11229382 (B.P.A.I. Aug. 30, 2010)

Ex Parte Ghosh et al

Board of Patent Appeals and InterferencesAug 30, 2010

11229382 (B.P.A.I. Aug. 30, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/229,382 09/16/2005 Richik N. Ghosh 97,022-N2-D 9993 7590 08/31/2010 David S. Harper McDonnell Boehnen Hulbert & Berghoff 31st Floor 300 S. Wacker Drive Chicago, IL 60606 EXAMINER COOK, LISA V ART UNIT PAPER NUMBER 1641 MAIL DATE DELIVERY MODE 08/31/2010 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte RICHIK N. GHOSH, ROBBIN DEBIASIO, and PREM JANARDHAN __________ Appeal 2009-009745 Application 11/229,382 Technology Center 1600 __________ Before DONALD E. ADAMS, DEMETRA J. MILLS, and MELANIE L. McCOLLUM, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL1 This is an appeal under 35 U.S.C. § 134. The Examiner has rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). 1 The two-month time period for filing an appeal or commencing a civil action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE” (paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery mode) shown on the PTOL-90A cover letter attached to this decision. Appeal 2009-009745 Application 11/229,382 2 STATEMENT OF CASE The following claim is representative. 1. An automated method for analyzing neurite outgrowth comprising: (a) providing an array of locations comprising cells, wherein the cells possess at least a first luminescently labeled reporter molecule that reports on cell location, and at least a second luminescently labeled reporter molecule that reports on neurite outgrowth, and wherein the cells comprise neurons; (b) obtaining a nuclear image from the at least first luminescently labeled reporter molecule and a neurite image from the at least second luminescently labeled reporter molecule; (c) automatically identifying cell bodies from the nuclear image; (d) automatically identifying neurites extending from the cell bodies by identifying pixels in the neurite image that are not present in the nuclear image, wherein said pixels define neurites extending from the cell bodies; and (e) automatically determining one or more features of the defined neurites. Cited References Dunlay et al. WO 98/38490 Sept 3, 1998 Ramakers et al., Depolarization stimulates lamellipodia formation and axonal but not dendrtic branching in cultured rat cerebral cortex neurons, 108 DEVELOPMENT BRAIN RESEARCH 205-216 (1998). Mamoru Sano, Nerve growth factor-responsive, transcription-independent outgrowth of neuritis in a clonal variant of PC12 cells (PC12D), 1 CURRENT TOPICS IN NEUROCHEMISTRY 27-40 (Abstract only) (1997). Ranefall et al., A new method for segmentation of colour images applied to immunohistochemically stained cell nuclei, 15 ANALYTICAL CELLULAR PATHOLOGY 145-156 (1997). Appeal 2009-009745 Application 11/229,382 3 Grounds of Rejection 1. Claims 1, 4, 5, 7, 8, 9, 17, 18, and 21-22 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Ramakers et al. in view of Dunlay et al. 2. Claims 12-14 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Ramakers et al. in view of Dunlay et al. and in further view of Ranefall et al. 3. Claims 2, 3 and 6 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Ramakers et al. in view of Dunlay et al. and in further view of Sano. Discussion ISSUE The Examiner concludes that It would have been obvious to one of ordinary skill in the art at the time the invention was made to measure neurite outgrowth as taught by Ramakers et al. in the method of Dunlay et al. because Dunlay et al. taught that their method allowed for multicolored fluorescence of multiple targets and cells to be assayed in a single screen. See page 16 2nd paragraph. In the procedure of Dulany et al. the HCS is directly coupled to HTS to allow for the screening of a large number of compounds. See page 20 - 2nd paragraph and page 21. Further, this analysis can be used to label not only specific components within specific cells but also specific cells within a population of mixed cell types. See page 27 lines 14-18, for example. Therefore one of ordinary skill would be motivated to measure neurite outgrowth images as taught by Ramakers et al. in the method of Dunlay et al. in order to quickly generate data images of a cell for precise and accurate evaluation of the cell and its components. One of ordinary skill would have expected the combination of Ramakers et al. in view of Dunlay et al. to be Appeal 2009-009745 Application 11/229,382 4 successful because both references teach cell imaging analysis procedures. (Ans. 6-7.) Appellants contend that the combination of Ramakers and Dunlay fails to teach or suggest identifying neurites extending from cell bodies by identifying pixels in a neurite image that are not present in a nuclear image (i.e., step (d) of claims 1 and 18). This step involves comparing a nuclear image of a cell to a neurite image of the same cell. Ramakers fails to disclose the use of two separate reporter molecules to identify neurites. Instead, Ramakers discloses the use of only a single cellular stain, DiI, which is used to identify all of the various structures of a neuron. See section 2.3, p. 207; and Fig. 1. DiI is a lipophilic membrane stain, and thus it stains the membrane of the neuron cell body and the neurites. See Exhibit 1. Moreover, Dunlay does not contain any express disclosure of neurite outgrowth. (App. Br. 5.) The issue is: Do the cited references suggest claim step (d), automatically identifying neurites extending from the cell bodies by identifying pixels in the neurite image that are not present in the nuclear image, wherein said pixels define neurites extending from the cell bodies? PRINCIPLES OF LAW An invention “composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). “Often, it will be necessary . . . to look to interrelated teachings of multiple [references] . . . and the background knowledge possessed by a Appeal 2009-009745 Application 11/229,382 5 person having ordinary skill in the art, all in order to determine whether there was an apparent reason to combine the known elements in the fashion claimed[.]” Id. “[T]his analysis should be made explicit” (id.), and it “can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does” (id.). “[T]here must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). Moreover, “obviousness requires a suggestion of all limitations in a claim.” CFMT, Inc. v. Yieldup Int’l. Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003) (citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)). When evaluating claims for obviousness, “the prior art as a whole must be considered. The teachings are to be viewed as they would have been viewed by one of ordinary skill.” In re Hedges, 783 F.2d 1038, 1041 (Fed. Cir. 1986). FINDINGS OF FACT 1. The Examiner finds that Ramakers et al. disclose automated image procedures to measure neuronal cell growth cone morphology and neurite outgrowth. See abstract, page 207, and figure 1. The neurons were labeled with DiI stain and analyzed with a Zeiss 410 confocal microscope at a resolution of 1024 x 1024 pixels. See page 207, 2nd column section 2.3. The cells were tested for the effects of depolarization with 25mM potassium chloride. This caused rapid increase of the surface area in most growth cones (stimulus). See page 209 lst column section 3. Appeal 2009-009745 Application 11/229,382 6 (Ans. 5.) 2. “Ramakers et al. differ from the instant invention in not specifically teaching the use of multiple luminescently labeled report molecules.” (Ans. 5.) 3. The Examiner finds that Dunlay et al. teach automated procedures to analyze cell components with multiphoton microscope imaging. See page 8, for example. The multicolored fluorescence permits multiple targets and cells to be assayed in a single screen. The HCS component can be used to measure the effects of drugs, cell function, locomotion, and cell-cell communication. See page 16 2nd paragraph. The HCS is directly coupled to HTS to allow for the screening of a large number of compounds. See page 20 - 2nd paragraph and page 21. (Id.) 4. The Examiner finds that, in Dunlay The array is imaged at a low resolution of a few microns per pixel and particular locations are imaged at a higher resolution of less than 0.5 microns per pixel. These two resolutions modes help to improve the overall throughput of the system. See page 19, 3rd paragraph. In preferred embodiments the methods include computerized means for acquiring, processing, displaying, and storing the data received. See page 10. (Id. at 5-6.) 5. The Examiner finds that, in Dunlay On page 12, machine- readable storage mediums are discussed. These measurements can be used to determine the distribution, environment or activity of the fluorescent reporter molecule within the cells (claim 17). See page 23 - 2nd paragraph and page 26. The data analysis involves imaging a primary marker Appeal 2009-009745 Application 11/229,382 7 (typically cell nuclei counter stained with DAP or PI fluorescent dyes). Pages 24-28, Fluorescence Reporter Molecules; especially page 27 lines 7-18, and page 32. The array is also labeled with a detectable marker for the cytoplasm and imaged to produce a cytoplasmic mask. (Ans. 6.) 6. The Examiner finds that The data from each pair of images obtained from each well in the array can be used to measure each object in the image field (e.g. cells and nuclei) and calculate its size, shape, and integrated intensity. See page 57 lines 16-21. This analysis can be used to label not only specific components within specific cells but also specific cells within a population of mixed cell types. See page 27 lines 14-18, for example. (Id.) 7. The Examiner finds that It would have been obvious to one of ordinary skill in the art at the time the invention was made to measure neurite outgrowth as taught by Ramakers et al. in the method of Dunlay et al. because Dunlay et al. taught that their method allowed for multicolored fluorescence of multiple targets and cells to be assayed in a single screen. See page 16, 2nd paragraph. In the procedure of Dulany et al. the HCS is directly coupled to HTS to allow for the screening of a large number of compounds. See page 20 - 2nd paragraph and page 21. Further, this analysis can be used to label not only specific components within specific cells but also specific cells within a population of mixed cell types. See page 27 lines 14-18, for example. (Id.) 8. The Examiner finds that Therefore one of ordinary skill would be motivated to measure neurite outgrowth images as taught by Ramakers et al. Appeal 2009-009745 Application 11/229,382 8 in the method of Dunlay et al. in order to quickly generate data images of a cell for precise and accurate evaluation of the cell and its components. One of ordinary skill would have expected the combination of Ramakers et al. in view of Dunlay et al. to be successful because both references teach cell imaging analysis procedures. (Ans. 7.) 9. “Ramakers et al. in view of Dunlay et al. differ from the instant invention in not specifically teaching the contacting of the cells with a control compound to stimulate neurite outgrowth and further analyze a tests compounds ability to inhibit neurite outgrowth.” (Id.) 10. “However, Sano disclose this limitation. Specifically, Sano teach the utility of PC12 cells, which are NFG-dependent for neurite outgrowth. A MEK inhibitor - PD-98059, inhibited the neurite outgrowth. See abstract.” (Id.) 11. The Examiner finds that It would have been obvious to one of ordinary skill in the art at the time the invention was made to measure neurite outgrowth with a control compound to stimulate said outgrowth and further analyze a test compound for inhibition as taught by Sano in the method of Ramakers et al. in view of Dunlay et al. because Sano taught that this procedure provided predictable neurite outgrowth that allowed for discrimination of inhibitor pathways. See abstract. (Id.) 12. “Ramakers et al. (Developmental Brain Research, 108, 1998, pages 205-216) in view of Dunlay et al. (WO 98/38490) differ from the instant invention in not specifically teaching nuclear imaging including dilations of Appeal 2009-009745 Application 11/229,382 9 the kernel (central or initial nuclear image for further identification.” (Ans. 8.) 13. The Examiner finds that Ranefall et al. disclose that segmented images (dilations of the kernel image) of stained nuclei can distinguish positive staining reaction from other cell nuclei. See abstract. The full nuclear image is split and spread to more clearly identify the stained cells. See page 146. It would have been obvious to one of ordinary skill in the art at the time the invention was made to measure segmented images (dilations of the kernel image) of stained nuclei as taught by Ranefall et al. in the method of Ramakers et al. in view of Dunlay et al. because Ranefall et al. taught that this procedure improved reproducibility and more accurately identified positive nuclei. Page 155 Discussion. (Id.) ANALYSIS According to the Examiner It would have been obvious to one of ordinary skill in the art at the time the invention was made to measure neurite outgrowth as taught by Ramakers et al. in the method of Dunlay et al. because Dunlay et al. taught that their method allowed for multicolored fluorescence of multiple targets and cells to be assayed in a single screen. See page 16 2nd paragraph. In the procedure of Dulany et al. the HCS is directly coupled to HTS to allow for the screening of a large number of compounds. See page 20 - 2nd paragraph and page 21. Further, this analysis can be used to label not only specific components within specific cells but also specific cells within a population of mixed cell types. See page 27 lines 14-18, for example. Therefore one of ordinary skill would be motivated to measure neurite outgrowth images as taught by Ramakers et al. in the method of Dunlay et al. in order to quickly generate data Appeal 2009-009745 Application 11/229,382 10 images of a cell for precise and accurate evaluation of the cell and its components. One of ordinary skill would have expected the combination of Ramakers et al. in view of Dunlay et al. to be successful because both references teach cell imaging analysis procedures. (Ans. 6-7.) Appellants contend that the combination of Ramakers and Dunlay fails to teach or suggest identifying neurites extending from cell bodies by identifying pixels in a neurite image that are not present in a nuclear image (i.e., step (d) of claims 1 and 18). This step involves comparing a nuclear image of a cell to a neurite image of the same cell. Ramakers fails to disclose the use of two separate reporter molecules to identify neurites. Instead, Ramakers discloses the use of only a single cellular stain, DiI, which is used to identify all of the various structures of a neuron. See section 2.3, p. 207; and Fig. 1. DiI is a lipophilic membrane stain, and thus it stains the membrane of the neuron cell body and the neurites. See Exhibit 1. Moreover, Dunlay does not contain any express disclosure of neurite outgrowth. (App. Br. 5.) We essentially agree with the Appellants arguments as set forth in the Brief. The Examiner has failed to adequately explain where the prior art suggests step (d), automatically identifying neurites extending from the cell bodies by identifying pixels in the neurite image that are not present in the nuclear image, wherein said pixels define neurites extending from the cell bodies. Appeal 2009-009745 Application 11/229,382 11 CONCLUSION OF LAW The cited references do not support the Examiner’s obviousness rejection and do not disclose step (d) as claimed. 2. Claims 12-14 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Ramakers et al. in view of Dunlay et al. and in further view of Ranefall et al. 3. Claims 2, 3 and 6 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Ramakers et al. in view of Dunlay et al. and in further view of Sano. Appellants traverse these rejections for the same reasons as the primary rejection. (See App. Br. 6.) For the reasons given for rejection 1, we reverse these rejections. REVERSED cdc DAVID S. HARPER MCDONNELL BOEHNEN HULBERT & BERGHOFF 31ST FLOOR 300 S. WACKER DRIVE CHICAGO, IL 60606