The present application is being examined under the pre-AIA first to invent provisions.
Claim Objections
Claim 1 is objected to because of the following informalities: The claim recites “IL8B” where it appears “IL8” is intended. Appropriate correction is required.
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 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 pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 1-5, 7-12, and 14 is/are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Tang et al. (Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1089–1102).
The reference teaches a method for detecting differential expression among different cell types.
The method includes isolating subsets of mononuclear cells including T-cells, B-cells, natural killer cells and monocytes from subject whole blood samples using an antibody cocktail. Thus, the reference teaches isolating by using antibodies at least one phagocytic cell and at least one non-phagocytic cell from a whole blood sample from an individual.
Claim 1 sets forth that the gene expression profiles “comprise” the gene expression profile of “each of only” two to twenty-three genes. The use of the open transitional phrase “comprise” means that the claim encompasses methods wherein the expression profiles have the required genes and can also comprise any unlimited number of additional genes.
The reference teaches obtaining a first gene expression profile from two or more markers selected from those listed in claim 1 from the at least one phagocytic cell using a microarray assay and also obtaining a second gene expression profile from two or more markers selected from those listed in claim from the at least one non-phagocytic cell using a microarray assay. Evidence that the in required markers were profiled is given in Figure 4, where results for ETS-2 are reported. Furthermore, it is noted that the differential expression was measured using an Affymetrix U133 Plus2 arrays which inherently includes probes for detecting at least BAK1, EGFR, ERBB2, as evidenced by the Affymetrix search for these genes (SEE IDS 6/15/23). The method taught by Tang et al. inherently obtained the expression profile of two or more markers, as the microarray contained probes for measuring expression of these markers.
Following this, Tang et al. teaches the entirety of the method set forth in claim 1.
Regarding claim 2, the markers assayed by Tang et al. are RNA markers.
Regarding claim 3, the phagocytic cell is a monocyte.
Regarding claim 4, the non-phagocytic cell is a T-cell.
Regarding 9, the cells were isolated form a population of white blood cells (1091).
Regarding claims 5, 7, 10 and 12 the cells were isolated using an antibody cocktail (p. 1091). The antibodies inherently bind to receptors that are expressed on the plasma membranes of the separate WBC populations.
Regarding claims 8 and 11, the reference teaches that neutrophils were separated from other cells (which includes non-phagocytic cells) by centrifugation in leukocyte separation media, which is a gradient based centrifugation (p. 1091).
With regard to claim 14, the gene expression profiles were obtained in the reference by microarray assay, which is also a hybridization assay.
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 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claim 1-5, 7-13, and 15 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Visser et al. (Nature Reviews, Volume 6, January 2006, pages 24-37) in view of Tang et al. Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1089–1102, as evidenced by the Probeset listing for Human Genome U133 Plus 2.0 array.
De Visser teach that each stage of cancer development is susceptible to regulation by immune cells. Full activation of adaptive immune cells in response to tumor might result in eradication of malignant cells, but chronic activation of innate immune cells in or around pre-malignant tissues might actually promote tumor development. Innate immune cells include phagocytic and non-phagocytic cells, including dendritic cells, macrophages, neutrophils and basophils, and are the first line of defense against foreign pathogens. Acute activation of innate immunity sets the stage for activation of the adaptive immune system which includes T cells and B cells.
De Visser et al. does not teach a method in which expression profiles of different types of immune cells are obtained from an individual diagnosed having primary cancer and compared the expression in the different types of immune cells to one another.
Tang et al. teach that since there is substantial evidence for an inflammatory-immune response to ischemic stroke, gene expression profiles in the blood of rats subject to a variety of phenotypes was obtained. Tang et al. teach a method for detecting differential expression among different cell types.
The method includes isolating subsets of mononuclear cells including T-cells, B-cells, natural killer cells and monocytes from subject whole blood samples using an antibody cocktail. Thus, the reference teaches isolating by using antibodies at least one phagocytic cell and at least one non-phagocytic cell from a whole blood sample from an individual.
Claim 1 sets forth that the gene expression profiles “comprise” the gene expression profile of “each of only” two to twenty-three genes. The use of the open transitional phrase “comprise” means that the claim encompasses methods wherein the expression profiles have the required genes and can also comprise any unlimited number of additional genes.
The reference teaches obtaining a first gene expression profile from two or more markers selected from those listed in claim 1 from the at least one phagocytic cell using a microarray assay and also obtaining a second gene expression profile from two or more markers selected from those listed in claim from the at least one non-phagocytic cell using a microarray assay. Evidence that the one of the required markers were profiled is given in Figure 4, where results for ETS2 are reported. Furthermore, it is noted that the differential expression was measured using an Affymetrix U133 Plus2 arrays which also inherently includes probes for detecting at least ATM and CDC25A (see page 87 and 94 of the Probeset listing for Human Genome U133 Plus 2.0 array attached herewith). Furthermore, the array included probes for detecting BAK1, EGFR, and ERBB2, see probeset listing at pages 88, 107, and 109. The method taught by Tang et al. inherently obtained the expression profile of two or more markers, as the microarray contained probes for measuring expression of these markers.
Regarding claim 2, the markers assayed by Tang et al. are RNA markers.
Regarding claim 3, the phagocytic cell is a monocyte.
Regarding claim 4, the non-phagocytic cell is a T-cell.
Regarding 9, the cells were isolated form a population of white blood cells (p. 1091).
Regarding claims 5, 7, 10 and 12 the cells were isolated using an antibody cocktail (p. 1091). The antibodies inherently bind to receptors that are expressed on the plasma membranes of the separate WBC populations.
Regarding claims 8 and 11, the reference teaches that neutrophils were separated from other cells (which includes non-phagocytic cells) by centrifugation in leukocyte separation media, which is a gradient based centrifugation (p. 1091).
Although Tang et al. do not separate out different cell types and detect expression in each cell type in an individual having stroke, they do expressly suggest that such a study should also be carried out (p. 1089).
It would have been prima facie obvious to have modified the teachings of DeVisser et al. so as to have carried out a study similar to that taught by Tang et al. in patients that have previously diagnosed cancer and in healthy controls, and further to determine expression in cellular fractions of different types of immune cells in both a healthy control and a patient with cancer to determine which types of cells are involved in the human blood genomic responses to cancer and to confirm the results, as taught by Tang for stroke, a different disease with an immune component to the response. One would have been motivated to undertake such a study to better understand genomic changes in peripheral blood cells in response to the presence of diseases. Tang et al. teach that the genomic changes that occur in leukocytes during the time after stroke should help understand the process in humans- and the same would be relevant to cancer. Better understanding of how circulating immune cells are expressing genes in patients having cancer will help better understand the process in human. Such a method would inherently include identifying differentially expressed genes among the different cell types.
Claim 6 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Visser in view of Tang et al., as applied to claims 1-5, 7-12, and 15 above, and further in view of in view of Drach et al. (Blood, Vol80, No 11 (December 1). 1992: pp 2729-2734).
The teachings of DeVisser in view of Tang et al. as they are relevant to claim 1, from which claim 6 depends are given previously in this office action and are fully incorporated here.
Tang et al. does not teach separating the blood cell populations by fluorescence activated cell sorting (FACS).
Drach et al. teach using FACS to sort lineage-specific stained blood cells, including sorting T-cells and monocytes from one another (p. 2731).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have modified the method taught by Tang et al. so as to have employed FACS in the separation of cell populations for gene expression analysis. Both references teach methods for separating blood cell populations for analysis of gene expression and comparison of populations. It would have been obvious to one skilled in the art to substitute one method for the other to achieve the predictable result of separating the cell populations because the substitution of one known element to achieve the same, predictable function is prima facie obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Juliet Switzer
Primary Examiner
Art Unit 1634
/JULIET C SWITZER/Primary Examiner, Art Unit 1634
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