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 .
Status Summary
Claims 1- 42 are pending.
Claims 1- 42 are considered on the merits.
Claims 30 and 34 are objected.
Claims 4, 12, 20- 22, 24- 28, 30-34, 38, and 40- 42 are rejected.
Claims 1- 3, 5- 11, 13- 19, 23, 29, 35- 37, and 39 are allowed.
Claim Objections
Claim 30 is objected to because of the following informalities: Claim 30, 3rd line of (iii) recites ”prior to the delivering the Cas polypeptide/guide polynucleotide complex.” There appears to be an extra word “the.” This examiner interprets this clause as ”prior to delivering the Cas polypeptide/guide polynucleotide complex.”
Claim 34 is objected to because of the following informalities: Claim 34, preamble recites ”The method of Claims 33.” The word “claims” should be singular. This examiner interprets this clause as ”The method of Claim 33.”
Appropriate correction is required.
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 12, 31, 38, 41, 42 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.
Those claims included in the statement of rejection but not otherwise discussed are rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Regarding claim 12, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 12 recites the broad recitation “N,” and the claim also recites “(T>W>C)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Dependent claims 41 and 42 fail to remedy the indefiniteness.
Claim 38 recites the limitation "the cell" in the final two words of line 3. There is insufficient antecedent basis for this limitation in the claim. Claims 1, 7, 29, and 36 from which claim 38 depends, fail to introduce “a cell.”
Claims 41 and 42 recites the limitation "The inactivated engineered Cas polypeptide" in the first line of the preamble. There is insufficient antecedent basis for this limitation in the claim. Claims 1 and 12 from which claims 41 and 42 depend, recite “an engineered Cas polypeptide” but fail to introduce “an inactivated engineered Cas polypeptide.”
Claim Rejections - 35 USC § 112
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.
Claims 20- 22 are 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.
Claim 1 requires a “Cas polypeptide.” Claim 20 recites “A polynucleotide encoding the engineered Cas polypeptide of claim 1.” However, the invention “polynucleotide encoding a polypeptide” may be practiced without necessitating the use of a polypeptide. Therefore, claim 20 fails to include all of the limitations of claim 1 from which it depends.
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. Dependent claims 21 and 22 are similarly indefinite and fail to remedy the indefiniteness of claim 20.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 24- 28, 30- 34 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 24 recites “A eukaryotic cell comprising the engineered Cas polypeptide of Claim 1.” The specification states “In some embodiments, the cell is selected from the group consisting of: an archaeal cell… and a human cell. In some cases, … the cell is in vivo.” ([0251]). Similarly, claim 25 recites “wherein the eukaryotic cell is… an animal cell,” claim 30 recites “The method of Claim 29, wherein the target polynucleotide is a target genomic sequence of a cell,” claim 31 recites “wherein the cell is a eukaryotic cell,” claim 32 recites “wherein the eukaryotic cell is derived or obtained from an animal.” Accordingly, the broadest reasonable interpretation (BRI) of the term “A eukaryotic cell,” “an animal cell,” and “a cell” embraces a human cell and wherein the cell resides or is intended to reside in a human organism and therefore is otherwise inseparable from the human. In view of the BRI, a human comprising the cell would be encompassed by the claimed product. Claims 25- 28 depend (directly or indirectly) on claims 24 or 25. Claims 31- 34 depend (directly or indirectly) on claims 30, 31, or 32.
Allowable Subject Matter
Claim 1- 3, 5- 11, 13- 19, 23, 29, 35- 37, and 39 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 1, Hou (Hou US 20200190494 A1, published 2020 June 18) is the closest prior art found by this examiner. Hou teaches “a CRISPR-Cas endonuclease comprising at least one zinc-finger-like domain, at least one bridge-helix-like domain, a [C-terminal] tri-split RuvC domain (comprising non-contiguous RuvC-I domain, RuvC-II domain, and RuvC-III domain),” [0009, Fig. 2 shown below].
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Hou further teaches “Fig. 8J depicts Cas-alpha 10 from Syntrophomonas palmitatica (SEQ ID NO:37) which features a unique motif of three zinc finger domains” [0030, Fig. 8J]; and “Cas endonucleases described herein are capable of creating a double-strand break in, or adjacent to, a target polynucleotide that comprises an appropriate PAM” [0021]. Furthermore, Hou’s SEQ ID No 37 is a Cas nuclease, 497 AA long, comprises a G226 when aligned to instant SEQ ID No 20, and Hou’s SEQ ID No 37 shares 100% identity with the instant claim’s 497 AA Cas nuclease SEQ ID No 20.
Therefore, Hou teaches the claim elements “An engineered Cas polypeptide, comprising: (a) a C-terminal tri-split RuvC domain and three zinc finger motifs; and (b) one or more of the following amino acids at positions relative to an alignment with SEQ ID NO:20: Glycine at 226, Glycine at 230, Glutamate at 327, Glutamate at 329, Cysteine at 376, Cysteine at 379, Cysteine at 395, Cysteine at 398, and Cysteine at 406; … and wherein the engineered Cas polypeptide is capable of site specifically binding a target site of a polynucleotide.”
Furthermore, whereas the Cas protein claimed is not the Cas protein of SEQ ID No 20 of the instant application, it notable that WT Cas endodeoxyribonuclease Cas12f1 of Syntrophomonas palmitatica (503 AA, NCBI Reference Sequence: WP_054696859.1) comprises 98.81% identity with SEQ ID No 20 (497 AA) where the only difference is Cas12f1 has six additional residues at 407-412.
Regarding the claim limitation “a C-terminal tri-split RuvC domain and three zinc finger motifs,” it is worth noting that Koonin (Koonin et al. Curr Opin Microbiol. 2017 Jun;37:67-78.) teaches TnpB protein with a tri-split RuvC domain and a single zinc finger (Figure 3).
However, this examiner has been unable to find prior art that teaches the claim limitation “wherein the engineered Cas polypeptide does not comprise at least one of the following: Phenylalanine at relative position 38, Alanine at relative position 40, Histidine at relative position 79, Glutamate at relative position 81, Alanine at relative position 87, Threonine at relative position 335, Cysteine at relative position 409, Glutamate at relative position 421, Lysine at relative position 467, or Glutamate at relative position 468.”
The claim’s combination of 1) protein domain architecture, 2) sequence restricted to alignment with SEQ ID No 20, and 3) the exclusion of specific residues’ separate the invention from the prior art.
Claim 2- 3, 5- 11, 13- 19, 23, 29, 35- 37, and 39 are directly or indirectly dependent on claim 1 and are therefore allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON DUREL WARD whose telephone number is (571)272-8495. The examiner can normally be reached Monday to Thursday 8:00AM 6:00PM.
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/AARON DUREL WARD/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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