Ex Parte Burton et alDownload PDFPatent Trial and Appeal BoardMar 24, 201713567226 (P.T.A.B. Mar. 24, 2017) Copy Citation 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. CMMI218US2 6936 EXAMINER RAWLINGS, STEPHEN L ART UNIT PAPER NUMBER 1643 MAIL DATE DELIVERY MODE 13/567,226 08/06/2012 63322 7590 03/27/2017 IMMUNOMEDICS, INC. 300 AMERICAN ROAD MORRIS PLAINS, NJ 07950 Jack D. Burton 03/27/2017 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 PATENT TRIAL AND APPEAL BOARD Ex parte JACK D. BURTON, RHONA STEIN and DAVID M. GOLDENBERG Appeal 2014-008841 Application 13/567,226 Technology Center 1600 Before DEBORAH KATZ, ULRIKE W. JENKS, and JOHN G. NEW, Administrative Patent Judges. KATZ, Administrative Patent Judge. DECISION ON APPEAL Appellants1 seek our review, under 35 U.S.C. § 134(a), of the Examiner’s decision to reject claims 1, 2, 4, and 8—20.2 (App. Br.3 2.) We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 The real party in interest are said to be Immunomedics, Inc. and the Center for Molecular Medicine and Immunology. (App. Br. 1.) 2 Claims 1—2, 4, and 8—20 are currently pending in this application, following cancelation of claims 3 and 5—7. (App. Br. 2.) 3 Except as otherwise noted, citations to the Appeal Brief refer to the brief filed May 6, 2014. Appeal 2014-008841 Application 13/567,226 Appellants identify the following related appeals: Application 13/528,077 (Appeal No. 2014-002239); Application 13/483,761 (Appeal No. 2014-002802); and Application 12/869,823 (Appeal No. 2014-008773). (Supplemental App. Br. 2.) Introduction Appellants’ Specification is directed to methods of therapeutic treatment of cancer and other diseases involving CD74 positive cells. Specifically, Appellants provide a method of using interferon-y (“IFN-y”) to increase expression of the antigen CD74 on the surface of cancer cells. These cells are then treated with anti-CD74 antibodies to cause growth inhibition and apoptosis. (Spec. 13.) Appellants’ claim 1 recites: 1. A method of killing a cell that is resistant to anti- CD74 antibody comprising a) . exposing the anti-CD74 resistant cell to interferon-y; b) increasing expression of CD74 on the cell surface by exposing the cell to interferon-y; and c) exposing the cell to an anti-CD74 antibody or antigen-binding fragment thereof after the cell has been exposed to interferon-y, wherein exposing the cell that is resistant to anti-CD74 antibody to interferon-y results in an increase in the percent growth inhibition or percent apoptosis of the cell exposed to anti- CD74 antibody that is two fold higher or more. (App. Br. 13; Appendix A.) 2 Appeal 2014-008841 Application 13/567,226 The Examiner entered several rejections, including: claims 1, 2, 4, and 8—20 as being indefinite under 35U.S.C. § 112, second paragraph; claims 1, 2, 4, and 8—13 and 15—20 as failing to comply with the written description requirement under 35 U.S.C. §112, first paragraph; claims 1, 2, 4, and 8—20 as failing to comply with the enablement requirement under 35 U.S.C. § 112, first paragraph; claims 1, 2, ,4 and 8—20 as being anticipated by Hansen 14 under 35 U.S.C. § 102(b); and claims 1, 2, and 4 as being rendered obvious by Hansen 1 and Hansen 25 under 35 U.S.C. §103. Appellants indicate that for the purpose of appeal, claim 1 is representative of all the claims on appeal. (App. Br. 4.) Appellants do not argue separately for the patentability of any of the other claims. Accordingly, we focus on claim 1 in our analysis. See 37 C.F.R. § 41.37(c)(iv). 35 U.S.C. § 112, second paragraph — Indefiniteness Under 35 U.S.C. § 112, second paragraph, Appellants’ claims must particularly point out and distinctly claim the subject matter the applicant regards as his invention. The statutory language of particularity and distinctness indicates that claims must be cast in clear and not vague or ambiguous, terms. If, instead, “a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to 4U.S. Patent No. 7,312,318 B2, issued December 25, 2007. 5U.S. Patent No. 7,951,921 B2, issued May 31, 2011. 3 Appeal 2014-008841 Application 13/567,226 more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite.” Ex parte Miyazaki, 89 USPQ2d 1207, 1211 (BP AI 2008) (precedential). The Examiner rejected all of Appellants’ claims, finding it is not clear to what extent cells must be resistant to an anti-CD74 antibody to be regarded as “resistant” within the claimed scope. (Ans. 3 and 17—18.) The Examiner points to Figure 3 of Appellants’ Specification, which is reproduced below. FIG, 3 Figure 3 depicts the anti-proliferative effect of anti-CD-74 antibody milatuzumab in (A) GDM-1 and (B) Kasumi-1 AML cell lines with or without IFN-y, as determined by MTT assay. (Spec., ^ 28.) Figure 3 shows that GDM-1 and Kasumi-1 cells are growth inhibited by the anti-CD74 antibody to some extent without IFN-y, although growth inhibition increases with IFN-y treatment. Specifically, Figure 3 shows that GCM-1 cells are inhibited 20% and Kasumi-1 cells are inhibited 5% with 4 Appeal 2014-008841 Application 13/567,226 anti-CD74 antibody alone. (See Ans. 3, n.2.) Similar results are shown in Figure 4 for the induction of apoptosis in GDM-1 and Kasumi-1 cells when treated with anti-CD74 antibodies alone. (See Spec., 129, Fig. 4.) Though Appellants argue that these are examples of “resistant” cells (see App. Br. 7— 8), Figure 3 indicates cells may be sensitive to anti-CD74 antibody to some extent without defining how much sensitivity is encompassed by Appellants’ claim term “anti-CD74 resistant cell.” Appellants argue that the Examiner incorrectly rejected the current claims as indefinite because the claims provide the functional characteristics of being resistant to anti-CD74 antibody and having increased expression of CD74 on the cell surface after being exposed to IFN-y. (App. Br. 5.) We agree with the Examiner that this is not a persuasive argument because it does not provide any way for one of ordinary skill in the art to know what cells fall within the scope of Appellants’ claims before they practice the recited method. (See Ans. 23—24.) Patent claims should be sufficiently definite to inform the public of the bounds of the protected invention, i.e., what subject matter is covered by the exclusive rights of the patent, so that competitors can avoid infringement. To require a person of ordinary skill to actually practice the recited steps to determine whether they are infringing those steps is counter to the notice function of a claim. Appellants also argue that the reference in their Specification to Stein6 clarifies the meaning of the term “resistant” in their claims. (App. Br. 5—6, citing Spec., 17.) Stein reportedly shows that exposure to the anti-CD74 antibody milatuzumab increased proliferation in GDM-1, Kasumi-1 and 6 Stein etal., 115 Blood 5180-90 (2010). 5 Appeal 2014-008841 Application 13/567,226 Kasumi-3 cells 113%. (Stein, Table 2.) Appellants compare this result to the results reported for other cell lines (e.g., MCL, ALL, CLL), which reportedly demonstrate less than 100% proliferation when exposed to milatuzumab, indicating inhibition and sensitivity to the antibody. We are not persuaded by Appellants’ argument because even if some cells can be characterized as “resistant,” it is not clear what standard should be used to determine if other cells are “resistant” as claimed. Similarly, we consider Appellants’ argument that a cell line that is resistant to an anti-CD74 antibody is one that “shows little to no growth inhibition induced by the antibody, while a sensitive cell line is one that shows a substantial inhibition of cell proliferation in the presence of an antibody” to be unpersuasive. (App. Br. 6.) This explanation also fails to provide a clear standard for making a determination of what is encompassed by “resistant” cell. Appellants argue further that one of ordinary skill in the art would have known from the plain language of the Specification that a cell resistant to anti-CD74 antibodies as claimed is one that shows increased expression of CD74 on the cell surface when exposed to IFN-y. (App. Br. 5.) In contrast, Appellants’ Specification states that “cytotoxicity does not always correlate with antigen expression in the malignant B-cells lines examined.” (Spec., 1130; see Ans. 25.) Additionally, as noted by the Examiner, Stein provides data showing inconsistencies between the expression of several cell surface antigens and sensitivity to antibodies directed to them. (Ans. at 5, n.5; at 9, n.8; and at 28—29, n.23; citing Stein at 5182, Table 2.) Because this evidence contradicts Appellants’ argument, we do not find it to be persuasive. 6 Appeal 2014-008841 Application 13/567,226 Appellants also argue that the use of the term “resistant” in regard to the response to anti-HLA-DR antibody by AML cells supports the use of the term “resistant” in Appellants’ claims. (App. Br. 6.) We are not persuaded because neither use of the term provides a standard for determining which cells are “resistant.” Appellants fail to persuade us that the Examiner erred in finding Appellants ’ claims amenable to two or more plausible claim constructions, where it is not clear to what extent cells can be affected by anti-CD74 antibody alone and still be considered to be “resistant.” Appellants have declined to more precisely define the metes and bounds of the claimed invention by amendment, as suggested by the Examiner. (See Ans. 22—23.) Accordingly, Appellants fail to persuade us that the Examiner erred in rejecting the claims under 35 U.S.C. § 112, second paragraph, as being indefinite. 35 U.S.C. § 112, first paragraph — Written Description The critical inquiry for determining whether there is a sufficient written description “is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad Pharm., Inc., v. Eli Lilly & Co., 598 F3d 1336, 1351 (Fed. Cir. 2010). “[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials.” Id. at 1350. 7 Appeal 2014-008841 Application 13/567,226 The Examiner rejected Appellants’ claims for failing to satisfy the written description requirement of 35 U.S.C. § 112, finding that it is not clear what an “anti-CD74 resistant cell” is. (Ans. 5.) The Examiner finds that, at best, Appellants’ Specification provides a description of enhancing sensitivity of AML cells to the cytotoxic effects of the specific anti-CD74 antibody milatuzumab or the mouse antibody LL1 in the presence of IFN-y. (Ans. 6.) The Examiner finds that Appellants’ Specification does not describe performing the claimed method on any resistant cell with any anti- CD74 antibody. (Id.) Appellants point to paragraph 130 and Figure 3 of their Specification, arguing that it describes the AML cell lines Kasumi-3 and GDM-1 as examples of antibody resistant cell lines. (App. Br. 7; Reply Br. 4.) Appellants also argue that by citing Stein, paragraph 7 of their Specification provides a written description of the claimed anti-CD74 resistant cells. (App. Br. 7.) We are not persuaded that the disclosure of two, or even three, specific cell lines in Appellants’ Specification or in Stein is a sufficient written description of the genus of cells that fall within the scope of Appellants’ claims. Similarly, we are not persuaded that the disclosure of one anti-CD74 antibody, milatuzumab, is a sufficient written description of the full scope of the genus of antibodies that fall within the scope of Appellants’ claims. (See Ans. 29.) Appellants do not direct us to evidence that one of skill in the art would know that any other cells are resistant to anti-CD74 antibodies or that other antibodies would increase growth inhibition or percent apoptosis in such cells. Although Appellants argue that Figure 3 of their Specification provides a reason for one of skill in the art to have believed that any “resistant” cell and any anti-CD74 antibody would 8 Appeal 2014-008841 Application 13/567,226 produce the results claimed (App. Br. 7—8), Figure 3 provides data for only two AML cell lines, while the Specification explains that cytotoxicity does not always correlate with antigen expression in malignant B-cells. (See Spec., 1130.) As noted by the Examiner, Appellants’ Specification discloses that only two out of three of the AML cell lines tested demonstrated an IFN-y increased milatuzumab-mediated growth inhibition — indicating that one third of the cells lines tested did not show the claimed effect. (Ans. 29, citing Spec., 1117: “IFN-y induced intracellular CD74 in all 3 lines (from 85%—868%) (see, e.g., FIG. 2A-2B). In 2/3 lines, IFN-y increased milatuzumab-mediated growth inhibition (23.7 to 44.8% and -3.9 to 30.9%, respectively) (FIG. 3, FIG. 4) .”). Because Appellants’ Specification shows that not all cells fall within the scope of Appellants’ claims, we agree with the Examiner that Appellants’ Specification does not demonstrate possession of the genus of resistant cells claimed. In addition, the Examiner cites to Stancovski7 and Pettersen8 as evidence that merely binding to an antigen does not indicate an antibody will inhibit cell growth. These references show that while some antibodies inhibit tumor cell growth or induce apoptosis, other antibodies directed to the same antigen do not. (Ans. 33—34, citing Stancovski at abstract and Pettersen, abstract.) Thus, because Appellants’ Specification describes only one antibody, we agree with the Examiner that the Specification does not demonstrate possession of the genus of anti-CD74 antibodies claimed. 7 Stancovski et al., 88 Proc. Nat’1 Acad. Sci. USA 8691 (1991). 8 Pettersen et al., 162 J. Immunol. 7031 (1999). 9 Appeal 2014-008841 Application 13/567,226 Appellants are correct that they need not demonstrate efficacy for every species within their claimed genus (see App. Br. 9), but “[a]n applicant cannot under 35 U.S.C. § 112 claim a broader invention than that set forth in the written description contained in his specification.” In re Sus, 306 F.2d494, 505 (C.C.P.A. 1962). Appellants’ Specification provides data for only two different cell lines and one antibody, while also indicating the method may not work with other cell lines. Therefore, Appellants argument is not persuasive. Appellants also argue that the Examiner inappropriately defined the term “resistant” as showing no effect whatsoever of an anti-CD74 antibody on cell proliferation or apoptosis. (See App. Br. 8.) Even if, as Appellants argue, they were acting as their own lexicographer in providing a definition of “resistant,” Appellants’ argument fails to persuade us. Appellants do not direct us to any portion of their Specification that provides a specific meaning of the term “resistant” that would indicate possession of the entire genus. We decline to incorporate a limitation from Appellants’ Specification that is not expressly provided for in the claims. See In re Prater, 415 F.2d 1393, 1395 (CCPA 1969) (‘“reading a claim in the light of the specification,’ to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the into a claim, ’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.”). Appellants fail to persuade us that the Examiner erred in rejecting the claims under 35 U.S.C. § 112, first paragraph, for lack of written description support. 10 Appeal 2014-008841 Application 13/567,226 35 U.S.C. § 112, first paragraph — Enablement The scope of the claims must not be broader than the scope of the enabling description in the specification. “The scope of enablement, in turn, is that which is disclosed in the specification plus the scope of what would be known to one of ordinary skill in the art without undue experimentation.” Natl Recovery Tech., Inc. v. Magnetic Separation Systems, Inc., 166 F.3d 1190, 1196 (Fed. Cir. 1999). To determine whether undue experimentation would have been required to carry out claimed subject matter, we look to factors provided in n re Wands, 858 F.2d 731, 736—37 (Fed. Cir. 1988), including “(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.” The Examiner rejected Appellants’ claims as failing the enablement requirement of 35 U.S.C. § 112 because the Specification does not indicate how one of skill in the art would determine which cells are “resistant” to an anti-CD74 antibody as recited in the claims. (Ans. 8; Ans. 50.) The Examiner finds that the scope of Appellants’ claims is broad, not being limited to the AML cell lines exemplified in the Specification. (Ans. 8; Ans. 53) The Examiner also finds that Stein, the prior art cited by Appellants, demonstrates that the correlation between antigen expression on a cell and sensitivity to anti-proliferative effects of an antibody was unpredictable. (Ans. 8—9; Ans. 50.) The Examiner finds further that because it was known that not all antibodies that bind a tumor antigen would have the same cytotoxic effects, it could not have been presumed that all anti-CD74 11 Appeal 2014-008841 Application 13/567,226 antibodies would be effective in Appellants’ claimed method. (Ans. 9-10; Ans. 51—52.) In light of these findings, the Examiner determines that Appellants’ Specification would only enable Appellants’ claimed method for GDM-1 and Kasumi-1 AML cell and the antibody milatuzumab described in the Specification. (Ans. 10.) Appellants argue that a person of ordinary skill in the art could have practiced the claimed method without undue experimentation because the Specification provides the functional characteristics of the cells encompassed by the claims as well as detailed procedures for assaying anti- CD74 antibodies to determine which cells would have the functional characteristics required. (App. Br. 9-10.) We are not persuaded by Appellants’ arguments because for the reasons discussed above, the Specification does not identity a standard by which “resistant” cells could be determined to be within the scope of Appellants’ claims. We are also persuaded by the evidence cited by the Examiner that it would have been unpredictable to determine which cells and antibodies would fall within any range of resistance. Appellants fail to persuade us that the Examiner erred in rejecting the claims under 35U.S.C. § 112, first paragraph, for lack of an enabling disclosure. 35 U.S.C. § 102 - Anticipation The Examiner rejected Appellants’ claims as being anticipated by Hansen 1 under 35 U.S.C. § 102(b). (Ans. 11—13.) Hansen teaches a method of treating a malignancy, including leukemias and lymphomas, etc., recited in Appellants’ claim 4, by administering an anti-CD74 antibody 12 Appeal 2014-008841 Application 13/567,226 before, during, or after treatment with another therapeutic agent, including IFN-y. (Hansen 1, 25:41—66 and 27:36—52.) Appellants argue that Hansen 1 does not teach or suggest exposing a cell that is “resistant” to anti-CD74 antibody to IFN-y and does not teach or suggest that the IFN-y would result in an increase in the growth inhibition or percent apoptosis. (App. Br. 10-11.) The Examiner acknowledges that Hansen 1 does not expressly teach a cell that has the functional elements recited in Appellants’ claims, but finds that because the Specification does not specifically identify the attributes of such cells, absent a showing to the contrary, the cells taught in Hansen 1 are the same as those within the scope of Appellants’ claims. The Examiner finds that because Hansen 1 and Appellants’ claims recite types of cells that overlap (e.g. lymphomas, leukemias, etc.). Hansen 1 would inherently have the same functional characteristics as those claimed if the steps of Appellants’ claimed method were applied to some of them. (Ans. 57—58; see Hansen 1, at 26:3—10.) We agree with the Examiner. Hansen 1 teaches the same steps as claimed: exposing a cell to IFN-y and exposing the cell to an anti-CD74 antibody. Although it is not clear to what standard the cells of Hansen 1 should be compared, we have no reason to believe that the broad categories of cells taught by Hansen 1, which overlap with the broad categories of cells encompassed by Appellants’ claims, would not include cells resistant to anti- CD74 antibodies. 13 Appeal 2014-008841 Application 13/567,226 35 U.S.C. § 103 - Obviousness The Examiner rejected claims 1, 2, and 4 as being obvious over Hansen 1 and Hansen 2. (Ans. 13—15.) The teachings of Hansen 1 are described above. The Examiner cited Hansen 2 for its teaching that AML cells express CD74, which is considered to be a target epitope on these cells. {Id., see Hansen 2 at 8:51—66.) The Examiner finds that one of ordinary skill in the art would have been motivated to treat patients with AML using the method of Hansen 1 because Hansen 2 teaches these cells express CD74. (Ans. 15.) Appellants argue that not all AML cells are resistant to anti-CD74, so the recitation of AML cells in Hansen 2 is not necessarily a teaching of cells resistant to anti-CD74. (App. Br. 12.) Lor the reasons discussed above in regard to the rejection under 35 U.S.C. § 102 and inherent disclosure of “resistant” cells, we are not persuaded by this argument. Conclusion Upon consideration of the record and for the reasons given, the rejection of claims 1, 2, 4, and 8—20 as being indefinite under 35 U.S.C. § 112, second paragraph is sustained; the rejection of claims 1, 2, 4, and 8—13 and 15—20 as failing to comply with the written description requirement under 35 U.S.C. § 112, first paragraph is sustained; the rejection of claims 1, 2, 4, and 8—20 as failing to comply with the enablement requirement under 35 U.S.C. § 112, first paragraph is sustained; the rejection of claims 1, 2, 4, and 8—20 as being anticipated by Hansen 1 under 35 U.S.C. § 102(b) is sustained; and 14 Appeal 2014-008841 Application 13/567,226 the rejection of claims 1, 2, and 4 as being rendered obvious by Hansen 1 and Hansen 2 under 35 U.S.C. §103 is sustained. Therefore, we affirm the decision of the Examiner. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136. AFFIRMED 15 Copy with citationCopy as parenthetical citation