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 .
Claims 1-10 are pending and under consideration.
Claim Objections
Claim 1 is missing essential elements of performing homology directed repair, i.e. Cas9, gRNA, and a homology repair template. The claim can be written more clearly as ---A method of improving the rat of homology directed repair (HDR), the method comprising:
administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant comprising the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian cell such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant---.
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.
Written Description
Claims 1-10 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.
A) The specification lacks written description for expressing any ubiquitin variant “corresponding to SEQ ID NO: 1” as required in claims 1 and 7 other than administering the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant comprising the amino acid sequence of SEQ ID NO: 1.
Claim 1 is drawn to a method of improving homology directed repair in a recipient cell, comprising: expressing a Ubiquitin polypeptide variant corresponding to SEQ ID NO:1 in the recipient cell, wherein an improvement of homology directed repair in the recipient cell is increased as compared to a cell that is not treated with the Ubiquitin polypeptide variant.
Claim 7 is drawn to a method of improving CRISPR-mediated gene editing in a target cell, comprising: transfecting a Ubiquitin polypeptide variant corresponding to SEQ ID NO: 1 or a Ubiquitin mRNA variant corresponding to SEQ ID NO: 31 into the target cell that harbors a CRISPR ribonucleoprotein complex
The concept of expressing a ubiquitin variant “corresponding to SEQ ID NO: 1” encompasses introducing the amino acid sequence of SEQ ID NO: 1 (claims 5 and 9) or the nucleotide sequence of SEQ ID NO: 31 which encodes SEQ ID NO: 1 (claims 6 and 10). It also encompasses introducing any functional or non-functional variant of SEQ ID NO: 1 or nucleic acids encoding them, e.g. introducing wild-type ubiquitin because the wild-type sequence “corresponds” to SEQ ID NO: 1. Claim 7 encompasses using any variant of SEQ ID NO: 31.
Glenn (WO 2024040059 published 2-22-24) taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant “corresponding to” the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (pg 5, Example 1).
Vakulskas (20230135471 effective filing date 3-18-22) taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1 (SEQ ID NO: 699) to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (para 107, 108, 123-130; claim 32).
De Ravin (Blood, 2021, Vol. 137, No. 19, pg 2598-2608) taught “Enhanced homology-directed repair for highly efficient gene editing in hematopoietic stem/progenitor cells” (title) and used i53, an “engineered ubiquitin variant with a high binding affinity to the TDD of 53BP1” (pg 2599, col. 1, 1st full paragraph).
The specification is limited to administering the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1. The specification does not correlate the amino acid sequence of SEQ ID NO: 1 to any functional or non-functional variant of (the variant of) SEQ ID NO: 1. The specification does not correlate the nucleic acid of SEQ ID NO: 31 to any functional or non-functional variant of (the variant of) SEQ ID NO: 31. Therefore, the concept of expressing a ubiquitin variant “corresponding to SEQ ID NO: 1” in claims 1 and 7 lacks written description other than administering the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1.
B) The specification lacks written description for “improving homology repair” in any “recipient cell” by expressing a ubiquitin variant as broadly required in claim 1. Claim 1 is recited above. The claim does not require administering any homology repair reagents to any cells. The claim encompasses performing the method in any cell in vitro or in vivo. The cell may be plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, bird, or mammalian. The claim encompasses administering a nucleic acid encoding the ubiquitin variant or (somehow) inducing expression of the ubiquitin variant in the absence of a nucleic acid encoding the ubiquitin variant. The teachings of Glenn (WO 2024040059 published 2-22-24) taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant “corresponding to” the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (pg 5, Example 1). The teachings of Glenn, Vakulskas, and De Ravin are discussed above. The specification is limited to administering the nucleic acid sequence of SEQ ID NO: 31 to isolated human T-cells and iPS cells, crRNA encoding Cas9 (Alt-R CRISPR-Cas9 – pg 4, last 5 lines), a sgRNA that targets a CD5, HPRT1, MET, SERPINC1, or HBB gene, and a homology repair template, i.e. donor” that complements each sgRNA (see pg 5-6, Tables 2-3). Claim 1 is missing the addition of crRNA encoding Cas9, a guide RNA, and a homology repair template, i.e. donor, to the cell. The specification does not correlate administering the nucleic acid sequence encoding the ubiquitin variant to administering the protein or to inducing expression of the ubiquitin variant in the absence of SEQ ID NO: 31. The specification does not correlate performing the method in mammalian cells to any plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, or bird cells. The specification does not correlate performing the method in isolated cells to cells in vivo. Accordingly, the concept lacks written description other than administering crRNA encoding Cas9, gRNA, a homology repair template, and the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant to an isolated mammalian cell such that homology directed repair occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence of SEQ ID NO: 31.
C) The specification lacks written description for “improving CRISPR-mediated gene editing” in any “recipient cell” by expressing a ubiquitin variant as broadly required in claim 7. Claim 7 is recited above. The claim does not require administering any “CRISPR-mediated gene editing” reagents to any cells. The claim encompasses performing the method in any cell in vitro or in vivo. The cell may be plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, bird, or mammalian. The claim encompasses administering a nucleic acid encoding the ubiquitin variant or (somehow) inducing expression of the ubiquitin variant in the absence of a nucleic acid encoding the ubiquitin variant. The teachings of Glenn, Vakulskas, and De Ravin are discussed above. The specification is limited to administering the nucleic acid sequence of SEQ ID NO: 31 to isolated human T-cells and iPS cells, crRNA encoding Cas9 (Alt-R CRISPR-Cas9 – pg 4, last 5 lines), a sgRNA that targets a CD5, HPRT1, MET, SERPINC1, or HBB gene, and a homology repair template, i.e. donor” that complements each sgRNA (see pg 5-6, Tables 2-3). Claim 7 is missing the addition of crRNA encoding Cas9, a guide RNA, and a homology repair template, i.e. donor, to the cell. The specification does not correlate administering the nucleic acid sequence encoding the ubiquitin variant to administering the protein or to inducing expression of the ubiquitin variant in the absence of SEQ ID NO: 31. The specification does not correlate performing the method in mammalian cells to any plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, or bird cells. The specification does not correlate performing the method in isolated cells to cells in vivo. Accordingly, the concept lacks written description other than administering crRNA encoding Cas9, gRNA, a homology repair template, and the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant to an isolated mammalian cell such that homology directed repair occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence of SEQ ID NO: 31.
Enablement
Claims 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for administering crRNA encoding Cas9, gRNA, a homology repair template, and the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian cell such that homology directed repair occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence of SEQ ID NO: 1
does not reasonably provide enablement for expressing a ubiquitin variant corresponding to SEQ ID NO: 1 by any means other than administering the nucleic acid sequence of SEQ ID NO: 31 or performing the method of claim 1 as broadly written. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
A) The specification does not enable expressing any ubiquitin variant “corresponding to SEQ ID NO: 1” as required in claims 1 and 7 other than administering the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant comprising the amino acid sequence of SEQ ID NO: 1.
Claims 1 and 7 are recited above.
The concept of expressing a ubiquitin variant “corresponding to SEQ ID NO: 1” encompasses introducing the amino acid sequence of SEQ ID NO: 1 (claims 5 and 9) or the nucleotide sequence of SEQ ID NO: 31 which encodes SEQ ID NO: 1 (claims 6 and 10). It also encompasses introducing any functional or non-functional variant of SEQ ID NO: 1 or nucleic acids encoding them, e.g. introducing wild-type ubiquitin because the wild-type sequence “corresponds” to SEQ ID NO: 1. Claim 7 encompasses using any variant of SEQ ID NO: 31.
The teachings of Glenn, Vakulskas, and De Ravin are discussed above.
The specification is limited to administering the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1. The specification does not correlate the amino acid sequence of SEQ ID NO: 1 to any functional or non-functional variant of (the variant of) SEQ ID NO: 1. The specification does not correlate the nucleic acid of SEQ ID NO: 31 to any functional or non-functional variant of (the variant of) SEQ ID NO: 31. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to express a ubiquitin variant “corresponding to SEQ ID NO: 1” as required in claims 1 and 7 other than administering the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1.
B) The specification does not enable “improving homology repair” in any “recipient cell” by expressing a ubiquitin variant as broadly required in claim 1. Claim 1 is recited above. The claim does not require administering any homology repair reagents to any cells. The claim encompasses performing the method in any cell in vitro or in vivo. The cell may be plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, bird, or mammalian. The claim encompasses administering a nucleic acid encoding the ubiquitin variant or (somehow) inducing expression of the ubiquitin variant in the absence of a nucleic acid encoding the ubiquitin variant. The teachings of Glenn, Vakulskas, and De Ravin are discussed above. The specification is limited to administering the nucleic acid sequence of SEQ ID NO: 31 to isolated human T-cells and iPS cells, crRNA encoding Cas9 (Alt-R CRISPR-Cas9 – pg 4, last 5 lines), a sgRNA that targets a CD5, HPRT1, MET, SERPINC1, or HBB gene, and a homology repair template, i.e. donor” that complements each sgRNA (see pg 5-6, Tables 2-3). Claim 1 is missing the addition of crRNA encoding Cas9, a guide RNA, and a homology repair template, i.e. donor, to the cell. The specification does not correlate administering the nucleic acid sequence encoding the ubiquitin variant to administering the protein or to inducing expression of the ubiquitin variant in the absence of SEQ ID NO: 31. The specification does not correlate performing the method in mammalian cells to any plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, or bird cells. The specification does not correlate performing the method in isolated cells to cells in vivo. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to perform the method of claim 1 other than administering crRNA encoding Cas9, gRNA, a homology repair template, and the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant to an isolated mammalian cell such that homology directed repair occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence of SEQ ID NO: 31.
C) The specification does not enable “improving CRISPR-mediated gene editing” in any “recipient cell” by expressing a ubiquitin variant as broadly required in claim 7. Claim 7 is recited above. The claim does not require administering any “CRISPR-mediated gene editing” reagents to any cells. The claim encompasses performing the method in any cell in vitro or in vivo. The cell may be plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, bird, or mammalian. The claim encompasses administering a nucleic acid encoding the ubiquitin variant or (somehow) inducing expression of the ubiquitin variant in the absence of a nucleic acid encoding the ubiquitin variant. The teachings of Glenn, Vakulskas, and De Ravin are discussed above. The specification is limited to administering the nucleic acid sequence of SEQ ID NO: 31 to isolated human T-cells and iPS cells, crRNA encoding Cas9 (Alt-R CRISPR-Cas9 – pg 4, last 5 lines), a sgRNA that targets a CD5, HPRT1, MET, SERPINC1, or HBB gene, and a homology repair template, i.e. donor” that complements each sgRNA (see pg 5-6, Tables 2-3). Claim 7 is missing the addition of crRNA encoding Cas9, a guide RNA, and a homology repair template, i.e. donor, to the cell. The specification does not correlate administering the nucleic acid sequence encoding the ubiquitin variant to administering the protein or to inducing expression of the ubiquitin variant in the absence of SEQ ID NO: 31. The specification does not correlate performing the method in mammalian cells to any plant, yeast, bacteria, insect, invertebrate, fish, amphibian, reptile, or bird cells. The specification does not correlate performing the method in isolated cells to cells in vivo. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to perform the method of claim 7 other than administering crRNA encoding Cas9, gRNA, a homology repair template, and the nucleic acid sequence of SEQ ID NO: 31 encoding a ubiquitin variant to an isolated mammalian cell such that homology directed repair occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence of SEQ ID NO: 31.
Indefiniteness
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 1-10 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 is indefinite because it is missing essential elements of performing homology directed repair, i.e. administering Cas9, gRNA, and a homology repair template to isolated cells such that homology directed repair (HDR) occurs.
Claim 1 is indefinite because it does not clearly set forth that a genetic modification or HDR event occurs in the cell.
Claim 1 is indefinite because the concept of an “improvement” being “increased” as compared to a control does not make sense. The rate of HDR events in a population of cells may increase or be improved as compared to a control. But the rate of HDR is not an “improvement” that is “increased” as claimed. The “improvement” doesn’t increase; the rate of HDR does.
Claim 5 is indefinite because SEQ ID NO: 1 protein and “transfecting” is limited to introducing nucleic acids into cells. Proteins are not “transfected” with proteins (see Wikipedia definition of “transfection”, 2025).
The term “suitable” in the phrase “suitable guide RNA” in claim 8 makes the claim indefinite. It is unclear whether the term “suitable” further limits the breadth of guide RNA or if the phrase encompasses any guide RNA. If the term “suitable” DOES further limit the phrase “guide RNA”, then it is unclear how, i.e. it is unclear when gRNA is “suitable”, i.e. the structures associated with “suitable” vs “unsuitable” gRNA. The claim already requires improved gene editing, which infers the gRNA must be functional, so it is unclear how the term “suitable” further limits the gRNA beyond being functional. If the term “suitable” is redundant, then delete it.
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) Claims 1-3, 5-10 are rejected under 35 U.S.C. 102a1 as being anticipated by Glenn (WO 2024040059 published 2-22-24).
Glenn taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant “corresponding to” the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (pg 5, Example 1). The ubiquitin variant used by Glenn “corresponds to” the protein of SEQ ID NO: 1 because it is similar and is derived from wild-type ubiquitin. This is equivalent to claims 1 and 7.
HEK293 or K562 cells are immortalized as required in claim 2.
Glenn taught HEK293 as required in claims 3.
Claim 5 has been included because proteins are not transfected into cells (see 112/2nd) and because Glenn introduced a nucleic acid sequence encoding a ubiquitin variant that “corresponded” to SEQ ID NO: 1.
Claim 6 has been included because Glenn introduced a nucleic acid sequence encoding a ubiquitin variant that “corresponded” to SEQ ID NO: 1.
Glenn used Cas9 and gRNA as required in claim 8 (Example 1).
Claim 9 has been included because proteins are not transfected into cells (see 112/2nd) and because Glenn introduced a nucleic acid sequence encoding a ubiquitin variant that “corresponded” to SEQ ID NO: 1.
Claim 10 has been included because Glenn introduced a nucleic acid sequence encoding a ubiquitin variant that “corresponded” to SEQ ID NO: 1.
B) Claims 1-3, 5-10 are rejected under 35 U.S.C. 102a1 as being anticipated by Vakulskas (20230135471 effective filing date 3-18-22).
Vakulskas taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1 (SEQ ID NO: 699) to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (para 107, 108, 123-130; claim 32). This is equivalent to claims 1 and 7.
HEK293 cells (para 34, 42, 48, 50, 54, 108, 117) are immortalized as required in claim 2.
Vakulskas taught HEK293 cells (para 34, 42, 48, 50, 54, 108, 117) as required in claims 3.
Claim 5 has been included because proteins are not transfected into cells (see 112/2nd) and because Vakulskas introduced a nucleic acid sequence encoding a ubiquitin variant that encodes SEQ ID NO: 1.
Claim 6 has been included because Vakulskas introduced a nucleic acid sequence encoding a ubiquitin variant that encodes SEQ ID NO: 1.
Vakulskas used Cas9 and gRNA as required in claim 8 (para 108, 117).
Claim 9 has been included because proteins are not transfected into cells (see 112/2nd) and because Vakulskas introduced a nucleic acid sequence encoding a ubiquitin variant that encodes SEQ ID NO: 1.
Claim 10 has been included because Vakulskas introduced a nucleic acid sequence encoding a ubiquitin variant that encodes SEQ ID NO: 1.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A) Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Glenn (WO 2024040059 published 2-22-24) in view of Li (Nucleic acids research, 2018, Vol. 46, No. 19, pg 10195-10215).
Glenn taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant “corresponding to” the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (pg 5, Example 1). The ubiquitin variant used by Glenn “corresponds to” the protein of SEQ ID NO: 1 because it is similar and is derived from wild-type ubiquitin. This is equivalent to claims 1 and 7.
Glenn did not teach transfecting induced pluripotent stem cells as required in claim 4.
However, Li taught using a CRISPR system to edit genes in human iPS cells (title; Materials and Methods).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to perform the method of Glenn using iPS cells described by Li. Those of ordinary skill in the art at the time of filing would have been motivated to swap the cells of Glenn with the iPS cells of Li to obtain multipotent cells with an edited gene.
Claims 2, 3, 5-10 have been included for reasons set forth above.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
.
B) Claims 1-3, 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over Glenn (WO 2024040059 published 2-22-24) in view of Vakulskas (20230135471)
Glenn taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant “corresponding to” the amino acid sequence of SEQ ID NO: 1 to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (pg 5, Example 1). The ubiquitin variant used by Glenn “corresponds to” the protein of SEQ ID NO: 1 because it is similar and is derived from wild-type ubiquitin. This is equivalent to claims 1 and 7.
Glenn did not teach transfecting the cells with a nucleic acid sequence encoding a ubiquitin variant having the amino acid sequence of SEQ ID NO: 1.
However, Vakulskas taught transfecting the cells with nucleic acid sequence SEQ ID NO: 699 encoding a ubiquitin variant with an affinity for 53BP1 having the amino acid sequence of SEQ ID NO: 1 (title; Example 1; SEQ ID NO: 699).
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Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to perform the method of Glenn using the ubiquitin variant described by Vakulskas. Those of ordinary skill in the art at the time of filing would have been motivated to swap the cells of Glenn with the iPS cells of Li to obtain multipotent cells with an edited gene.
Claims 2, 3, 5-10 have been included for reasons set forth above.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
C) Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Vakulskas (20230135471 effective filing date 3-18-22) in view of Li (Nucleic acids research, 2018, Vol. 46, No. 19, pg 10195-10215).
Vakulskas taught administering crRNA encoding Cas9, gRNA, a homology repair template, and a nucleic acid sequence encoding a ubiquitin variant that has the amino acid sequence of SEQ ID NO: 1 (SEQ ID NO: 699) to an isolated mammalian HEK293 or K562 cells such that HDR occurs at a rate greater than administering crRNA encoding Cas9, gRNA, and a homology repair template in the absence of the nucleic acid sequence encoding the ubiquitin variant (para 107, 108, 123-130; claim 32). This is equivalent to claims 1 and 7.
Vakulskas did not teach transfecting induced pluripotent stem cells as required in claim 4.
However, Li taught using a CRISPR system to edit genes in human iPS cells (title; Materials and Methods).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to perform the method of Vakulskas using iPS cells described by Li. Those of ordinary skill in the art at the time of filing would have been motivated to swap the cells of Glenn with the iPS cells of Li to obtain multipotent cells with an edited gene.
Claims 2, 3, 5-10 have been included for reasons set forth above.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
De Ravin (“Enhanced homology-directed repair for highly efficient gene editing in hematopoietic stem/progenitor cells”, Blood, 2021, Vol. 137, No. 19, pg 2598-2608) who used i53, an “engineered ubiquitin variant with a high binding affinity to the TDD of 53BP1” (pg 2599, col. 1, 1st full paragraph).
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights