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 .
DETAILED ACTION
Status of the Claims
Claims 1-22 are pending and the subject of this NON-FINAL Office Action. This is the first action on the merits.
Priority
The effective filing date of the claims is 09/07/2023, because the document filed on that date (this application) is the first priority document to disclose reverse transcriptase with both mutations M230I and Y501W.
Claim Rejections - 35 USC § 102
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) A person shall be entitled to a patent unless –
(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; or
(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 1-6 and 12-21 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by IVANCIC (US 20260125669, effective filing 10/7/2022).
As to claim 1, IVANCIC teaches a method of screening for one or more mutations in a nucleic acid sequence encoding a protein in a target cell; wherein the one or more mutations conveys a phenotypic property to the protein, comprising:
(a) transducing the target cell with at least one lentiviral particle comprising a pol gene nucleic acid sequence encoding a reverse transcriptase sequence comprising a M230I and a Y501W mutation with reference to SEQ ID NO: 1 (claims 16-34; paras. 0032 & 0091);
(b) contacting the target cell with a biomolecule after step (a), to select for the target cell with the phenotypic property in a target cell population (id.);
(c) obtaining the nucleic acid sequence from the target cell with the phenotypic property (id.); and
(d) screening for one or more mutations that convey the phenotypic property, wherein screening comprises comparing the nucleic acid sequence encoding the protein from the target cell with the phenotypic property, to a control nucleic acid sequence, wherein the control nucleic acid sequence encodes the protein without the one or more mutations (id.).
As to claim 2, IVANCIC teaches the reverse transcriptase sequence comprises an amino acid sequence as set forth in SEQ ID NO: 14, or a sequence at least about 80% identical thereto (paras. 0091-93).
As to claim 3, IVANCIC teaches the nucleic acid sequence encoding the protein is a genomic nucleic acid sequence (sequence of interest, or Sol; claim 16).
As to claim 4, IVANCIC teaches the nucleic acid sequence encoding the protein is a heterologous nucleic acid sequence (id.).
As to claim 5, IVANCIC teaches the at least one lentiviral particle further comprises the heterologous nucleic acid sequence (id.).
As to claim 6, IVANCIC teaches the lentiviral particle further comprises an inducible promoter operatively linked to the heterologous nucleic acid sequence (para. 0237).
As to claim 12, IVANCIC teaches the phenotypic property is target cell viability in presence of the biomolecule (para. 0241).
As to claim 13, IVANCIC teaches the biomolecule comprises a peptide, a protein, an enzyme, an antibody, an aptamer, DNA, RNA, siRNA, an oligonucleotide, a small molecule, or any combination thereof (para. 0107).
As to claim 14, IVANCIC teaches the sequence of the nucleic acid is obtained by Sanger sequencing, pyrosequencing, reversible terminator chemistry, sequencing by ligation, H+ Ion sensitive transistor, nanopore sequencing, next generation sequencing, or any combination thereof (paras. 0278, 0282 & 0288).
As to claim 15, IVANCIC teaches the biomolecule comprises a peptide, a protein, an enzyme, an antibody, an aptamer, DNA, RNA, siRNA, an oligonucleotide, a small molecule, a drug, or any combination thereof (para. 0107).
As to claim 16, IVANCIC teaches composition comprising, at least a lentiviral particle comprising:
(a) a pol gene nucleic acid sequence encoding a reverse transcriptase sequence comprising a M230I and a Y501W mutation with reference to SEQ ID NO: 1 (paras. 0091-93); and
(b) a heterologous nucleic acid sequence encoding the protein (id.).
As to claim 17, IVANCIC teaches the reverse transcriptase comprises an amino acid sequence as set forth in SEQ ID NO: 14, or a sequence at least about 80% identical thereto (id.).
As to claim 18, IVANCIC teaches method of screening for one or more genomic mutations in a target cell, wherein the one or more genomic mutations confers drug-resistance to a drug (claim 18, paras. 0045, 0146, 0151-54, 0179, 0230, 0248), to the target cell, the method comprising:
(a) transducing the target cell with at least one lentiviral particle comprising a pol gene nucleic acid sequence encoding a reverse transcriptase sequence comprising a M230I and a Y501W mutation with reference to SEQ ID NO: 1 (paras. 0091-93);
(b) contacting the target cell with the drug after step (a), to select for the target cell with the drug resistance, in a target cell population (paras. 0045, 0146, 0151-54, 0179, 0230, 0248);
(c) obtaining the genomic sequence from the target cell with drug resistance (paras. 0045, 0146, 0151-54, 0179, 0230, 0248);
(d) screening for one or more mutations that confer the drug resistance, wherein screening comprises comparing the genomic sequence of the target cell with the drug resistance, to a control genomic sequence obtained from a cell without drug resistance (paras. 0045, 0146, 0151-54, 0179, 0230, 0248).
As to claim 19, IVANCIC teaches the reverse transcriptase comprises an amino acid sequence as set forth in SEQ ID NO: 14, or a sequence at least about 80% identical thereto (paras. 0091-93).
As to claim 20, IVANCIC teaches the drug comprises a drug for treatment of a cancer (paras. 0045, 0146, 0151-54, 0179, 0230, 0248).
As to claim 21, IVANCIC teaches the cancer comprises breast cancer, prostate cancer, lymphoma, skin cancer, pancreatic cancer, colon cancer, melanoma, malignant melanoma, ovarian cancer, brain cancer, primary brain carcinoma, head-neck cancer, glioma, glioblastoma, liver cancer, bladder cancer, non-small cell lung cancer, head or neck carcinoma, breast carcinoma, ovarian carcinoma, lung carcinoma, small-cell lung carcinoma, Wilms' tumor, cervical carcinoma, testicular carcinoma, bladder carcinoma, pancreatic carcinoma, stomach carcinoma, colon carcinoma, prostatic carcinoma, genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma, myeloma, multiple myeloma, adrenal carcinoma, renal cell carcinoma, endometrial carcinoma, adrenal cortex carcinoma, malignant pancreatic insulinoma, malignant carcinoid carcinoma, choriocarcinoma, mycosis fungoides, malignant hypercalcemia, cervical hyperplasia, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, chronic granulocytic leukemia, acute granulocytic leukemia, hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma, polycythemia vera, essential thrombocytosis, Hodgkin's disease, non-Hodgkin's lymphoma, soft-tissue sarcoma, mesothelioma, osteogenic sarcoma, primary macroglobulinemia, retinoblastoma, or any combination thereof (paras. 0045, 0146, 0151-54, 0179, 0230, 0248).
Claim Rejection - 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.
Claim 7-11 and 22 are rejected under 35 U.S.C. § 103 as being unpatentable over IVANCIC (US 20260125669, effective filing 10/7/2022), in view of DALEY (US20030175972).
It would have been prima facie obvious to a person of ordinary skill in the synthetic evolution art before effective filing to apply familiar inducible promotor and cancer genes commonly used in synthetic evolution to screen for mutations and drugs with a reasonable expectation of success.
IVANCIC does not explicitly teach inducible promotor and cancer genes such as those of claims 7-11 and 22. However, IVANCIC suggests to apply the technique therein to these familiar targets. IVANCIC states
More recently, tools and platforms for synthetic evolution have been developed (Simon et al., 2019. Nat Biotechnol. 37(7):730-743; US20030175972 A1; Rossolillo et al., 2012. PLOS Genetics; Yenerall et al., 2021. Cancer Research). In particular, virus-assisted evolution has been developed to trigger the synthetic evolution of individual genes or subset of genes. For instance, the team of David Liu at Harvard has developed “PACE”, for “phage-assisted continuous evolution”, using M13 bacteriophages containing a gene of interest to be evolved, to infect Escherichia coli cells and propagate from one cell to another. With each cycle of infection and propagation, the phage's nucleic acid including the gene of interest is subject to mutations, and phage growth enables the selection of the most active variants (Esvelt et al., 2011. Nature. 472(7344):499-503; WO 2010/028347 A2; WO 2012/088381 A2)
(para. 0005). Among these many examples, US20030175972 demonstrates the routine application of inducible promotors and familiar cancer genes to familiar synthetic evolution platforms.
For example, US20030175972 teaches
In one embodiment, the nucleic acid includes a heterologous insert sequence. The insert sequence can be a sequence of interest, e.g., a polypeptide encoding sequence (e.g., a cDNA, full-length cDNA or genomic DNA), a nucleic acid encoding a ribozyme, a nucleic acid aptmer, a polylinker, and/or a marker protein, e.g., a mammalian marker protein. The marker can be a selectable, counter-selectable, or detectable marker. For example, mammalian selectable markers can include, but are not limited to, kanamycin/G418, hygromycib B or mycophenolic acid resistance markers. Detectable markers can include, but are not limited, a fluorescent marker (e.g., green fluorescent protein, variants thereof, red fluorescent protein, variants thereof, and the like) or a marker which can alter the fluorescence of a cell. In another embodiment, the nucleic acid includes a bacterial selectable marker. Selectable bacterial markers can include, but are not limited to, kanamycin/G418, zeocin, actinomycin, ampicillin, gentamycin, tetracycline, chloramphenicol and penicillin resistance markers. The bacterial marker can be about 600 kb, 550 kb, 500 kb, 450 kb, 400 kb or less in size. The bacterial marker can also include a bacterial promoter, e.g., an Em7 promoter. In one embodiment, the bacterial marker is a bleomycin gene or fragments or mutants thereof.
[ . . . ]
FIG. 13 shows reversion analysis of the pEYK3.1 vector subcloned with the BCR/ABL oncogene. FIG. 13A depicts an integrated B/A pEYK-3.1 provirus flanked by loxP sites. The B/A pEYK3.1 vector renders factor-dependent cell lines into factor-independent cell lines. FIG. 13B is a graph depicting reversion analysis with the B/A pEYK3.1 vector. The B/A pEYK3.1 vector was transformed in the presence of IL-3 with a polycistronic virus which expresses both Cre and the GFP-3M genes. Two days after Cre infection the population was divided in half, one half continued to receive IL-3 while the other half was deprived of IL-3. FACS analysis on the populations two days later demonstrated viability of the GFP-positive population grown in the absence of IL-3 decreased from 100% to 12%.
(paras. 0008 & 0158). Among the variants commonly resulting is insertions and deletions (para. 0297). Thus, Tet-inducible promotors, along with familiar cancer gene like BCR-ABL were routinely applied in synthetic evolution platforms such as in IVANCIC.
In sum, a skilled artisan would have been motivated to apply familiar inducible promotor systems and familiar genes to the familiar synthetic evolution platforms such as in IVANCIC to achieve familiar results.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELODY TSUI whose telephone number is (571)272-1846. The examiner can normally be reached Monday - Friday, 9am - 5pm.
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/YUNG-SHENG M TSUI/ Primary Examiner, Art Unit 1684
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