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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 63/232,432 on 08/12/2021.
All claims are given the priority date of 08/12/2021.
Application Status
Receipt is acknowledged of amendment, filed 09/13/2024. Claims 1, 3-8, 12, 18-19, 22, 28-30, 32, 34, 38, 42-43 and 48 are currently pending and under consideration.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statement filed on 09/13/2024 have been received and all references have been considered.
Claim Objections
Claims 4 and 19 comprises periods within the claims. MPEP 608.01(m) states, “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.” 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 1, 3-5, 7, 12, 18-19, 22, 28-30, 32, 34, 38, 42-43 and 48 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.
Claims 1, 3-5, 7, 12, 30, 34 and 38 are drawn to a genus of variant Cas12i3 polypeptide sequences. The rejected claims thus comprise a genus of Cas12i3 polypeptide sequences that encompass 22 single and/or combination mutations to the wildtype sequence that would still be capable of functioning as a Cas12i3 polypeptide.
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 provides 22 single amino acid mutations and any combinations of the single amino acid mutations of the wildtype Cas12i3 polypeptide sequence for use in a gene editing system (Page 30, Lines 23-26, Table 3 and Table 4). Figures 1 and 2 of the drawings filed on 02/09/2024 show several single and combination of mutations relative to the wildtype Cas12i3 polypeptide that resulted in low or no indel activity, specifically single mutations E596R, N597R, Y564R, Y545R, C594R, T1040R, L797G, Q660R, S663R and T667R as well as the combination mutations of S536R_S801R, S536R_K583R_S801R, S536R_K583R_ N711R_C724R_S801R, and S536R_K583R_N711R (Pages 1-2 of Drawings; Fig. 1 and 2). The specification provides a list of the single and combination mutations to the Cas12i3 wildtype sequence that would result in higher percent indels relative to the wildtype Cas12i3 (Page 73, Lines 8-12), specifically Table 6 found on Pages 73-74 of the specification provides the specific single mutations and combination of mutations that resulted in improved function relative to the wildtype Cas12i3. The specification describes the use of instant SEQ ID NO: 7 which provides the Cas12i3 polypeptide with the combination of mutations of K583R N711R C724R which provided the highest average percent indel activity of 2.51 (Page 32, Lines 10-15 and Page 74, Table 6). No description is provided of how the other single mutations or combination of mutations relative to the wildtype Cas12i3 polypeptide sequences would function.
While Figures 1 and 2 show that some specific amino acid substitutions relative to SEQ ID NO: 3 are capable of providing an enhanced percentage of indels in cells, the mechanism for the enhancement is not disclosed. The disclosure does not provide a structure-function correlation for each of the claimed functions of claim 30. Applicant is not in possession of variants for each of the claimed functions.
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 single or combination of mutations relative to the wildtype Cas12i3 polypeptide sequence (instant SEQ ID NO: 3) that resulted in an average indel percentage of at least 0.88 as shown in Table 6 on Pages 73-74 of the specification. The results are not necessarily predictive of any other single mutations or combination of mutations relative to the wildtype 12i3 polypeptide sequence capable of improved or increased percent indel activity. Thus, it is impossible for one to extrapolate from the few examples described herein those single or combination of mutations capable of increased indel activity relative to the wildtype Cas12i3 polypeptide sequence 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 any other single mutations or combination of mutations relative to the wildtype 12i3 polypeptide sequence capable of improved or increased percent indel activity.
Duan et al (Innovation (Camb). 2024 Jan 8;5(2):100564, pgs. 1-9) teaches various substitution mutations of the Cas12i3 and how the single mutations and/or combination of mutations effect the indel percentage of the mutated Cas12i3 polypeptide relative to the wildtype Cas12i3 (Page 1, Abstract). Duan teaches 26 single substitution mutations of the wildtype Cas12i3 polypeptide and their relative editing efficiency compared to the wildtype (Page 2, Fig 1C and D). Duan teaches different combinations of the single mutations relative to the wildtype Cas12i3 polypeptide sequence showed variations in editing efficiencies that require assay to determine (Page 1, Column 2 bridging Page 2, Column 1; and Page 3, Fig. 2D). Duan teaches the combination of 5 of the single substitution mutations, named as variant Cas-SF01, relative to the wildtype Cas12i3 that showed the highest gene editing efficiency among all of the Cas12i3 variants tested in their study (Page 2, Column 2 and Page 3, Fig. 2E).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1, 3-5, 7, 12, 18-19, 22, 28-30, 32, 34, 38, 42-43 and 48.
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 38, 42 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.
Claim 38 provides for the method of producing the variant Cas12i3 polypeptide of claim 1, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a method without any active, positive steps delimiting how this method is actually practiced.
Claim 42 provides for the method of delivering the variant Cas12i3 polypeptide of claim 1, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a method without any active, positive steps delimiting how this method is actually practiced.
Claim 43 provides for the use of delivering the variant Cas12i3 polypeptide of claim 1 within a delivery composition, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
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 12, 18, 19, 22, 28, 29 and 48 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 12 includes an embodiment where the amino acid sequence of claim 1 is substituted with a nucleic acid encoding the sequence of claim 1. 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.
Claim 32 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. Claim 32 is drawn to a composition comprising the polypeptide of claim 1 but does not add a further limitation. 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.
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.
Claims 38, 42 and 43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claims are not drawn to a machine, manufacture or composition of matter. Although, the claims do encompass a process, the process does not include steps but instead simply recites method claims without the steps of how that method would be accomplished. Specifically, claim 38 relies from claim 1 and recites “a method of producing the variant Cas12i3 polypeptide”; claim 42 relies from claim 1 and recites “a method of delivering the variant Cas12i3 polypeptide”; and claim 43 relies from claim 42 and recites “wherein the Cas12i3 polypeptide is present within a delivery composition”. Therefore, without the proper steps of how the Cas12i3 would be produced and then how the Cas12i3 would be created into a delivery composition and delivered to a cell and/or organism the method steps cannot be considered a process. Thus, the claims do not recite one of the four categories required for patent eligible subject matter (See MPEP § 2106.03).
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 34 is 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 34 recites “A cell comprising the variant Cas12i3 polypeptide of claim 1”. The specification provides that the cell is a human cell and that the cell is in vitro, in vivo or ex vivo and to be delivered to a subject (Page 5, Line 5, 25 and 35; Page 60, Lines 25-32 and Page 67, Line 11). Therefore, the specification envisions that the cell provided in claim 34 is a human cell present within a human being. Thus, the claim reads on a human cell comprising the composition of claim 1 present within a human being, which is non-statutory subject matter.
Allowable Subject Matter
Claims 6 and 8 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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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