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, 6-9, 11, 14, 16, 19, 23-26, 28, 31, 34, 36, 39, 43, and 44 are pending.
Election/Restrictions
Applicant’s election without traverse of Group III (claims 25, 26, 28, 31, 34, 36, and 39) in the reply filed on 07/29/2026 is acknowledged.
Claims 1, 6 – 9, 11, 14, 16, 19, and 44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/29/2026.
New claims 43 and 44 have been added. New claim 43 is drawn to the elected pharmaceutical composition of claim 25 and is under consideration. New claim 44 is drawn to a nonelected invention of Group I and is withdrawn from further consideration.
Claim 39 is under consideration as it is drawn to the elected pharmaceutical composition of claim 25. Claim 29 is not under consideration as it is cancelled and was listed as “29” instead of “39” in error in the Requirement for Restriction/Election mailed. 05/29/2026.
Claims 25, 26, 28, 31, 34, 36, 39, and 43 are under consideration.
Priority
This application claims foreign priority to CHINA PCT/CN2021/133681 filed 11/26/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/25/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings submitted on 05/21/2024 are acknowledged.
Specification
The use of the term Viromer and Quant-iT Ribogreen, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at para. 0179, 0208, and 0372. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 25 is objected to because of the following informalities: in line 2, “a least one” should read “at least one” to correct grammar. 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.
Claims 25, 26, 28, 31, 34, and 43 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.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly 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).
Claim 25 recites “or a portion thereof” in lines 9 and 10 and thus claim 25 is a genus claim that encompasses any portion of any of a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor.
Claim 28 recites “or a portion thereof” in line 2 – 3 and thus claim 28 is a genus claim that encompasses any portion of any DNA methyltransferase.
Claim 31 recites “or a portion thereof” in line 2 – 3 and thus claim 31 is a genus claim that encompasses any portion of any zinc-finger protein-based transcription factor.
Claim 34 recites “or a portion thereof” in line 2 and 3 and thus claim 34 is a genus claim that encompasses any portion of any DNA methyltransferase and any portion of any zinc finger protein-based transcription factor.
The instant specification fails to describe the entire genus of any portion of any of a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor. The genus for any portion of any of a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor is highly variant, inclusive to numerous sequences (nucleic acid and amino acid) where the sequence may be derived from any portion of a nucleic acid encoding a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor or where the sequence may be derived from any portion of the amino acid sequence of any DNA methyltransferase, a DNA demethylase, histone methyltransferase, histone demethylase, and zinc finger protein-based transcription factor. Thus, the genus of portions of , a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor which, when comprised in a pharmaceutical composition as claimed, lacks a written description, and as such, there is no indication that Applicants had possession of the claimed invention.
From the specification, it is clear that Applicants have possession of KRAB (SEQ ID NO: 22), a portion a zinc finger protein-based transcription factor (para. 036). However, the claims are not limited to SEQ ID NO: 22 because the claims only require a portion of a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor. The specification fails to teach or describe any other portion of any of a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor.
The specification lacks sufficient variety of species of portions of any of a DNA methyltransferase, a DNA demethylase, a histone methyltransferase, a histone demethylase, and a zinc finger protein-based transcription factor to reflect the variance in the genus since the specification provides only one example a portion of a zinc finger protein-based transcription factor that is SEQ ID NO: 22. The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad generics, with respect to all of the potential sequences that may “provide a modification of at least one nucleotide near the PCSK9 gene and/or within a PCSK9 regulatory element” as recited in claim 25. The possible portions of sequences are limitless with potentially thousands of sequences that may provide a modification of at least one nucleotide. The purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed by them. A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention."
In the instant case, the breadth of the genus of any portion of any of a zinc finger protein-based transcription factor, lacks a written description. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the specification is SEQ ID NO: 22. There is not even identification of any particular sequence required to provide a modification of at least one nucleotide. The skilled artisan cannot envision the detailed sequences that are encompassed by the claims, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited genus and subgenus. Thus, the written description requirement has not been satisfied.
Applicant is reminded that Vas-Cath makes clear that the written description of 35 U.S.C. 112 is severable from its enablement provision [see p. 1115].
Claim Rejections - 35 USC § 112
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.
Claims 25, 26, 28, 31, 34, 36, 39, and 43 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.
The term “near” of “near a PCSK9 gene” in claim 25 is a relative term which renders the claim indefinite. The term “near a PCSK9 gene” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The location of a genomic region is thus rendered indefinite by the use of “near a PCSK9 gene. Claims 26, 28, 31, 34, 36, 39, and 43 are also rejected as they depend from claim 25 and do not clarify the grounds of rejection.
The term “near” of “near the PCSK9 gene” in claim 43 is a relative term which renders the claim indefinite. The term “near the PCSK9 gene” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The location of a genomic region is thus rendered indefinite by the use of “near a PCSK9 gene.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 25, 26, 28, 31, 34, 36, 39, and 43 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Chen (US11434491-B2; Filed 10/19/2020; Published 09/06/2022), hereinafter Chen.
Claim 25 is drawn to a pharmaceutical composition comprising a fusion molecule comprising at least one DNA binding protein and at least one modulator of gene expression, or a nucleic acid sequence encoding the fusion molecule, wherein the fusion molecule is targeted to a genomic region near a PCSK9 gene and/or within a PCSK9 regulatory element, wherein the at least one modulator of gene expression provides a modification of at least one nucleotide near the PCSK9 gene and/or within a PCSK9 regulatory element, wherein the at least one modulator of gene expression comprises a DNA methyltransferase (DNMT), a DNA demethylase, a histone methyltransferase, a histone demethylase, or a portion thereof, or a zinc finger protein-based transcription factor or a portion thereof, or a combination thereof, and wherein the at least one DNA binding protein is a Cas9, dCas9, Cpf1, a zinc finger nuclease (ZNF), a transcription activator-like effector nuclease (TALEN), a homing endonuclease, a dCas9-FokI nuclease or a MegaTal nuclease.
Regarding claims 25, 26, 28, 31, 34, 36, and 43, Chen teaches a composition comprising a fusion molecule comprising dCas9 (“dCas9” of claim 25 and 36) fused to the KRAB domain (“a zinc finger protein-based transcription factor or a portion thereof” of claim 25, 31, 34) and fused to Dnmt3A-Dnmt3L (“DNMT” of claim 25 and 28; “DNA methyltransferase” of claim 34) (col. 51, lines 5 – 20; Figure 1A, 1B, 1D; Figure 5; col. 53, lines 10 – 67) (referred to as all-in-one protein or p76 (V1)). Chen teaches the composition comprises a plasmid encoding a sgRNA (SEQ ID NO: 44 and SEQ ID NO: 62) that is complementary to a DNA sequence near the PCSK9 gene and/or within the PCSK9 regulatory element of SEQ ID NO: 43 and SEQ ID NO: 61, respectively (“wherein the fusion molecules is targeted to a genomic region near a PCSK9 gene and/or within a PCSK9 regulatory element” of claim 25 and “sgRNA” of claim 43) for silencing of the PCSK9 gene (“provides a modification of at least one nucleotide near the PCSK9 gene and/or within a PCSK9 regulatory element” of claim 25) (col. 53, lines 20 – 45; Figure 4H; Table 3; col. 3, lines 54 – 57). SEQ ID NO: 61 is located within the promoter and 5’-UTR of the mouse Pcsk9 gene (“transcription start site” and “core promoter” claim 26) as evidenced by a BLAST search of Chen’s SEQ ID NO: 61 with the result shown below:
PNG
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289
1182
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Greyscale
Regarding claim 39, Chen teaches a fusion molecule that is the all-in-one protein variant p112 in Figure 5 comprising dCas9 fused with KRAB via HA and BFP on the C-terminal end and DNMT3A and DNMT3L on the N-terminal end that sustains gene silencing at a higher efficiency than the p76 (V1) design (col. 54, lines 35 – 60; col. 78, lines 11 – 21).
Therefore, Chen anticipates claims 25, 26, 28, 31, 34, 36, 39, and 43.
Claim(s) 25, 26, 31, 36 and 43 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Gersbach (WO2017180915-A2; Filed 04/13/2017; Published 10/19/2017), hereinafter Gersbach which is cited on the IDS filed 06/25/2024.
Claim 25 is drawn to a pharmaceutical composition comprising a fusion molecule comprising at least one DNA binding protein and at least one modulator of gene expression, or a nucleic acid sequence encoding the fusion molecule, wherein the fusion molecule is targeted to a genomic region near a PCSK9 gene and/or within a PCSK9 regulatory element, wherein the at least one modulator of gene expression provides a modification of at least one nucleotide near the PCSK9 gene and/or within a PCSK9 regulatory element, wherein the at least one modulator of gene expression comprises a DNA methyltransferase (DNMT), a DNA demethylase, a histone methyltransferase, a histone demethylase, or a portion thereof, or a zinc finger protein-based transcription factor or a portion thereof, or a combination thereof, and wherein the at least one DNA binding protein is a Cas9, dCas9, Cpf1, a zinc finger nuclease (ZNF), a transcription activator-like effector nuclease (TALEN), a homing endonuclease, a dCas9-FokI nuclease or a MegaTal nuclease.
Regarding claim 25, 26, 31, 36, and 43, Gersbach teaches a composition comprising a nucleic acid encoding a fusion molecule (“nucleic acid sequence encoding the fusion molecule” of claim 25) comprising dCas9 (“at least one DNA binding protein” and “dCas9” of claim 25 and “dCas9” of claim 36) and the KRAB domain (“at least one modulator of gene expression” and “a portion thereof” of “a zinc finger protein-based transcription factor” of claim 25 and 31) and a nucleic acid encoding guide RNA (SEQ ID NO: 42) complementary to the transcriptional start site of the mouse PCSK9 gene (“targeted to a genomic region near a PCSK9 gene and/or within a PCSK9 regulatory element” of claim 25; “transcription start site” of claim 26; “sgRNA” of claim 43) that reduced circulating PCSK9 and total cholesterol levels in serum after administration to mice (“provides a modification of at least one nucleotide near the PCSK9 gene and/or within a PCSK9 regulatory element” of claim 25) (page 118; page 119, para. 1 – 2; page 122; page 123, para. 1; Figure 11A).
Therefore, Gersbach anticipates claims 25, 26, 28, 31, 36, and 43.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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/Z.M.B./Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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