12 have been cancelled. Claims 1-3, 5-8 and 13-16 are pending. Claims 1 and 3 are under examination. Claims 2, 5-8 and 13-16 are withdrawn as directed to a non-elected invention.
Information Disclosure Statement
4. The Information Disclosure Statements filed on July 22, 2026 and April 8, 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. Some reference lined through as they represent an improper citation of the date.
Claim objection
5. Claims 1 and 3 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to read, “A complex, comprising:
a genome editing enzyme and a cell membrane-permeable peptide (CPP), …..wherein the CPP has 12 to 20 amino acid residues in length……,wherein the CPP is fused to the genome editing enzyme, wherein the CPP is ……wherein the CPP is a polyhistidine and wherein all of constituent…..”.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 and 3 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) contain 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 as amended is directed to ‘a complex comprising a fusion of a genome editing enzyme and a CPP (cell membrane permeable peptide)’. The claimed invention is not adequately defined and encompasses a large variable genus of structures encompassed in the claims with respect to the genome editing enzyme and CPP of 12-20 amino acids. No structure or activity per se. The claimed invention encompasses features such as a Cas family nuclease, a polyhistidine and wherein all of the constituent amino acid residues are histidine residues, however no reference structure is provided. Thus no correlation is made between structure and function.
The specification discloses that the genome editing enzyme can be from the Cas family nucleases such as Cas 9, Cas 12 etc. (see page 17). It is disclosed that the CPP can be a polyhistidine of 12 to 20 amino acids, however it is within a fusion and does not give a full glimpse of the entire structure claimed. The claimed invention is not limited to a specific embodiment. An ordinary skilled worker is not informed about the claimed complex and its components. The claims are not commensurate in scope with the disclosure in the specification. The specification also discloses that mutants are encompassed in the claimed invention but the claims are limited to any specific fusion partner. It is well established in the art that a single amino acid change can be detrimental to the structure-function relationship of the protein so much so that the protein can be rendered inactive or not functional in the manner asserted.
The claimed invention does not inform an ordinary skilled worker of the metes and bounds of the claims. There is also no clear structure-function correlation provided. The claimed invention is overly broad and encompasses large variable genus of enzymes. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. See Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir.1997). Thus, applicant has not demonstrated possession of the invention as claimed. Furthermore, the 'written description' requirement.., serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed ....The descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The purpose of the written description requirement "is to ensure that the scope of the right to exclude ... does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification." Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345-46 (Fed. Cir. 2000). The goal of the written description requirement is "to clearly convey the information that an applicant has invented the subject matter which is
claimed." In re Barker, 559 F.2d 588, 592 n.4 (CCPA 1977) "A disclosure in an application, to be complete, must contain such description and details as to enable any person skilled in the art or science to which the invention pertains to make and use the invention as of its filing date." In re Glass, 492 F.2d 1228, 1232 (CCPA 1974).
Additionally, 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 of structures, 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).
Accordingly, the claimed invention is determined as lacking adequate written description because applicant has not demonstrated possession of the entire genus encompassed in the claims which is vast with respect to the fusion protein that encompasses mutants and fragments with no asserted activity.
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.
7. Claims 1 and 3 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 and the dependent claims hereto are ambiguous with the recitation of a Cas family nuclease because it is unclear if that refers to Cas 9, Cas 12, Cas 13, Cas 3, Cas 4 etc., and they are all specialized.
.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. Claim(s) 1 and 3 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Liars et al. (US 10,851367, September 7, 2016).
The claimed invention is broadly directed to a complex comprising a genome editing enzyme fused to CPP wherein the enzyme is a Cas family nuclease and CPP is a polyhistidine with 12 to 20 amino acids, as such the reference is applied based on the breath of the claims.
Liars at paragraph (4) under the Background section discloses that, ‘in the context of gene therapy, most gene editing agents have often been delivered via plasmid DNA encapsulated in viral-derived vectors such as adeno viruses and adeno-associated viruses. Unfortunately, this type of approach has been plagued with serious issues for the patients mainly i) increased risk of insertional mutagenesis, ii) increased risks of hepatotoxicity upon interaction of viral vector with Kupffer cells and iii) only transient pharmacological benefit for the patient triggered by immunogenic response against the treated cells. As a result, there remains a need to find more effective and safer ways to deliver gene editing agents. Attempts thus far have been elusive and in this context, delivering gene editing agents in the form of the protein, and not its DNA or RNA, represent an immense therapeutic opportunity. At paragraph (14), it is disclosed that an aspect of Liars invention includes a method for editing a nucleic acid molecule encoding a protein associated with a liver disease or condition or a liver modulated disease or condition in a subject……” (see also paragraph 923, FIG. 4 and FIG. 5). Liars teach the usage of CRISPR-Cas nuclease, such as Cas 9 (see the Summary of Invention section, paragraphs (16)-(26)). The reference also teaches a histidine-rich peptide (see paragraph (96)) and teaches fusion proteins with Cas 9 (see paragraph (52)-(57), for example). Therefore, the limitations of the claims are met by the reference.
Response to Arguments
9. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that new rejections have been instituted for the reasons set forth above.
Conclusion
10. No claims are presently allowable.
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.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
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