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 .
Election/Restrictions
Applicant’s election, without traverse, of Group I (claims 1-13 and 19-20) drawn to a method comprising ex vivo modification of any of the genes listed in Tables 1-7 or Figures 1-4 within at least one lymphoid or myeloid cell, in the response filed 05/22/2026 has been received and entered. Applicants further made a species election of IL1R1 as the gene selected from Tables 1-7 or Figures 1-4. Claims 1-13 and 19-20 read on the elected species and have been examined on the merits. Claims 14-18 are withdrawn as they are drawn to a non-elected invention.
Priority
Acknowledgement is made that the instant application is a National Stage of International application No. PCT/US2022/012988 (filed 01/19/2022), which claims the benefits of US Provisional Application No. 63/138,841 (filed 01/19/2021).
Claim Objections
Claims 1-3 and 5-8 are objected to because of the following informalities:
Claims 1-3 and 5-8 are objected to for improper format. Claims 1-3 and 5-8 reference Tables 1-7 and Figures 1-4 in the specification. MPEP 2173.05(s) states “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608 (bd. Pat. App. & Inter. 1993) (citation omitted).” The information from Tables 1-7 and Figures 1-4 pertinent to the claims does not qualify as an exception to circumstance. Therefore, the list of genes found in Tables 1-7 and Figures 1-4 must be incorporated into the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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, 9-13, and 19-20 are rejected under 35 USC 112, first paragraph, as failing to comply with the written description requirement. The claim 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(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 is directed to a method comprising ex vivo modification of a gene. The issue at present is the scope of “a method comprising ex vivo modification of a gene” covered by the claim. In giving the term “a method comprising ex vivo modification of a gene” its broadest reasonable interpretation, can include any method which alter a gene in any way (e.g. silencing of a gene by siRNA or shRNA, methods of editing a gene with an endonuclease, site directed mutagenesis, methods of adding reporter sequences to a gene, addition of sequences that affect stability of the nucleic acid or protein, methods comprising restriction enzymes and cloning, methods that introduce epigenetic modifications, etc.). Thus, a method comprising ex vivo modification of a gene is a genus of methods for altering a gene. Additionally, dependent claims 9-13 and 19-20 do not sufficiently limit the scope of “a method comprising ex vivo modification of a gene” to define a gene altering method and thus inherit the deficiencies of claim 1.
To satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed genus of gene altering methods, it must be clear that: (1) the identifying characteristic of the claims methods have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with known or disclosed correlation between function and structure, by a combination of such identifying characteristics; or (2) a representative number of species within the genus must be disclosed. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
While Applicants’ claims cover the full genus of a gene altering methods, Applicants’ disclosure of such methods is limited to inhibitory nucleic acids (e.g. siRNA, shRNA, RNAi), CRISPR-Cas9 mediated methods, and antibodies. Disclosure of three methods does not constitute a representative number for such a broad genus as is encompassed by the breadth of “methods comprising modification of a gene”. Therefore, Applicants have not disclosed a representative number of species, as would be required to support description and to show possession of the entire genus.
Regarding disclosure of structural and functional characteristics, no structural or chemical properties are disclosed which must be maintained in the claimed method or in the resulting modified gene. Therefore, Applicants have not disclosed the identifying characteristics of the claimed method. Furthermore, claims 9-13 and 19-20 are not limited to a resulting modification or method of modifying the gene, but rather cover any method.
Thus, one of ordinary skill in the art, in looking to the instant specification, would not be able to determine that Applicants were in possession of the invention, as claimed, at the time the invention was made. Accordingly, claim 1 and dependent claims 9-13 and 19-20 are considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 112(b)
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 1-13 and 19-20 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.
Claims 1-3 and 5-8 reference Figures 1-4 in the specification. MPEP 2173.05(s) states “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608 (bd. Pat. App. & Inter. 1993) (citation omitted).” The information from Tables 1-4 pertinent to the claims does not qualify as an exception to circumstance. The [information from the Figures, e.g. names of genes] can be incorporated into the claims. Furthermore, the genes in Figures 1-4 are not presented in a manner that is legible. Claims 1-3 and 5-8 are thus rejected as failing to particularly point out an distinctly claim the subject matter in a manner consistent with 35 USC 112(b). Additionally, claims 4, 9-13, and 19-20 depend from claim 1 without further defining the list of genes and thus inherit the deficiencies of claim 1.
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.
Claims 1-3, 7-9, 12, 13, 19, and 20 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Guilak et al (US20180201951 A1).
Guilak et al disclose a method of generating a modified cell comprising a modified endogenous gene (See claim 23 and ¶0007). The method comprising replacing an endogenous gene or fragment thereof with a transgene using a CRISPR/Cas9 system to generate the modified endogenous gene (See claim 23 and ¶0004). The transgene comprises a coding region operably linked to the promoter of the endogenous gene (See¶0099). Guilak et al further discloses a method of generating a modified cell comprising a modified endogenous gene comprising a signal peptide wherein the method comprise deleting or knocking out the signal peptide using a CRISPR/Cas9 system to generate the modified endogenous gene (See ¶0008). In one embodiment the endogenous gene is IL1R1 and exon 2 is the deleted peptide (See ¶0013 and ¶0097-0098 and Fig. 5). Deletion of exon 2 results in loss of IL1R1 expression in populations derived of modified cells (See Fig. 5C and ¶0013). The IL1R1 deleted cells were culture expanded (See ¶0200). The modified cell of Guilak et al can comprise a T-cell (See ¶00295 and claim 21). The modified cell of Guilak et al can be modified ex vivo (See ¶0072). Guilak et al further discloses a composition for treating a subject having a disease or disorder, the composition comprising a modified cell comprising a modified endogenous gene (See ¶0005 and claims 1 and 13). The composition can be administered to a subject in a therapeutically effective amount to prevent, treat or ameliorate a disease (See ¶0005 and claim 22). Diseases which can be treated by administering the composition comprising a modified cell comprise genetic, degenerative, or autoimmune diseases and cancer such as leukemias and lymphomas (See ¶0123 and ¶0128).
Regarding claim 1: Guilak et al discloses a method of generating a modified cell comprising a modified endogenous gene. The modified cell can be modified ex vivo and can comprise a T-cell which reads on a modified lymphoid cell. Guilak et al discloses an embodiment in which the modified gene is IL1R1. Thus, Guilak et al discloses a method comprising ex vivo modification of IL1R1 in a T-cell (reads on lymphoid cell) to generate at least one modified lymphoid cell.
Regarding claim 2: Following the discussion of claim 1 above, Guilak discloses deleting a signal peptide in an endogenous gene which reads on the modification is one or more deletion and further discloses replacing an endogenous gene or fragment thereof with a transgene which reads on the modification is one or more substitution or insertion.
Regarding claim 3: Following the discussion of claim 1 above, Guilak et al discloses deleting exon 2 of IL1R1 which results in loss of IL1R1 expression which reads on a reduction of expression.
Regarding claim 7: Following the discussion of claim 1 above, Guilak et al discloses knocking out exon 2 of IL1R1 using a CRISPR/Cas9 system which reads on a CRISPR mediated modification.
Regarding claim 8: Following the discussion of claim 1 above, Guilak et al discloses modifying an endogenous gene by replacing the gene or a fragment of the gene with a transgene operably linked to an endogenous promoter (reads on an expression cassette comprising a promoter operably linked to a nucleic acid segment comprising a coding region of a gene).
Regarding claims 9, 12, 13, 19: Following the discussion of claim 1 above, Guilak et al further discloses administering a composition comprising the modified cell to a subject to treat a disease in the subject which reads on the subject has a disease. The disease being treated in the subject can comprise an autoimmune disease (reads on an immune condition) or cancer.
Regarding claim 20: Following the discussion of claim 13 above, Guilak discloses the modified cells can be administered to a subject to treat cancers such as leukemia and lymphoma.
Claims 1, 3, and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sha et al (Frontiers in Immunology, 2016).
Sha et al discloses in vitro siRNA mediated silencing of IL-1R1 in naïve CD4+ T cells (See Secs. Abstract and Methods: siRNA Experiment). Use of siRNA resulted in decreased IL-1R1 expression (See Fig. 3).
Regarding claim 1: Sha et al discloses silencing IL-1R1 in naive CD4+ T-cells in vitro which reads on a method comprising ex vivo modification of IL1R1 within at least one lymphoid cell to generate at least one modified lymphoid cell.
Regarding claims 3 and 4: Following the discussion of claim 1 above, Sha et al discloses using siRNA (reads on an inhibitory nucleic acid) to silence IL-1R1. Sha et al further discloses decreased expression of IL-1R1 in cells transfected with IL-1R1 siRNA.
Claims 1, 3, 5-7 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bowles et al (WO2020081922 A1).
Bowles et al discloses a method of modulating expression of one or more genes in a cell using a compositions a vector comprising nucleotide sequences encoding one or more CRISPR-Cas system guide RNAs (gRNAs) and a RNA-directed nuclease (See abstract). The cell can be an invading immune cell including macrophages, T-cells, and neutrophils (See pg. 28, last paragraph – pg. 29, first paragraph). The gRNAs can target IL1R1 (See Table 3). The gRNA sequences can be sequences from the promoter region of the gene (See pg. 34 first paragraph). In an exemplary embodiment IL1R1 was significantly downregulated using 2 gRNAs (See pg. 6, second paragraph and Fig. 7C). Alternatively, Bowles discloses methods of increasing expression of one or more gene in cells comprising introducing a gRNA and a dCas9 (See pg. 3 last paragraph and claims 7 and 20). The method of Bowles et al is exemplified in vitro (See Example 2 pgs. 56-64)
Regarding claim 1: Bowles et al discloses a method of modulating expression of a gene in a cell. The gene can comprise IL1R1 and the cell can comprise an invading immune cell such as a macrophage, T-cell, and neutrophil (reads on a lymphoid cell or myeloid cell). Thus, Bowles et al discloses a method comprising modification of IL1R1 in a lymphoid or myeloid cell to generate at least one modified lymphoid or myeloid cell.
Regarding claim 3: Following the discussion of claim 1 above, Bowles et al discloses an exemplary embodiment in which expression of IL1R1 was downregulated using 2 gRNAs.
Regarding claim 5: Following the discussion of claim 1 above, Bowles et al discloses a method of increasing expression of one or more genes in a cell using a gRNA and a dCas9.
Regarding claims 6 and 7: Following the discussion of claims 1 and 5 above, Bowles et al discloses a method of modifying IL1R1 in a macrophage, T-cell, or neutrophil. The method for modifying a gene can comprise increasing expression of the gene using a CRISPR-Cas system gRNA and a dCas9 (reads on a CRISPR mediated modification). The gRNAs target the promoter region. Thus, a method for increasing expression of IL1R1 comprising gRNAs targeting the promoter region of IL1R1 and a dCas9 reads on the increased expression is by modification of one or more protomers.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-3, 7-13, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Guilak et al (US20180201951 A1).
The teachings of Guilak et al are set forth above.
Guilak anticipates claims 1-3, 7-9, 12, 13, 19, and 20.
Regarding claims 10 and 11: Following the discussion of claim 1 above, Guilak et al discloses quantifying IL1R1 expression in population of IL1R1 modified cells and culture expanding IL1R1 deleted cells which reads on incubating the at least one modified cell to form a population of modified cells. Additionally, Guilak et al discloses administering a therapeutically effective amount of a composition comprising modified cells to treat a subject.
Guilak et al does not exemplify culture expanding IL1R1 deleted T-cells, however, a person of ordinary skill in the art would have been motivated to culture expand IL1R1 deleted T-cells in order to produce a therapeutically effective amount (i.e. a population) of cells to administer to a subject. There is a reasonable expectation of success because Guilak et al discloses the modified cells can be culture expanded.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/ Examiner, Art Unit 1633
/ALLISON M FOX/ Primary Examiner, Art Unit 1633
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