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
Summary
Claims 1-18 have been examined and fully considered.
Claim Objections
Claims 7, 13, and 15 are objected to because of the following informalities:
Claim 7 is objected to since abbreviation (DMNT1) should read as “(DNMT)” in the last line.
Claim 13 recites “the candidate therapeutic”. It should read as “the candidate therapeutic agent”.
Claim 15 recites “the candidate therapeutic”. It should read as “the candidate therapeutic agent”.
Appropriate correction is required.
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.
Claim 9 is 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 9 recites the limitation "the second cellular analyte". There is no mention of “a second cellular analyte” in claims 1 and 8 upon which claim 9 depends. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Ornatsky et al. (US 20080193930) in view of Cruz-Moura et al. (US 20170119804).
Regarding Claim 1, Ornatsky teaches a method of analyzing a population of biological cells that includes cycling cells (G1) and non- cycling cells (G0) (Paragraph 0015), then determining DNA content of individual biological cells in the population such that cells having a 2N DNA content are identified (Paragraph 0051).
Ornatsky does teach an analyte to differentiate G1/S and G2/M (Paragraph 0051) and teaches identifying a first cellular analyte (first element) in a cell sample that will distinguishes the sample independent of the first cellular analyte (first element) (Paragraph 0031), however, Ornatsky does not teach an analyte to distinguish cell in the G0 and G1 cell cycle phases.
However, Cruz-Moura teaches for cells having the 2N DNA content and distinguishing cells in G1 phase of the cell cycle from cells in GO phase of the cell cycle (Paragraph 0191), for the benefit of distinguishing how many cells are in the quiescent state (G0) to see the effects of a therapeutic agent. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with an analyte that distinguishes the cell in the G0/G1 phases as taught by Cruz-Moura for the benefit of determining the effects of a therapeutic agent in cells in the quiescent state (G0).
Regarding Claim 2, Ornatsky teaches the method as shown above, but does not teach that a population of biological cells includes cells from blood.
This is remedied by Cruz-Moura which teaches that the population of biological cells includes cells from blood (Paragraph 0179) for the benefit of comparing the analyte expression in blood samples from individuals with and without acute myeloid leukemia.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to obtain biological cells from blood due to the fact that blood cell samples allow the study of analyte expression in healthy individuals in comparison to non-healthy individuals.
Regarding Claim 3, Ornatsky teaches the method as shown above, but does not teach that a population of biological cells includes mononuclear cells.
However, Cruz-Moura teaches that the population of biological cells includes mononuclear cells (Paragraph 0179) for the benefit of comparing the effects of analyte expression in mononuclear cells to nuclear cells.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to obtain biological cells that include mononuclear cells due to the fact that mononuclear cells need to be studied for the effects of analyte expression in comparison to nuclear cells.
Regarding Claim 4, Ornatsky teaches determining DNA content on a single-cell basis (Paragraph 0037).
Regarding Claim 5, Ornatsky teaches identifying a second cellular analyte (second element) in a cell sample that will distinguishes the sample independent of the second cellular analyte (second element) (Paragraph 0031), however, Ornatsky does not teach an analyte to distinguish cell in the G0 and G1 cell cycle phases.
However, Cruz-Moura teaches distinguishing cells in G1 phase of the cell cycle from cells in GO phase of the cell cycle (Paragraph 0191), for the benefit of distinguishing how many cells are in the quiescent state to see the effects of a therapeutic agent. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with an analyte that distinguishes the cell in the G0/G1 phases as taught by Cruz-Moura for the benefit of determining the effects of a therapeutic agent in cells in the quiescent state.
Regarding Claim 6, Ornatsky teaches the method as shown above but does not teach the second cellular analyte being Ki-67.
However, Cruz-Moura teaches the cellular analyte being Ki-67 (Paragraph 0191), for the benefit of distinguishing how many cells in the population are in G0 and G1 cell cycle phase. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with Ki-67 as the secondary cellular analyte as taught by Cruz-Moura for the benefit of distinguishing the cell in the G0/G1 phases.
Regarding Claim 7, Ornatsky teaches the method as shown above but does not teach the first cellular analyte being DNA methyltransferase.
However, Cruz-Moura teaches the cellular analyte being DNA methyltransferase (Paragraph 0023), for the benefit of determining the effect of DNA methylation in gene expression. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with DNA methyltransferase as the first cellular analyte as taught by Cruz-Moura for the benefit of determining the effect of DNA methylation in gene expression.
Regarding Claim 8, Ornatsky teaches a population of biological cells has been treated with a candidate therapeutic agent (Paragraph 0004).
Regarding Claim 9, Ornatsky teaches a population of biological cells has been treated with a candidate therapeutic agent wherein the candidate therapeutic agent affects levels of the first cellular analyte and does not affect levels of the second cellular analyte (Paragraph 0004). Ornatsky reads on how “DNA intercalating reagents” are commonly used are therapeutic agents because of their “site selective targeting and reactivity” (Paragraph 0004).
Regarding Claim 10, Ornatsky teaches a population of biological cells has been treated with a candidate therapeutic agent, however, it does not include the candidate therapeutic agent including azacytidine or decitabine.
However, Cruz-Moura teaches that candidate therapeutic agent could include azacytidine or decitabine (Paragraph 0023) for the benefit of inhibiting enzymes that catalyze the methylation reaction. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with the candidate therapeutic agent including azacytidine or decitabine as taught by Cruz-Moura for the benefit of inhibiting the effect of DNA methylation in gene expression.
Regarding Claim 11, Ornatsky teaches a method of providing a population of cells that has been exposed to a candidate therapeutic agent (Paragraph 0004), fixing and/or permeabilizing the population of cells (Paragraph 0028), staining the population of cells for DNA content, for a first cellular analyte that is differentially expressed in cycling cells as compared to non-cycling cells, and for a second cellular analyte (Paragraph 0031); and analyzing the stained cells (Paragraph 0031). Ornatsky doesn’t teach distinguishing the cycling cells from the non-cycling cells, based on detection of the first analyte in the stained cells and detecting the second analyte in the cycling cells exclusive of the non-cycling cells, or in the non-cycling cells exclusive of the cycling cells.
However, Cruz-Moura teaches a method for distinguishing the cycling cells from the non-cycling cells, based on detection of the first analyte in the stained cells and detecting the second analyte in the cycling cells exclusive of the non-cycling cells, or in the non-cycling cells exclusive of the cycling cells (Paragraph 0191) with the motivation of distinguishing how many cells are in the quiescent state (G0) to see the effects of a therapeutic agent. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with the method of distinguishing cycling and non-cycling cells as taught by Cruz-Moura for the benefit of distinguishing how many cells are in the quiescent state (G0) to see the effects of a therapeutic agent.
Regarding Claim 12, Ornatsky teaches that a population of cells in includes cycling cells and non-cycling cells (Paragraph 0015).
Regarding Claim 13, Ornatsky teaches a method of providing a population of cells that has been exposed to a candidate therapeutic agent (Paragraph 0004), however, it does not teach that the candidate therapeutic agent includes a DNA methyltransferase inhibitor.
However, Cruz-Moura teaches that candidate therapeutic agent includes a DNA methyltransferase inhibitor (Paragraph 0005) for the benefit of inhibiting the effect of DNA methylation in gene expression. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with a candidate therapeutic agent which includes a DNA methyltransferase inhibitor as taught by Cruz-Moura for the benefit of inhibiting enzymes that catalyze the methylation reaction.
Regarding Claim 14, Ornatsky teaches identifying a first cellular analyte (first element) in a cell sample that will distinguishes the sample independent of the first cellular analyte (first element) (Paragraph 0031), however, Ornatsky does not teach an analyte to distinguish cell in the G0 and G1 cell cycle phases.
However, Cruz-Moura teaches distinguishing cells in G1 phase of the cell cycle from cells in GO phase of the cell cycle (Paragraph 0191), for the benefit of distinguishing how many cells are in the quiescent state (G0) to see the effects of a therapeutic agent. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with an analyte that distinguishes the cell in the G0/G1 phases as taught by Cruz-Moura for the benefit of determining the effects of a therapeutic agent in cells in the quiescent state (G0).
Regarding Claim 15, Ornatsky teaches a method of providing a population of cells that has been exposed to a candidate therapeutic agent (Paragraph 0004), however, Ornatsky does not teach the first cellular analyte not being affected by the candidate therapeutic.
However, Cruz-Moura teaches that candidate therapeutic agent includes a DNA methyltransferase inhibitor which wouldn’t affect the first cellular analyte as long it is not DNA methyltransferase (Paragraph 0005) for the benefit of not inhibiting the effect of DNA methylation in gene expression due to the first cellular analyte. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with candidate therapeutic agent includes a DNA methyltransferase inhibitor which wouldn’t affect the first cellular analyte as long it is not DNA methyltransferase as taught by Cruz-Moura for the benefit of determining the effects of DNA methylation in gene expression due to the first cellular analyte.
Regarding Claim 16, Ornatsky teaches identifying a first cellular analyte (first element) in a cell sample, however, Ornatsky doesn’t teach wherein the first cellular analyte is selected from the group consisting of Ki-67, DNA polymerase, thymidine kinase, dihydrofolate reductase, cdc6, HsOrc1, and MCM5.
However, Cruz-Moura remedies this by teaching a cellular analyte called Ki-67 (Paragraph 0191), for the benefit of distinguishing how many cells in the population are in G0 and G1 cell cycle phase. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with Ki-67 as the first cellular analyte as taught by Cruz-Moura for the benefit of distinguishing the cell in the G0/G1 phases.
Regarding Claim 17, Ornatsky teaches the method as shown above with a second cellular analyte but does not teach the second cellular analyte being DNA methyltransferase.
However, Cruz-Moura teaches DNA methyltransferase being cellular analyte (Paragraph 0023), for the benefit of determining the effect of DNA methylation in gene expression. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ornatsky with DNA methyltransferase as the second cellular analyte as taught by Cruz-Moura for the benefit of determining the effect of DNA methylation in gene expression.
Regarding Claim 18, Ornatsky teaches analyzing the stained cells using a single-cell method such as Flow Cytometry (Paragraph 0051).
“Single-cell method” has been interpreted in light of the specification to include “flow cytometry, microscopic imaging, single-cell sequencing, and the like” (see Spec., [077]).
Conclusion
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/H.R.B./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798