Ex Parte Weissman et alDownload PDFPatent Trial and Appeal BoardMay 27, 201612447634 (P.T.A.B. May. 27, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/447,634 04/14/2010 Irving L. Weissman 77974 7590 06/01/2016 Stanford University Office of Technology Licensing Bozicevic, Field & Francis LLP 1900 University Avenue Suite 200 East Palo Alto, CA 94303 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 ATTORNEY DOCKET NO. CONFIRMATION NO. STAN-501 5395 EXAMINER BEL YA VSKYI, MICHAIL A ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 06/01/2016 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address( es): docket@bozpat.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte IRVING L. WEISSMAN, AGNIESZKA CZECHOWICZ, DEEPTA BHATTACHARYA, DANIEL KRAFT 1 Appeal2013-008633 Application 12/447,634 Technology Center 1600 Before DONALD E. ADAMS, JEFFREYN. FREDMAN, and TA WEN CHANG, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to methods of stem cell engraftment in a mammal, which have been rejected as anticipated. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE According to the Specification, "[i]mproved methods for engraftment of stem cells, including hematopoietic stem cells, are of great clinical 1 Appellants identify the Real Party in Interest as the Board of Trustees of the Leland Stanford Junior University. (Br. 1.) Appeal2013-008633 Application 12/447,634 interest." (Spec. i-f 11.) Appellants' inventions relate to "[m]ethods ... for the engraftment of stem cells ... where endogenous stem cells are selectively ablated, thereby opening a niche for the engraftment of donor stem cells." (Id. at i-f 12.) Further according to the Specification, (Id.) [t]he efficiency of engraftment is significantly enhanced by selective ablation, as compared to engraftment obtained without pretreatment. Such selective ablation [also] allows improved function of the targeted tissue during the engraftment period, compared to methods involving non-selective ablation. Claims 1-5, 13, 15, 17-24 are on appeal. Claim 1 is illustrative and reads as follows: 1. A method of stem cell engraftment in a mammal, the method comprising: contacting said mammal with an antibody that selectively binds c-kit and interferes with growth factor signaling essential for hematopoietic stem cell growth or maintenance to selectively ablate endogenous stem cells in a targeted tissue; introducing exogenous stem cells to said mammal after a period of time sufficient to substantially eliminate said antibody from the patient circulation. The claims stand rejected as follows: Claims 1-5, 13, 21, and 22 are rejected under 35 U.S.C. § 102(b) as anticipated by Ishikawa. 2, 3 2 Fumihiko Ishikawa et al., An assay for long-term engrafting human hematopoietic cells based on newborn NOD/SCID/fJ2-microglobulinnull mice, 30 EXPERIMENTAL HEMATOLOGY 488 (2002). 3 In the Answer, the Examiner withdrew the rejection of claims 15, 17-20, 23, and 24 under 35 U.S.C. § 102(b) as being anticipated by Ishikawa. (Ans. 3.) 2 Appeal2013-008633 Application 12/447,634 Claims 1-5, 13, 15, and 17-24 are rejected under 35 U.S.C. § 102(b) as anticipated by Down.4 I. Issue The Examiner has rejected claims 1-5, 13, 21, and 22 under 35 U.S.C. § 102(b) as anticipated by Ishikawa. The Examiner finds that Ishikawa "administer[s] the same amount of the same anti-c-kit antibody, i.e., ACK2 mAb, as used in the instant Specification for the same purpose, i.e., to selectively ablate endogenous stem cells" and thus inherently anticipates the claims at issue. (Ans. 4.) Appellants contend that Ishikawa does not anticipate the claims at issue because it does not disclose selective ablation of endogenous stem cells. (Br. 2-3.) In particular, Appellants argue that Ishikawa only teaches using ACK2 together with other, non-selective ablative agents. (Id. at 3.) Appellants also contend that Ishikawa fails to teach providing exogenous stem cells to a patient after a period of time "sufficient to substantially eliminate the anti-c-kit antibody from the patient circulation" (claim 1) and/or such that "the antibody is present at a concentration of less than 10 ng/ml in the bloodstream" (claim 2), because Ishikawa teaches transplanting cells 24 hours after administering the antibody. (Id. at 3--4.) The issue with respect to this rejection is whether the evidence of record supports the Examiner's finding that Ishikawa anticipates claims 1 and2. 4 Down et al., W02004/002425 A2, published Jan. 8, 2004. 3 Appeal2013-008633 Application 12/447,634 Findings of Fact FF 1. Ishikawa teaches a "quantitative method for analysis of human hematopoietic stem cells." (Ishikawa Abstract.) FF2. Ishikawa teaches conditioning regimens using ACK-2, an anti- c-kit antibody, in combination with cancer drugs 5-fluorouracil or busulfan. (Id. at 489.) FF3. Ishikawa teaches ACK-2 as a neutralizing antibody for mouse c- kit receptor with relatively specific bone marrow suppression. (Id. at 490.) FF4. Ishikawa teaches transplanting human cord blood mononuclear cells into mice 24 hours after the conditioning regimen and observed multi- potential progenitors post-transplantation. (Id. at 489, 493.) FF5. The Specification discloses an embodiment of the invention having ACK2 as the c-kit-binding antibody. (Spec. Example 1.) The Specification discloses that ACK2 inhibits stem cell factor mediated stem cell proliferation, selectively depletes hematopoietic stem cells, and enhances donor stem cell engraftment. (Id. at i-fi-f 18-19, Example 1.) FF6. The Specification describes the time for clearance of an ablative agent as "usually the time sufficient for the level of ablative agent to decrease a[ t] least about 10-fold from peak levels, usually at least about 100- fold, 1000-fold, 10,000 fold, or more." (Id. at i129.) The Specification further states: As used herein, the term "substantially eliminate" when referring to antibodies may provide for a concentration of less than about 10 ng/ml present in the bloodstream. Alternatively, a sample of patient blood or serum may be tested for in vitro cytotoxicity of exogenous stem cells, for example wherein not 4 Appeal2013-008633 Application 12/447,634 more than about 1 % of the stem cells present in a sample are killed after exposure to said patient blood or serum sample. (Id. at iT 67.) Principles of Law "' [I]t is elementary that the mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not cause a claim drawn to those things to distinguish over the prior art. Additionally, where the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on."' In re Best, 562 F.2d 1252, 1254--55, (CCPA 1977) (quoting In re Swinehart, 439 F.2d 210, 212-13 (CCPA 1971)). See also In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990) ("[W]hen the PTO shows sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not."). Analysis Claim 1 is directed to a method of stem cell engraftment comprising (1) contacting a mammal with an antibody with particular characteristics and (2) introducing stem cells to the mammal after a period of time sufficient to substantially eliminate the antibody from the mammal's circulation. Claim 2 additionally requires that the period of time be such that the antibody is present at a concentration of less than 10 ng/ml in the bloodstream. 5 Appeal2013-008633 Application 12/447,634 Ishikawa teaches transplanting human stem cells into mice. (FF4.) It teaches conditioning regimens using ACK-2, an antibody also used in an embodiment in the Specification, and further teaches that ACK-2 is a neutralizing antibody for c-kit receptor with relatively specific bone marrow suppression. (FF2, FF3, FF5.) Ishikawa also teaches transplanting stem cells 24 hours after the conditioning regimen. (FF4.) We find that the evidence of record supports the Examiner's position that Ishikawa anticipates claim 1. Appellants argue that Ishikawa does not disclose selective ablation of endogenous stem cells because Ishikawa teaches using other, non-selective ablative agents together with ACK2. 5 (Br. 2-3.) This argument is not persuasive. As the Examiner points out, the claim is to a method comprising an antibody that selectively ablates; thus, it does not preclude the use of other, non-ablative agents together with such an antibody. (Ans. 4.) Appellants also contend that Ishikawa does not teach providing exogenous stem cells to a patient after a period of time "sufficient to substantially eliminate [the ablating] antibody from the patient circulation" (claim 1) or "such that the antibody is present at a concentration of less than 10 ng/ml in the bloodstream" (claim 2). (Br. 3, 6-7.) We are not persuaded. Ishikawa teaches a 24-hour waiting period between antibody injection and stem cell transplantation, and it is reasonable 5 Appellants argue that, if anything, Ishikawa "teaches away" from the claimed invention. (Br. 3.) Teaching away, however, is not relevant to an anticipation analysis. Celeritas Techs. Ltd. v. Rockwell Int'l Corp., 150 F .3d 1354, 1361 (Fed. Cir. 1998). 6 Appeal2013-008633 Application 12/447,634 for the Examiner to find that such a waiting period inherently falls within claims 1 and 2. This finding shifts the burden to Appellants to demonstrate, with evidence, that Ishikawa's 24-hour waiting period is not sufficient to allow substantial elimination of the ablating antibody from a patient's circulation or to clear the antibody from a patient's bloodstream such that its concentration is less than 10 ng/ml. See In re Best, 562 F.2d at 1254--55. Appellants have not done so: Although Appellants cite to data in the Specification showing that, for certain ACK2 preparations, 7 days is needed to clear all detectable ACK2 antibody from serum after injection (Br. 3), the claim does not require elimination of all detectable antibody, only substantial elimination or a concentration of less than 10 ng/ml. (FF6.) Conclusion of Law The evidence of record supports the Examiner's finding that Ishikawa anticipates claims 1 and 2. Claims 3-5, 13, 21, and 22 have not been argued separately and therefore fall with claims 1 and 2. 37 C.F.R. § 41.37(c)(l)(iv). II. Issue The Examiner has rejected claims 1-5, 13, 15, and 17-24 under 35 U.S.C. § 102(b) as anticipated by Down. (Ans. 3.) The Examiner finds that Down "teaches a method for stem cell engraftment, comprising contacting mammal with antibody that selectively binds to c-kit to selectively eliminate endogenous stem cells and introducing exogenous stem cell." (Final Act. 3.) The Examiner further finds that Down teaches the use 7 Appeal2013-008633 Application 12/447,634 of antibodies including ACK2 and that Appellants disclosed the use of ACK2 antibodies to practice the invention. (Id.) Appellants contend that Down teaches away from the claimed invention because Down "teaches the use of anti-c-kit antibodies ... selected ... to deplete cells via complement-mediated cell killing" rather than via interference with growth factor signaling as claimed. (Br. 5.) Appellants further contend that Down fails to teach a method in which exogenous stem cells are provided "after a period of time sufficient to substantially eliminate the anti-c-kit antibody from the patient circulation." (Id. at 5---6.) With respect to claims 2 and 3, Appellants argue that Down does not teach providing exogenous stem cells after a period of time such that "the antibody is present at a concentration of less than 10 ng/ml in the bloodstream." (Id. at 6-7.) The issue with respect to this rejection is whether the evidence of record support the Examiner's finding that Down anticipates claims 1 and 2. Findings of Fact FF7. Down discloses: [t]herapeutic compositions and methods for ... promoting acceptance of a graft . . . . The described methodology includes ... depleting and/or inactivating the hematopoietic stem cells of the recipient using ... at least one antibody specific for depleting and/or inactivating hematopoietic stem cells[;] preferably the antibody selectively depletes and/or inactivates primitive hematopoietic stem cells. The therapeutic composition preferably is administered prior to the administration of bone marrow, mobilized peripheral hematopoietic stem cells, or donor leucocytes. 8 Appeal2013-008633 Application 12/447,634 (Down Abstract; see also id. at 1:22-2:2, 5:19-27, 6:11-14, 7:4--16, 22:1- 11, 23:6-26, 24:9-16, 26:24--28, 27:10-18, 27:23-26, 28:1-11, 35:3-14, 38: 12-14, Example 2.) FF8. Down discloses that the donor and recipient of the graft may be mammals for purposes of its invention. (Id. at 7:4--16.) FF9. Down teaches that anti-c-kit antibodies can be specifically directed against hematopoietic cells in bone marrow and discloses an embodiment where an anti-c-kit antibody is the depleting/inactivating antibody. (Id. at 5:31---6:2, 69:2-8; see also id. at 26:3-7, 26:28-27:6.) FFlO. Down discloses ACK2 as an anti-c-kit antibody that prevents the binding of stem cell factor to the c-kit molecule. (Id. at Table 3.1.) FF 11. Down teaches a most preferred embodiment in which donor stem cells are administered after the depleting/inactivating antibody has been cleared from the circulatory system of the graft recipient. (Id. at 36:2-3.) FF12. Down teaches that, "[t]ypically, an anti-[hematopoietic stem cell] treatment agent, for example the administration of antibodies, will be given to the patient about 1, 2, 3, 4, or 5 days prior to stem cell transplantation depending up the rate of clearance of the agent from the recipient's circulation .... " (Id. at 38:31-39:2; see also id. at 39:26-28, 48:14--26.) Principles of Law "[D]isclosure of a broad genus does not necessarily specifically disclose a species within that genus." Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1377 (Fed. Cir. 2015). However, a disclosure that allows 9 Appeal2013-008633 Application 12/447,634 one skilled in the art to "at once envisage each member of [a] limited class" describes each member of the class "as if [the reference] had drawn each structural formula or had written each name." In re Petering, 301 F.2d 676, 681-82 (CCP A 1962). A specifically disclosed species may also anticipate even if it appears without special emphasis in a longer list. Perricone, 432 F.3d at 1376. Teaching away is not relevant to an anticipation analysis. Celeritas Techs. Ltd. v. Rockwell Int'l Corp., 150 F.3d 1354, 1361 (Fed. Cir. 1998). Analysis As discussed above, the methods of claims 1 and 2 require contacting a mammal with an anti-c-kit antibody that interferes with growth factor signaling and then introducing donor stem cells to the mammal once the antibody has been substantially eliminated from the mammal's circulation (claim 1) or is present at a concentration of less than 10 ng/ml (claim 2). Down teaches a method for promoting acceptance of a graft in a mammal, which comprises depleting and/or inactivating recipient hematopoietic stem cells by using an anti-c-kit antibody. (FF 7, FF8, FF9.) We find the disclosure of anti-c-kit antibody, a limited class, sufficient to disclose the subset of such antibodies that interferes with growth factor signaling. In re Petering, 301 F.2d at 681-82. Down also specifically identifies several anti-c-kit antibodies, including ACK2, that fall within this subset. (FF5, FFlO.) Finally, Down teaches a preferred embodiment in which donor stem cells are administered after the depleting/inactivating antibodies have been cleared from the recipient's circulatory system. 10 Appeal2013-008633 Application 12/447,634 (FFl 1.) Accordingly, we find that the evidence of record supports the Examiner's position that Down anticipates claims 1 and 2. Appellants contend that Down teaches depleting stem cells via complement-mediated cell killing rather than via interference with growth factor signaling as required by claim 1. (Br. 5.) Appellants cite as support portions of Down stating that "complement-mediated cell killing may be partially responsible for [] in vivo results" of stem cell depletion and that "inhibition of binding of the c-kit ligand is a not a prerequisite for [ anti-c- kit] antibodies to deplete hematopoietic stem cells." (Id (emphasis added).) Appellants further argue that Down teaches away from the claimed invention because it teaches that the more primitive stem cells were refractory to the depleting effects of ACK2 while 2B8, an anti-c-kit antibody that does not inhibit stem cell factor binding, had the most promising effect on preferentially depleting such stem cells. (Id.) We are not persuaded by Appellants' argument. The portions of Down cited by Appellants at most suggest that interference of growth factor signaling may not be the only or the most effective mechanism for stem cell depletion; they do not teach that anti-c-kit antibodies that interfere with such signaling are not useful in its method. See In re Fulton, 391F.3d1195, 1201 (Fed. Cir. 2004) ("The prior art's mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed."). In any event, teaching away is not relevant to an anticipation analysis. Celeritas Techs. Ltd., 150 F.3d at 1361. 11 Appeal2013-008633 Application 12/447,634 Appellants also contend that Down fails to teach the limitations in claims 1 and 2 regarding the relative timing of administering depleting antibodies and exogenous stem cells. (Id. at 5-7.) This argument is likewise unpersuasive. Down teaches that depleting antibodies are typically administered about 1-5 days prior to stem cell transplantation, and further teaches that donor stem cells most preferably are administered after such antibodies have been cleared from the recipient's circulatory system. (FF 11, FF12.) Thus, Down anticipates the limitation in claim 1 regarding substantial elimination of the antibody, and it is further reasonable for the Examiner to find that Down's waiting period of 1-5 days would inherently result in an antibody concentration of less than 10 ng/ml as set forth in claim 2. See In re Best, 562 F.2d at 1254--55. Neither have Appellants provided evidence sufficient to rebut the Examiner's position. Appellants argue that Down prefers ablative agents that are active for extended periods of time and thus "would almost certainly be providing stem cells in the window of time where there is active ablation of hematopoietic stem cells." (Br. 6.) Appellants base this argument on Down's statement that the depleting antibodies should preferably be capable of achieving certain results in an in vitro assay. (Id.) Appellants do not, however, provide any evidence correlating an antibody's effect in an in vitro assay with its rate of clearance in patient circulation. Conclusion of Law The evidence of record supports the Examiner's finding that Down anticipates claims 1 and 2. Claims 3-5, 13, 15, and 17-24 have not been 12 Appeal2013-008633 Application 12/447,634 argued separately and therefore fall with claims 1 and 2. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY We affirm the rejection of claims 1-5, 13, 21, and 22 under 35 U.S.C. § 102(b) as anticipated by Ishikawa. We also affirm the rejection of claims 1-5, 13, 15, and 17-24 under 35 U.S.C. § 102(b) as anticipated by Down. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 13 Copy with citationCopy as parenthetical citation