DETAILED ACTION
This action is in reply to papers filed 12/6/2024. Claim 1-20 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20250332231A1, Published 10/30/2025.
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 1-3, 6-7, 9-11, 13-14, 17, 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.
Each of claims 2, 9, 11, and 17 refer to a “healthy cell”. The metes and bounds of this limitation, in the context of the claimed invention, is unclear. The specification does not disclose what is a “healthy cell”. And although the specification discloses some cells are considered to be " healthy”, i.e., cells that do not contain genomic instability (Pg. 1,para. 7), these are merely exemplary and non-limiting. Thus, it is unclear whether a healthy cell is a cell that maintains its integrity, a cell that does not proliferate in an uncontrolled manner, a cell that does not comprise accumulated mutations or some other unspecified characteristic. Accordingly, the metes and bounds of these claims are unclear. Note that the Courts have consistently held that “[I]f a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.” Ex parte Miyazaki, 89 U.S.P.Q.2d 1207, 1211 (B.P.A.I. 2008) (precedential); standard expressly approved in In re Packard, 110 U.S.P.Q.2d 1785, 1789 (Fed. Cir. 2014).
Each of claim 1-3, 6, 9-11 ,13, 17 and 20 are indefinite in their recitation of “a fusion sequence” because it is unclear what a fusion sequence refers to. A fusion of a DNA and amino acid sequence, a fusion of more than one DNA sequence, a fusion of a DNA sequence and an RNA sequence, a fusion of at least two polypeptides?. As such the metes and bounds of the claim are indefinite. For the sake of compact prosecution, the Examiner is interpreting a fusion sequence as a nucleic acid target sequence recognized by the CRISPR-Cas system including the protospacer adjacent motif (PAM) in the DNA immediately downstream of the target region.
Claims 2 and 11 are indefinite in its recitation of “designing the guide RNA” or “assembling the guide RNA”, respectively, by “identifying the fusion sequence based on a difference between the wild-type sequence and the mutated sequence” is unclear. That is, it is wholly unclear how the identification of the fusion sequence takes place after the assembling or designing of the guide RNA. Stated another way, the identification of the fusion sequence is first required to design or assemble the guide RNA. Therefore, how identifying the fusion sequence after the design or assemble of the gRNA is unclear. As such, the metes and bounds of the claims 2 and 11 are indefinite.
Claims 6-7, 13-14 and 19-20 are incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. While all of the technical details of a method need not to be recited, the claims should include enough information to clearly and accurately describe the invention and how it is to be practice. It is unclear how: (i) the Cas endonuclease induces cell death by incorporating a protein coding gene sequence that results in expression of a lethal protein or (ii) the Cas endonuclease induces expression of a marker cell surface protein by incorporating a protein coding gene. Generally, a Cas endonuclease is a specialized protein that acts as a molecular scissor to cut DNA at specific, targeted locations. A Cas endonuclease does not- in and of itself- incorporate a protein coding gene sequence that results in cell death or the expression of a marker protein. Therefore, it is wholly unclear how the Cas9 endonuclease of the claims induces cell death by incorporating a protein coding gene sequence or induces expression of a marker cell surface protein.
Claims 6 and 13 recite, inter alia, “wherein the Cas endonuclease induces cell death by generating…”. There is a lack of antecedent basis issue with this limitation as there is no previous recitation in independent claims 1 or 9 of a cell death. Note that, when taken in context, it is clear that limitation implies cell death has previously occurred.
Clarification on all of these matters is requested.
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.
Prior Art Rejection 1
Claim(s) 1, 3-5, 9-10 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Daly et al. (PgPub US20180362654A1, Filed 12/9/2016).
Daly et al. disclose certain cancer cells that become resistant to EGFR/ErbB3 blockade express constitutively active FGFR3-TACC3 fusion proteins as endogenous drivers of resistance to targeted therapy (’~fusion sequence that is in a cancer cell but not in a healthy cell of the subject’ as in claim 1 (in-part), as in claim 9 (in-part)) (Pg. 1, para. 7). To investigate whether the endogenous FGFR3-TACC3 fusion proteins expressed in the FaDu variants are responsible for the resistant phenotype, Daly employed CRISPR/Cas9 technology (as in claim 4 and claim 12) to inactivate the FGFR3-TACC3 fusion genes. Daly used lentivirus to deliver Cas9 nuclease and single guide RNAs (sgRNAs) (as in claim 5) and to FaDu V1 and V2 cells. Four sgRNAs targeting early exons in FGFR3 (exon 2 or exon3) were tested and two of the four sgRNAs almost completely eliminated expression of the FGFR3-TACC3 fusion proteins (and native FGFR3) in FaDu V1 and V2 cells (FIG. 9A) (as further in claim 1, claim 3, claim 9 and as in claim 10) (Pg. 16, para. 121). In one embodiment, Daly discloses the cancer is lung cancer (as in claim 16) (Pg. 11, para. 76). Daly discloses this method can be applied to a subject (Abstract).
Accordingly, Daly anticipates the claimed invention.
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.
Prior Art Rejection 2
Claim(s) 8 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Daly et al. (PgPub US20180362654A1, Filed 12/9/2016) as applied to claims 1, 3-5, and 9-10 and further in view of Capelletti et al. (Clin Cancer Res (2014) 20 (24): 6551–6558.).
The teachings of Daly et al. are relied upon as detailed above. However, Daly fails to teach the cancer cell comprises a genetic rearrangement (as in claim 8 and 15).
Before the effective filing date of the claimed invention, Capelletti teaches the identification of oncogenic alterations in subsets of patients with non–small cell lung cancer (NSCLC) has accelerated the development of targeted therapies including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors. Although oncogenic alterations are more prevalent in never smokers than smokers with NSCLC, not all cancers from never smokers contain a known alteration. By studying a cohort of lung adenocarcinomas from never smokers without a known oncogenic alteration, Capelletti identified recurrent FGFR3–TACC3 rearrangements (as in claim 8 and claim 15). This fusion gene is oncogenic in vitro and the transformed cells are sensitive to fibroblast growth factor receptor (FGFR) kinase inhibitors. Capelletti teaches these findings identify a population of patients with lung cancer who could benefit from treatment with FGFR kinase inhibitors (Pg. 6552, ‘Translation Relevance’).
When taken with the teachings of Daly et al., wherein Daily teaches using CRISPR/Cas9 complexes to treat a lung cancer having a FGFR3-TACC3 mutation in an endogenous gene, one of ordinary skill in the art would have found it prima facie obvious to target a NSCLC because Capelletti identified recurrent FGFR3–TACC3 rearrangements in NSCLC that would benefit from treatment with FGFR kinase inhibitors.
Thus, the combination would have been prima facie obvious.
Prior Art Rejection 3
Claim(s) 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Hahn et al. (PgPub 20170114413 Filed 10/16/2020) and Daly et al. (PgPub US20180362654A1, Filed 12/9/2016).
Regarding claim 17, Hahn et al. teach a method for preparing a sequence-specific DNA damaging agent suitable for the treatment of a lung cancer of a human subject, said method comprising identifying a cancer cell-specific copy number amplification of said epithelial cell cancer in genomic DNA of the human subject, wherein the cancer cell-specific copy number amplification comprises a non-coding, non-gene regulatory, intergenic region, and producing a sequence-specific DNA damaging agent, wherein said sequence-specific DNA damaging agent is a CRISPR-Cas system nuclease comprising a guide nucleic acid sequence that is a perfect match with a nucleic acid sequence of the non-coding, non-gene regulatory, intergenic region across a span of at least twenty nucleotides in length within said cancer cell-specific genomic DNA copy number amplification of the human subject and thereby targets the non-coding, non-gene regulatory, intergenic region within said cancer cell-specific genomic DNA copy number amplification of the human subject for damage, wherein the guide nucleic acid sequence is not a perfect match with any gene or gene expression regulatory sequence in the genome of the human subject (Pg. 4, para. 31, para. 33; Pg. 10, para. 125; Pg. 19, para. 206; Pg. 6, para. 80). Hahn teaches tumor cell death (as in claim 18) (Pg. 2, para. 16).
However, Hahn et al. fails to teach the gRNA hybridizes to fusion sequences of the genome that are in a cancer cell but not a healthy cell.
Before the effective filing date of the claimed invention, Daly et al. teach certain cancer cells that become resistant to EGFR/ErbB3 blockade express constitutively active FGFR3-TACC3 fusion proteins as endogenous drivers of resistance to targeted therapy (’~fusion sequence that is in a cancer cell but not in a healthy cell of the subject’ (as further in claim 17) (Pg. 1, para. 6).
When taken with the teachings of Hahn et al., wherein Hahn teaches using a method for preparing a DNA targeting agent suitable for the treatment of a cancer type, said method comprising identifying a cancer cell-specific sequence variation of said cancer type and producing a sequence-specific DNA targeting agent targeting said sequence, one of ordinary skill in the art would have found it prima facie obvious to target the FGFR3 gene in a subject having cancer for the purposes of treating the cancer. The skilled artisan would have been motivated to do so because Daly teaches such cancers are resistant to EGFR/ErbB3 blockade.
Thus, the combination would have been prima facie obvious.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632
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