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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/26/2026 has been entered.
Receipt is acknowledged of amendment, filed 03/26/2026, wherein claims 1-4, 10-18, 20-23, 27 and 28 are cancelled, claim 9 is currently amended and claims 5-8, 19 and 24-26 were previously presented. Claims 5-9, 19 and 24-26 are currently pending.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Applicant's claim for priority based on the foreign applications filed as EP 20157371.4 on 02/14/2020, EP 19191840.8 on 08/14/2019 and EP 19162150.7 on 03/12/2019.
All claims are given the priority date of 03/12/2019.
Claim Objections
The previous objection of claim 16 has been withdrawn in view of Applicant’s cancellation of the claim filed on 03/26/2026.
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 5-9,19 and 24-26 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 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.
Claim 5 is drawn to a genus of a Streptococcus pyogenes Cas9 protein. The rejected claims thus comprise a genus of Streptococcus pyogenes Cas9 protein that encompass a sequence of SEQ ID NO: 1 wherein the arginine at position 63 and the glutamine at position 768 are each replaced by alanine. The phrase “an amino acid sequence according to SEQ ID NO: 1” is interpreted as any two or more consecutive amino acids in SEQ ID NO: 1.
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 a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification teaches the (wild type (wt)) SpCas9 protein has the sequence as shown in SEQ ID NO: 1 (Page 19, Paragraph 2). The specification continues to teach that the SpCas9 sequence has substitutions at positions 68 and 768 for alanine of the sequence of SEQ ID NO: 1 that results in enhanced specificity compared to the wild-type sequence shown as SEQ ID NO: 1 (Page 20, Paragraphs 5-6 bridging Page 21, Paragraph 1). No description is provided of any variant or fragment of SEQ ID NO: 1 capable of successfully functioning as a SpCas9 protein for the instant invention.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the SpCas9 protein comprising the full length of SEQ ID NO: 1 wherein positions 68 and 768 are substituted for an alanine amino acid and at least 90% identical over the entire length of SEQ ID NO: 1. The results are not necessarily predictive of any variant or fragment of SEQ ID NO: 1 capable of successfully functioning as a SpCas9 protein. Thus, it is impossible for one to extrapolate from the few examples described herein those variants or fragments of SEQ ID NO: 1 that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of fragments or variant of the wild-type SpCas9 sequence identified as SEQ ID NO: 1 that would provide the same success of specificity to target sites. Doudna et al (Science 346, Pages 1258096-1 to 1258096-10 (2014)) teaches that the elements of the SpCas9 protein are important for its level of DNA cleavage and reduction of targeting off-target sites (Page 1258096-4, Column 1 bridging Column 2 and Page 1258096-6, Column 3). Thus, it is understood that alteration of the SpCas9 sequence would alter the specificity and off-targeting effects of the protein as compared to the wild-type.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 5-9,19 and 24-26.
It would be remedial to amend the claims to recite “A polynucleotide encoding a Streptococcus pyogenes Cas9 (SpCas9) protein comprising or consisting of:
(i) a polypeptide with the [[an]] amino acid sequence according to SEQ ID NO: 1 wherein the arginine at position 63 and the glutamine at position 768 are each replaced by alanine; or
(ii) a polypeptide with an amino acid sequence having at least 90% sequence identity to the amino acid sequence according to SEQ ID NO: 1, wherein the residue corresponding to the arginine at position 63 of SEQ ID NO: 1 and the residue corresponding to the glutamine at position 768 of SEQ ID NO: 1 are each replaced by alanine, and wherein said polypeptide has enhanced specificity compared to a polypeptide with the amino acid sequence according to SEQ ID NO: 1.”
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 24 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Independent claim 5 recites the limitation within part (ii) that the amino acid sequence of the instantly claimed invention has to have enhanced specificity compared to a polypeptide with the amino acid sequence according to SEQ ID NO: 1. Claim 24 recites that the SpCas9 protein in item (i) has enhanced specificity compared to a polypeptide with the amino acid sequence according to SEQ ID NO: 1. However, the scope is not further limited in that if the sequence is SEQ ID NO: 1 with the specific mutations of positions 68 and 768 for alanine, it would match the limitations of both item (i) and (ii). As well as item (ii) already recites the limitation of enhanced specificity compared to a polypeptide with the amino acid sequence according to SEQ ID NO: 1. Therefore, the scope of claim 24 would be the same scope as claim 5 item (ii). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Amendments - Claim Rejections - 35 USC § 112
The previous rejection of claims 10-12, 14-16, 20-23, 27 and 28 under 35 U.S.C. 112(a), first paragraph, has been withdrawn in view of Applicants amendments to the claims filed on 03/26/2026.
Claim Rejections - 35 USC § 101
The previous rejection of claim 9 under 35 U.S.C. 101 has been withdrawn in view of Applicants amendments to the claims filed on 03/26/2026.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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