Ex Parte Wendel et alDownload PDFPatent Trial and Appeal BoardSep 15, 201610761237 (P.T.A.B. Sep. 15, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 101761,237 01122/2004 136 7590 09/19/2016 JACOBSON HOLMAN PLLC 400 Seventh Street N.W. Suite 700 Washington, DC 20004-2218 FIRST NAMED INVENTOR Albrecht Wendel 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. P61750US1 2027 EXAMINER HINES, JANA A ART UNIT PAPER NUMBER 1645 NOTIFICATION DATE DELIVERY MODE 09/19/2016 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): patent@jhip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ALBRECHT WENDEL and THOMAS HARTUNG 1 Appeal2013-010345 Application 10/7 61,23 7 Technology Center 1600 Before DONALD E. ADAMS, TA WEN CHANG, and RACHEL H. TOWNSEND, 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 testing blood for reaction to a substance, 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, one of the objectives of the invention is to assure "a smooth and reproducible procedure" when blood is used as a biological test system. (Spec. 3.) Further according to the Specification, 1 Appellants identify the Real Party in Interest as the inventors, Albrecht Wendel and Thomas Hartung. (Appeal Br. 3.) Appeal2013-010345 Application 10/7 61,23 7 this objective may be achieved by use of deep-frozen blood, which may be thawed before the material to be tested is brought into contact with the blood. (Id. at 3--4.) Claims 23-28 and 35--46 are on appeal. Claim 23 is illustrative and reads as follows: 23. A method of testing blood for reaction to a substance comprising the steps of: - selecting a cryopreserved unit dose comprising a blood product including viable white blood cells and a cryopreservative from among a plurality of identical cryopreserved unit doses obtained from a single or pooled sample of blood taken from a human or animal; thawing the cryopreserved unit dose; contacting the thawed, cryopreserved unit dose with the substance; and determining, by biological, physical, chemical, or physicochemical means, whether the viable white blood cells in the unit dose react with the substance in an immunofi.1nctional, toxic, or modulator'/ blood reaction. The claims stand rejected as follows: Claims 23, 24, 26, 27, and 35--46 are rejected under 35 U.S.C. § 102(b) as being anticipated by Lionetti. 2 Claims 23-28 and 35--46 are rejected under 35 U.S.C. § 102(b) as being anticipated by Boyse. 3 2 Lionetti et al., U.S. 4,004,975, issued Jan. 25, 1977. 3 Boyse et al., U.S. 5,192,553, issued Mar. 9, 1993. 2 Appeal2013-010345 Application 10/7 61,23 7 Issue l. The Examiner rejected claims 23, 24, 26, 27, and 35--46 under 35 U.S.C. § 102(b) as being anticipated by Lionetti. The Examiner finds that Lionetti discloses a method for "the freezing of granulocytes of peripheral blood and the production of a substantial yield of thawed viable cells as determined by in vitro characteristics."4 (Ans. 3.) Among other things, the Examiner finds that Lionetti discloses "the cryopreservation of concentrated [white blood cells] being frozen at -80Q C." (Id. at 5.) The Examiner finds that Lionetti teaches freezing the white cells "with a combination of HES, which functions as both a sedimenting and cryoprotective agent, and DMSO, a cryoprotective agent." (Id. at 4.) The Examiner finds that Lionetti teaches cryopreservation of concentrated white blood cells in the form of "2ml aliquots of leukocytes ... placed in plastic ... tubes" as well as in the form of "55ml bags containing cells."5 (Id. at 5.) The Examiner finds that Lionetti discloses thawing the white blood cells and analyzing them in various ways, including via a bacterial growth inhibition assay where the white blood cells are contacted with E. coli. (Id. at 5---6.) Appellants contend that Lionetti does not disclose "selecting a ... unit dose ... from among a plurality of identical cryopreserved unit doses .... " (Appeal Br. 12-14.) Appellants further contend that Lionetti fails to teach "the combined steps of [1] 'contacting the ... [leukocyte-containing] unit dose with the substance' and [2] 'determining ... whether ... an immunofunctional, 4 "[G]ranulocytes are white blood cells." (Ans. 3.) 5 Leukocytes are also white blood cells. (See generally Lionetti 2:67 ("Leukocytes, i.e. white cells").) 3 Appeal2013-010345 Application 10/7 61,23 7 toxic or modulatory blood reaction' occurs between 'leukocytes' and 'substance."' (Id. at 14 (alteration original).) Appellants do not separately argue the claims. Thus, we limit our discussion to claim 23 as representative. 6 The issue with respect to this rejection is whether the evidence of record supports the Examiner's finding that Lionetti disclose each element of claim 23. Findings of Fact FF 1. Lionetti relates to a "method of salvaging granulocytes, or white cells, from ... centrifuged whole blood" by freezing the white blood cells. (Lionetti Abstract, 1:6-10; see Ans. 3.) FF2. Lionetti teaches freezing the white blood cells through "a combination of hydroxyethyl starch (HES), which functions as both a sedimenting agent and a cryoprotective agent, and dimethylsulfoxide (DMSO), a cryoprotective agent." (Id. at Abstract, 2: 10-16; see generally Ans. 3--4.) FF3. Lionetti teaches a sedimentation procedure to isolate white blood cells where "[ s ]edimentation was undertaken ... using the same volume of cells, dilutions and [HES] concentrations" and where white blood 6 To the extent Appellants separately argued claim 41 in their Reply Brief (Reply Br. 8), that argument is untimely because Appellants did not separately argue claim 41 in the Appeal Brief. Ex parte Borden, 93 USPQ2d 1473 (BPAI 2010). In any event, Appellants state that claim 41 "essentially defines the same subject matter as (independent) claims 23 and 35." (Reply Br. 8.) Thus, there can be no dispute that claim 23 is representative of claim 41. 4 Appeal2013-010345 Application 10/7 61,23 7 cells are then cryopreserved in bags or in plastic tubes. (Id. at 4:38---68; see Ans. 5.) FF4. Lionetti teaches expressing white blood cell enriched supematants resulting from the sedimentation procedure, "about 50---60 ml," into small platelet preservation bags. (Id. at 4:38--49; see Ans. 5.) Lionetti teaches that these suspensions from the sedimentation procedure, "about 55 ml containing 6 x 108 white cells, were frozen by placing the bags flat in the freezer at-80Q C." (Id. at 4:58-61; see generally Ans. 5, 11, and 13.) FF5. Lionetti also teaches placing "[t]wo milliliter aliquots, approximately 2 x 107 cells, of leukocytes isolated by sedimentation ... in polyethylene plastic tubes ... and [freezing them] at 2Q C/min. to -80Q C." (Id. at 4:52-55; see generally Ans. 5.) FF6. Lionetti teaches that "[r]esidual HES remaining after sedimentation was the cryoprotective agent for half the units studied" while the remaining units also received 5% DMSO. (Id. at 4:47--49, 61---64; see generally Ans. 4--5.) FF7. Lionetti teaches thawing the tubes and plastic bags of frozen white blood cells. (Id. at 5: 1-7; see Ans. 5.) FF8. Lionetti teaches "a method of determining the feasibility of thawed cells by tests involving [the cells'] ability to inhibit growth of Escherichia (E.) coli," which serve as a means to describe the capacity of cryopreserved granulocytes to undergo the ingestion aspect of phagocytosis. (Id. at 2:24--28, 10:59---62; see generally Ans. 5-6.) FF9. In particular, Lionetti teaches that "[t]hawed granulocytes, 0.5 ml, isolated by the sedimentation procedure with HES[,] were diluted to 15.0 5 Appeal2013-010345 Application 10/7 61,23 7 ml with Normosol," further diluted, and added to proliferating E. coli. (Id. at 6:9-14; see Ans. 5.) FF 10. Lionetti teaches counting the bacteria in the mixture of white blood cells and E. coli and also teaches taking photographs of white blood cells removed from the mixture, which revealed ingested bacteria within the phagocytes (not shown). (Id. at 9:63---65; see Ans. 5-6.) FF 11. Lionetti teaches studies conducted with leukocytes sedimented with dextran or polyvinylpyrrolidone and then frozen with 10 and 15% DMSO in the presence or absence of glucose. (Id. at 10:63---66.) Lionetti teaches determining the phagocytic index for thawed cells diluted with plasma to 2% or 1 % DMSO. (Id. at 10:68-11 :9; see generally Ans. 6.) FF12. Lionetti provides data relating to trypan exclusion and myeloperoxidase activity for post-thawed leukocyte cryopreserved with either HES or HES and DMSO, where the cells were either washed or not washed after thawing. (Id. at Table 2, 8:58-9:41, 11: 13-24.) Analysis We find that the evidence of record supports the Examiner's finding that Lionetti anticipates claim 23. Lionetti teaches freezing white blood cells obtained from a sedimentation procedure in bags of about 55 ml containing 6 x 108 white cells as well as in two millimeter aliquots (FF4, FF5), which constitute "a plurality of identical cryopreserved unit doses obtained from a single or pooled sample of blood." (Appeal Br. 18 (Claims App'x).) Lionetti teaches thawing the aliquots of white blood cells. (FF7.) Lionetti teaches contacting the thawed cells with E. coli to determine 6 Appeal2013-010345 Application 10/7 61,23 7 whether the white cells inhibit E. coli growth (i.e., has an imnmnofunctional reaction to E. coli). (FF8-FF10.) Appellants argue that Lionetti does not disclose "a plurality of identical cryopreserved unit doses" because Lionetti discloses that white blood cell-enriched supematants from the sedimentation procedure, "about 50-60 ml," are expressed into small platelet preservation bags. (Appeal Br. 13.) Appellants thus contend that these frozen supematants cannot constitute identical unit doses because they contain variable amounts (i.e., between 50 and 60 ml) of white blood cells. (Id.) We are not persuaded. As the Examiner points out, Lionetti more specifically discloses that the suspensions from the sedimentation procedure are frozen in units of "about 5 5 ml containing 6 x 108 white cells." (Ans. 13-14; FF4.) Moreover, as the Examiner also points out, Lionetti further discloses cryopreserving white blood cells in two millimeter aliquots in polyethylene tubes. (Ans. 14; FF5.) Appellants contend that the two millimeter aliquots Lionetti discloses do not constitute identical units within the meaning of claim 23 because Lionetti Table 2 shows that there is a 50% standard deviation in the number of cells among the two millimeter aliquots. This argument is unpersuasive. "[I]n proceedings before the PTO, claims in an application are to be given their broadest reasonable interpretation consistent with the specification." In re Sneed, 710 F .2d 1544, 1548 (Fed. Cir. 1983). The Specification does not define "identical" unit dose; however, in discussing "unit doses" the Specification repeatedly refers to units of particular volume. (Spec. 9-10 ("The unit dose usually contains from 50 to 500 micro liters, preferably 100 micro liters, of whole blood, but it 7 Appeal2013-010345 Application 10/7 61,23 7 is not limited to those quantities. . . . The volume of whole blood that can be drawn at one time from a healthy human donor allows preparation of several thousand unit doses of, for example, 100 microliters.").) Thus, the broadest reasonable interpretation of the term "identical ... unit doses" encompasses doses that are identical in, e.g., source and volume, despite some variation in number of cells. Appellants further contend that Lionetti fails to teach "the combined steps of [1] 'contacting the ... [leukocyte-containing] unit dose with the substance' and [2] 'determining ... whether ... an immunofunctional, toxic or modulatory blood reaction' occurs between 'leukocytes' and 'substance."' (Appeal Br. 14 (alteration original).) We are not convinced. The Examiner has explained where and how these claim elements are disclosed in Lionetti (Final Act. 6-7; Ans. 5-7; see FF1-FF12), and Appellants fail to provide any evidence or argument in the Appeal Brief as to why the Examiner's articulation of the prima facie case with respect to these claim limitations are insufficient. In their Reply Brief, Appellants argue for the first time that Lionetti fails to teach "contacting the ... unit dose with the substance" and "determining [ ... ] whether the viable white blood cells in the unit dose react with the substance" because Lionetti "require that [white blood cells] be isolated from any cryopreservation media before the [white blood cells] are contacted with any substance for testing." (Reply 2-5.) Appellants have provided no explanation why this new argument could not have been presented in the Appeal Brief; accordingly, Appellants' new argument is untimely. Ex parte Borden, 93 USPQ2d 1473 (BPAI 2010). In any event, 8 Appeal2013-010345 Application 10/7 61,23 7 we are not persuaded by Appellants' argument. (FF2, FF6, FF9, FFl 1, FF12.) Finally, Appellants argue that "[a]ppealed claims provide, for the first time, the use of a blood product as a reagent in the testing of various substances for their suitability." (Reply Br. 8-9 (emphasis omitted).) In contrast, Appellants argue that Lionetti "describe the testing for safety and efficacy of a blood product, to be used in the treatment of humans, by contacting the blood product with a variety of reagent substances." (Id.) However, Appellants' argument in this regard does not point out any additional claim limitations that are not disclosed by Lionetti. Accordingly, we find that Lionetti anticipates claim 23. Claims 24, 26, 27, and 35--46 have not been argued separately and therefore fall with claim 23. II. Issue The Examiner rejected claims 23-28 and 35--46 under 35 U.S.C. § 102(b) as being anticipated by Boyse. The Examiner finds that Boyse discloses cryopreservation of neonatal or fetal hematopoietic stem and progenitor cells and the therapeutic use of such cells upon thawing. (Ans. 7.) The Examiner finds that Table III of Boyse shows samples of cord blood collected from infants. (Id. at 17-18.) The Examiner finds that these samples comprise "blood product[s] that [are] whole blood and includes viable ... white blood cells." (Id. at 9.) The Examiner finds that Boyse discloses layering 1 ml portions of cell suspensions created from cord blood 9 Appeal2013-010345 Application 10/7 61,23 7 stem and progenitor cells on top of cryoprotective medium in vials that are frozen and then subsequently thawed and analyzed. (Id. at 18.) The Examiner finds that Boyse discloses "creating a plurality of identical [unit doses]" by aliquoting cell suspension from a single sample into multiple tubes, bags and vials. (Id.) The Examiner further finds that Boyse discloses use of a cryoprotective agent such as DMSO. (Id. at 8.) The Examiner finds that Boyse discloses "thawed cells [being] tested by standard assays of viability (trypan blue exclusion) and ... microbial sterility, and tested to confirm and/or determine their identity relative to the patient, and for hematopoietic function." (Id. at 17.) For instance, the Examiner finds that Boyse discloses "numerous assays for hematopoietic stem or progenitor cells where various factors, alone or in combination[,] are tested for stimulation of colony formation upon inclusion in the blood culture mixture." (Id. at 9.) The Examiner finds that, "[t]herefore, [Boyse] disclose[s] determining whether the viable white blood cells in the unit dose reacts with a variety of stimulator substances in an immunofunctional, toxic, or modulatory blood reaction." (Id. at 17; see also id. at 8.) Appellants contend that Boyse does not disclose "'selecting ... from among ... identical ... [white-blood-cell containing] unit doses'" or "selecting a unit dose from a plurality of identical cryopreserved unit doses." (Appeal Br. 15, 16.) Appellants further contend that Boyse fails to teach "the combined steps of [ 1] 'contacting the ... unit dose with the substance' and [2] 'determining ... whether ... an immunofunctional, toxic or modulatory blood reaction' occurs between 'leukocytes' and 'substance."' (Id. at 16.) 10 Appeal2013-010345 Application 10/7 61,23 7 Appellants do not separately argue the claims. 7 Thus, we limit our discussion to claim 23 as representative. The issue with respect to this rejection is whether the evidence of record supports the Examiner's finding that Boyse disclose each element of claim 23. Findings of Fact FF 13. Boyse relates to "hematopoietic stem and progenitor cells of neonatal or fetal blood that are cryopreserved, and the therapeutic uses of such stem and progenitor cells upon thawing." (Boyse Abstract; see also id. at 8:43--46, 10:28-31; see generally Ans. 7.) FF 14. Boyse teaches that, "[i]n a preferred embodiment of the invention, the neonatal blood sample as thawed can be infused for hematopoietic reconstitution. Thus, it is envisioned that whole neonatal blood, cryopreserved and thawed, can be infused for therapy." (Id. at 24:64-- 68; see also id. at 18:59---62, 39:48-52; see generally Ans. 7.) FF15. Boyse teaches using cryoprotective agents, including DMSO, in cryopreserving cells. (Id. at 23: 1-2; see generally Ans. 8.) FF 16. Boyse teaches using "[ s ]ealed plastic vials ... or glass ampules can be used for multiple small amounts (1-2 ml), while larger volumes (100-200 ml) can be frozen in polyolefin bags .... " (Id. at 23:55---60; see Ans. 8.) FFl 7. Boyse teaches a protocol for cryopreserving viable hematopoietic stem and progenitor cells derived from human cord and placental blood comprising creating a cell suspension and then, "[i]n a 7 See supra note 6. 11 Appeal2013-010345 Application 10/7 61,23 7 cryovial containing 1 ml of a chilled, sterile cryoprotective medium of 20% DMSO/RPMI-1640, carefully layer[ing] a 1 ml portion of the ... cell suspension on top of the cryoprotective medium" before placing the vials in a freezing rack. (Id. at 43:49---68; see generally Ans. 16 and 18.) FF 18. Boyse teaches a service comprising collecting cord blood from an infant and allocating cells of each individual to "four cryules [i.e., standard freezing vials], two of which are assigned for storage to one freezer and two to another, independently-serviced, freezer." (Id. at 59:35---60:68; see generally Ans. 7-8 and 17-18.) FF 19. Boyse teaches that [t]he cryoprotective agent, if toxic in humans, should be removed prior to therapeutic use of the thawed neonatal stem and progenitor cells. In an embodiment employing DMSO as the cryopreservative, it is preferable to omit this step in order to avoid cell loss, since DMSO has no serious toxicity. . . . One way in which to remove the cryoprotective agent is by dilution to an insignificant concentration. (Id. at 25:12-21; see generally Ans. 8 and 18-19.) FF20. Boyse teaches that [i]n a preferred ... aspect of the invention, thawed cells are tested by standard assays of viability (e.g., trypan blue exclusion) and of microbial sterility ... , and tested to confirm and/or determine their identity relative to the patient, and for hematopoietic function. . . . Methods for identity testing which can be used include but are not limited to HLA (the major histocompatibility complex in man) typing ... , and DNA fingerprinting, which can be used to establish the genetic identity of the cells. (Id. at 25:50-26:64; see generally Ans. 8-9.) 12 Appeal2013-010345 Application 10/7 61,23 7 Analysis We find the preponderance of evidence supports the Examiner's finding that Boyse anticipates claim 23. Boyse discloses cryopreserving neonatal blood with a cryopreservative such as DMSO. (FF14, FF15.) Boyse discloses cryopreserving viable stem and progenitor cells derived from human cord and placental blood by combining 1 ml portions of a cell suspension with 1 ml of cryoprotective medium in cryovials for freezing. (FF 1 7; see also FF 18 (describing a service comprising collecting cord blood and allocating cells from each individual to four separate cryules ). ) Boyse describes thawing the cryopreserved neonatal blood and/or cells and testing them via different assays. (FF13, FF14, FF20). Appellants argue that Boyse does not suggest "'selecting ... from among .. .identical...[ white-blood-cell containing] unit doses,' as in the rejected claims," because "the multiple samples 'CB-1 ' -'CB-111 "' set forth in Table III of Boyse and cited by the Examiner "have different 'Total Volume[s]. "' (Appeal Br. 15-16 (alteration original).) We are not convinced. Boyse discloses, e.g., cryopreserving viable stem and progenitor cells derived from human cord and placental blood by combining 1 ml portions of a cell suspension with 1 ml of cryoprotective medium in cryovials for freezing. (Ans. 18; see also FF16-FF18.) In the Reply, Appellants do not appear to dispute that Boyse's cryovials constitute identical unit doses. Nevertheless, Appellants argue that Boyse does not anticipate claim 23 because Boyse isolates the blood cells from such cryovials prior to conducting assays and thus does not teach "contacting the [entire] thawed, cryopreserved unit dose [of WBCs and a cryopreservative] with the substance" and "determining ... whether the 13 Appeal2013-010345 Application 10/7 61,23 7 viable white blood cells in the unit dose react with the substance." (Reply Br. 7-8.) Appellants' argument is not persuasive. While Boyse does disclose a method that pellets thawed cells in the cryovials by centrifugation and subsequently separating the cells from the supernatant, Boyse also teaches that, in preferred embodiments, cryopreservative should not be removed, in order to avoid cell loss. (FFl 9; see also Boyse 51:35--40 (Ficoll-Hypaque cell separation and DMSO removal are two steps that are omitted in a preferred embodiment of the invention).) Finally, we note but do not find persuasive Appellants' statements in the Appeal Brief that Boyse does not anticipate the claims because "the ... claim limitation to selecting a unit dose from a plurality of identical cryopreserved unit doses 'negates anticipation"' and "the combined steps of [ 1] 'contacting the ... [leukocyte-containing] unit dose with the substance' and [2] 'determining ... whether ... an immunofunctional, toxic or modulatory blood reaction' occurs between 'leukocytes' and 'substance"' fails to "'identically appear' in the reference disclosure." (Appeal Br. 16-17 (alteration original).) The Examiner has explained where and how these claim elements are disclosed in Boyse (Final Act. 7-10), and Appellants fail to articulate with any specificity why the prima facie case with respect to these claim limitations are insufficient. Claims 24--28 and 35--46 have not been argued separately and, therefore, fall with claim 23. 14 Appeal2013-010345 Application 10/7 61,23 7 SUMMARY We affirm the rejection of claims 23, 24, 26, 27, and 35--46 as anticipated by Lionetti. We further affirm the rejection of claims 23-28 and 35--46 as anticipated by Boyse. 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 15 Copy with citationCopy as parenthetical citation