Ex Parte Calatzis et alDownload PDFPatent Trials and Appeals BoardJun 10, 201912522364 - (D) (P.T.A.B. Jun. 10, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/522,364 03/10/2010 46002 7590 06/12/2019 JOYCE VON NATZMER A GRIS & VON NA TZMER LLP 43 West 43rd Street, Suite 104 New York, NY 10036-7424 FIRST NAMED INVENTOR Andreas Calatzis 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. 3024-160 9177 EXAMINER TSAY,MARSHAM ART UNIT PAPER NUMBER 1656 NOTIFICATION DATE DELIVERY MODE 06/12/2019 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): uspto-mail@NATZMER-LAW.COM eofficeaction@appcoll.com 46002 © avn-law .com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ANDREAS CALATZIS, MARTIN GLAUNER, AXEL SCHUBERT, and MAX KESSLER Appeal2018-006559 Application 12/522,364 Technology Center 1600 Before DEMETRA J. MILLS, ERIC B. GRIMES, and DAVID COTTA, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a). The Examiner has rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm. Appeal2018-006559 Application 12/522,364 STATEMENT OF CASE The pending claims are directed to a container for use in serum testing, and a method of using that container for serum testing. Claims 16, 21. The glass vial used in the serum testing may be coated with a surface covering. Spec. 1 7. In this embodiment possible coagulation activation in the test liquid by the glass surface is excluded, while the superior sealing properties of the glass material when compared to plastic material are still used. The similar effect of suppressing possible coagulation activation in the test liquid by the glass surface can be realized by covering the glass surface ( or at least the inner portion of the glass surface) with a layer of one or more substances that are not able to activate coagulation if they are in contact with blood or blood components. Spec. 17. The following claims are representative. 16. A container, comprising an undivided cup, wherein the undivided cup comprises a co-lyophilized composition comprising following constituents: (i) at least one activator of coagulation; (ii) a calcium salt in an amount of 1-lOOµmol/ml, sufficient to ensure recalcification of the test liquid; (iii) a stabilizer; (iv) optionally one or more inhibitors and coagulation factors or activated coagulation factors, wherein the co-lyophilized composition comprises 10% or less by weight of a liquid, and wherein the container (a) has a form that reduces its inner lateral profile from a top opening of the container to a closed bottom of the container and (b) is made out of (i) glass and a plastic insert (ii) glass having a surface covering, wherein the surface covering is a layer of one or more substances that are not able to activate coagulation if they are in contact with blood or blood components. 2 Appeal2018-006559 Application 12/522,364 21. A method of performing a viscoelastic analysis on a test liquid, comprising: a.) providing a container which has a form that reduces its inner lateral profile from a top opening of the container to a closed bottom of the container and is made out of (i) glass and plastic, wherein the container is designed so that coagulation activation in the test liquid by any glass surface of the container is excluded or (ii) glass having a surface covering, wherein the surface covering is a layer of one or more substances that are not able to activate coagulation if they are in contact with blood or blood components, wherein the container comprises a diagnostic co-lyophilized composition comprising following constituents: (i) at least one activator of coagulation; (ii) a calcium salt in an amount of 1-1 OOµmol/ml, sufficient to ensure recalcification of the test liquid; (iii) a stabilizer; (iv) optionally one or more inhibitors and coagulation factors or activated coagulation factors, wherein the co-lyophilized composition comprises 10% or less by weight of a liquid and is present in an amount sufficient for performing one single viscoelastic analysis of the test liquid; b.) directly adding a test liquid into said container, wherein the diagnostic colyophilized composition contained therein is dissolved in said test liquid to provide a mixture; c.) optionally, transferring the mixture into an apparatus suitable for performing a viscolelastic analysis; or putting the container into an apparatus suitable for performing a viscolelastic analysis; and d.) performing the viscoelastic analysis of said mixture. Cited References Bums us 4,529,614 3 July 16, 1985 Appeal2018-006559 Application 12/522,364 Zuckerman US 5,223,227 June 29, 1993 Baugh '712 US 5,972,712 Oct. 26, 1999 Brucato et al. US 6,100,072 Aug. 8, 2000 Cohen et al. US 6,537,819 B2 Mar. 25, 2003 Baugh '563 WO 98/49563 Nov. 5, 1998 Benecky WO 02/079375 Al Oct. 10, 2002 (Corresponding to US 2003064414) Sigma Aldrich Catalog, T786, T782 (2001 ). BD Vacutainer® Tube Guide (2005). Grounds of Rejection 1 1. Claims 16-17 and 19--20 are rejected under pre-AIA 35 U.S.C. §I03(a) as being unpatentable over Brucato in view ofBenecky,[2] Sigma and Bums. 2. Claims 2--4, 6, 11, 15, 21-28, 33, 35-37, 39--40, and 46 are rejected under pre-AIA 35 U.S.C. § I03(a) as being unpatentable over Brucato in view of Benecky, Sigma, Bums, Zuckerman, and Cohen. 3. Claim 9 is rejected under pre-AIA 35 U.S.C. § I03(a) as being unpatentable over Brucato in view of Benecky, Sigma, Bums, Zuckerman, Cohen and Baugh '712. 1 The Examiner has stated that "Claim(s) 2-11, 15-17, 19--28, 33, 35--40, 46 (partially) is/are rejected." Non-final Action mailed April 5, 2017, page 1. However, none of the rejection in the Non-final Action or in the Answer includes any of claims 5, 7, 8, 10, or 3 8. 2 The Examiner indicates that Benecky, US 2003064414, corresponds to WO 02079375, and the Examiner appears to refer to paragraph numbers in US 2003064414 in the Answer. 4 Appeal2018-006559 Application 12/522,364 FINDINGS OF FACT The Examiner's findings of fact are set forth in the Answer at pages 3-24. The following facts are highlighted. 1. Brucato disclose a reagent based on recombinant tissue factor (TF) with defined phospholipids and other stabilizers, where the reagent is in a liquid or lyophilized formulation, and is useful for determining at least fibrinogen levels, percent coagulation factor activity, prothrombin time (PT), percent PT activity, and PT ratio, in a patient sample using clinical coagulation instruments ( col. 2 lines 22-30, col. 2, line 65 to col. 3, line 5). At col. 10, lines 12--40, Brucato disclose a lyophilized TF reagent composition comprising recombinant TF, calcium chloride 10 mM, dextran 5%, glycine 5%, albumin 0.3%. 2. Brucato's TF reagents have many applications (see FFl), where the reagent activates the extrinsic pathway of coagulation ( col. 7 lines 18- 23, col. 7-8). 3. Brucato et al. disclose preparing the lyophilized TF reagent composition and further combining said lyophilized TF reagent composition and stabilizers with a blood sample to measure PT/fibrinogen levels/clot formation (col. 10, lines 13-29, col. 10, lines 55---65, col. 14, lines 13-20, col. 12 lines, 58---67). 4. Brucato et al. disclose that the TF formulation comprising phospholipids, other stabilizers including buffers, and calcium chloride salt, can be in a single vial reagent, where the TF reagent is in lyophilized form (col. 3, lines 6-33, col. 7, lines 12-14). 5. Benecky et al. provide methods to rapidly assess the overall coagulant properties of blood and blood products by inhibiting the intrinsic 5 Appeal2018-006559 Application 12/522,364 contact pathway in vitro and stimulating activation of the extrinsic activation pathway with at least one procoagulant agent. The method enables the measurement of blood coagulation via the extrinsic pathway, which is more representative of the in vivo state of coagulation (abstract, p. 5). 6. Benecky discloses that the intrinsic pathway can be inhibited by contacting the whole blood or blood product sample with a surface having low thrombogenic activity; examples of surfaces having low thrombogenic activity include plastic, glass, siliconized glass; [3] the contact can be performed during collection, storage, or handling of the whole blood or blood product sample. The whole blood sample may be collected in the presence of an anticoagulant, the anticoagulant will block the extrinsic or common pathways. Benecky, p. 16. The effect of the anticoagulant in the blood sample must be reversed at the time blood coagulability or clotting time is measured. This is accomplished by the addition of calcium salt. Benecky p. 16; Ans. 4- 5. 7. Benecky discloses a composition comprising recombinant TF, calcium salt, and albumin, further comprises a low molecular weight heparin (LMWH) (an optional inhibitor), to assess coagulation of a blood sample. Benecky, p. 20. 3 The definition of "siliconized ": treated or coated with a silicone // siliconized glassware. https://www.merriam-webster.com/ dictionary/ siliconized 6 Appeal2018-006559 Application 12/522,364 8. Benecky discloses that any number of available procedures for measuring blood clotting may be used. Instruments suitable for this purpose include for example, all instruments that measure mechanical impedance caused by initiation of a clot, the reagents that initiate clotting or affect clotting times may be presented in various forms, including but not limited to solutions, lyophilized or air-dried forms. Benecky, p. 17. The containers or vessels, including test tubes, comprising the at least one procoagulant (i.e. TF) are used with instruments to measure the clotting time and/or viscoelastic properties of a blood sample, including a thromboelastograph device (Benecky, p. 5, p. 6-9 working examples). 9. Benecky discloses test kits for determining coagulability, comprising collection tubes having low thrombogenic activity that contain at least one procoagulant of the extrinsic pathway, where the vessel further comprises an inhibitor of coagulation, and calcium salt to reverse the effect of the inhibitor ([0035], [0036], [0037], [0062]). 10. Sigma discloses glass vials/containers having a form that reduces its inner lateral profile from a top opening of the container to a closed bottom of the container for use in collecting or storing biological samples/fluids were readily available (Sigma catalog 2001: pages T782, T786). The glass V-vials are graduated, comprise plastic tops for storage and/or have plastic-faced polymeric tops. 11. Bums discloses methods for coating substrates such as plastics and glass to impart anticoagulant and hydrophobic properties to the substrate, and to substrates so coated. The method is particularly useful in coating the internal surfaces of blood test vessels for 7 Appeal2018-006559 Application 12/522,364 receiving blood samples for subsequent testing. The method imparts the desired properties to the vessel in a single step by combining silicone containing material and anticoagulant with a water vehicle, followed by air drying (at least abstract, col. 1-3). 12. Zuckerman discloses a cup that can be used for blood coagulation tests in instruments, such as a thromboelastograph instrument ( col. 1- 2) and Cohen et al. disclose a method and apparatus for measuring blood clotting characteristics that uses the cup of Zuckerman ( col. 1- 2, also detailed description). 13. Zuckerman discloses that the inner surface of the cup tapers outward quickly near the top. The profile of the cup appears to reduce from the opening to the bottom (col. 3 lines 11-20, Fig. 2). 14. Baugh discloses a composition that is equivalent to Brucato and Benecky, in regards to the components that it comprises, and that this composition can also be used in a method to determine and/or measure clotting time in a blood sample ( col. 9 lines 17-25, col. 19 lines 47-67). Baugh discloses that heparinase can be included in the composition as a heparin inhibitor (col. 20 lines 1-2). 15. The Specification states that, "The diagnostic composition or reaction mixture of the present invention comprises constituents, which are per se known in the art." Spec. 11. PRINCIPLES OF LAW In making our determination, we apply the preponderance of the evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F .2d 1422, 1427 8 Appeal2018-006559 Application 12/522,364 (Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings before the Office). "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). Claim Interpretation Claim 16 includes the following language: Wherein the container ... (b) is made out of (i) glass and a plastic insert (ii) glass having a surface covering, wherein the surface covering is a layer of one or more substances that are not able to activate coagulation if they are in contact with blood or blood components. We interpret the above language to mean that subnumerals (i) and (ii) of claim 16 are alternatives which should have been connected by the term "or" as in claim 21. This interpretation is consistent with the Specification, page 16, which states that, "the container 1 might be designed by combination of two materials, e.g., glass and plastic or glass and a surface covering." "[D]uring examination proceedings, claims are given their broadest reasonable interpretation consistent with the specification." In re Hyatt, 211 F.3d 1367, 1372 (Fed. Cir. 2000). Obviousness The Examiner concludes, based on the factual evidence above, that: It would have been obvious to one of ordinary skill in the art ... to combine the references and incorporate the lyophilized TF reagent composition of Brucato et al. into glass vials ... , including a glass vial having a form that reduces its inner lateral profile from a top opening of the container to a closed bottom 9 Appeal2018-006559 Application 12/522,364 of the container, where the inner surface of said glass vial is coated with a material that does not activate coagulation, i.e. a silicone containing material, because it was known in the art that siliconized glass vials can be used to contain the compositions and/or samples disclosed by Brucato et al. ... The motivation to do so is given by the prior art. Brucato et al. disclose single vial reagents comprising a lyophilized TF composition comprising stabilizers, calcium chloride 10 mM, where the reagent activates the extrinsic pathway of coagulation. It is disclosed that the containers used to contain the TF formulation should preferably have a surface having low thrombogenic activity, such as plastic, glass, siliconized glass, including collection tubes, which would generally be known to have tapered bottoms (Benecky et al.). Glass V-vials [Sigma, T786] having plastic-faced polymeric tops were readily available at the time of the invention and coating glass vials to inhibit incidental clotting of collected blood samples was also known. Ans. 6-7; emphasis added. Appellants contend that Bums suggests that his surface forms an anticoagulant/- organopolysiloxane prepolymer matrix that is mechanically fixed to the substrate of interest. Thus, with the addition of blood, the mechanical coating dissolves in the blood to the extent necessary to impart anticoagulant properties to the sample, while the organopolysiloxane provides sufficient flow for the blood to impart hydrophobicity to the surface of the substrate of interest ( col. 1, lines 53---60). While Sigma suggests tapered vials, the Examiner has not provided any argumentation why the person skilled in the art would select such a tapered vial for Brucato' s reagent. Appellant further notes that the primary reference, Brucato, discloses liquid and lyophilized reagents for determining prothrombin time for determining deficiencies in the coagulation system (Brucato' s Abstract and Field of the Invention). Appellant submits that the person skilled in the art 10 Appeal2018-006559 Application 12/522,364 would not consider modifying a testing vial in which Brucato' s reagents are used to measure prothrombin time to include an inner surface covering that is thought to release anticoagulant into the sample, as such an anticoagulant could compromise the prothrombin time determination. App. Br. 10-11. Appellants further argue that, "in Brucato there is no dissolving of the co-lyophilized composition in said test liquid, but a dissolving of the co-lyophilized composition in the buffer followed by the addition of the test liquid." App. Br. 12. ANALYSIS Appellants do not provide separate argument for dependent claims with respect to rejection 1. We select claim 16 as representative claim for purposes of this rejection. We agree with the Examiner's fact finding, statement of the rejection and responses to Appellants' arguments as set forth in the Answer. We find that the Examiner has provided evidence to support a prima facie case of obviousness. We provide the following additional comment to the Examiner's argument set forth in the Non-Final Rejection (mailed April 5, 2017) and Answer. The cited references support the Examiner's prima facie case of obviousness. Brucato teaches a lyophilized composition having the same components as the co-lyophilized composition recited in the claim. In particular, Brucato discloses preparing a lyophilized TF reagent composition and combining the lyophilized TF reagent composition and stabilizers with a blood sample to measure PT/fibrinogen levels/clot formation (PT; prothrombin time) (col. 10 lines 28-34, lines 55---65, col. 14 11 Appeal2018-006559 Application 12/522,364 lines 13-20). Brucato further discloses that the lyophilized TF reagent composition can be in a single vial reagent (col. 7 lines 12-14); therefore, Brucato reasonably discloses a container comprising a lyophilized TF reagent composition comprising TF, calcium chloride 10 mM, dextran 5%, glycine 5%, albumin 0.3%. Ans. 5. We have interpreted claims 16 and 21, to alternatively require that the recited container be made of either (i) glass and a plastic insert or (ii) glass having a surface covering. Thus, in order to meet the claims, the Examiner need only establish one of the two alternative container conformations. Benecky teaches that it was well known at the time of the invention in the blood parameter measurement art to use "a surface having low thrombogenic activity." Benecky, p. 16. Benecky further discloses: Examples of surfaces having low thrombogenic activity include plastic, glass, and siliconized glass. The contact can be performed during collection, storage, or handling of the whole blood or blood product sample. By the term "low thrombogenic activity" as used herein is meant having little or no blood clotting activity. Preferably, the surface having low thrombogenic activity will inhibit the whole blood or blood product sample clotting time from between about 10 to about 3600 seconds longer than a suitable control, more preferably from about 50 to about 1500 seconds, and even more preferably, from about 150 to about 1050 seconds longer than the control. Benecky, p. 16; italicized emphasis added. The Examiner concludes that It would have been obvious to one of ordinary skill in the art at the time that the invention was made to combine the references and incorporate the lyophilized TF reagent composition of Brucato et al. into glass vials known and available in the art at the time of the invention, including a glass vial having a form 12 Appeal2018-006559 Application 12/522,364 that reduces its inner lateral profile from a top opening of the container to a closed bottom of the container, where the inner surface of said glass vial is coated with a material that does not activate coagulation, i.e. a silicone containing material, because it was known in the art that siliconized glass vials can be used to contain the compositions and/or samples disclosed by Brucato et al. (instant claim 16). The motivation to do so is given by the prior art. Brucato et al. disclose single vial reagents comprising a lyophilized TF composition comprising stabilizers, calcium chloride 10 mM, where the reagent activates the extrinsic pathway of coagulation. It is disclosed that the containers used to contain the TF formulation should preferably have a surface having low thrombogenic activity, such as plastic, glass, siliconized glass, including collection tubes, which would generally be known to have tapered bottoms (Benecky et al.). Ans. 9. We agree with the Examiner's stated prima facie case of obviousness. Appellants argue that the person skilled in the art would not consider modifying a testing vial in which Brucato' s reagents are used to measure prothrombin time to include an inner surface covering, such as that of Bums, that releases anticoagulant into the sample, as such an anticoagulant could compromise the prothrombin time determination. We are not persuaded by Appellants' argument. The claim 16(b) limitation alternative of a "(ii) glass having a surface covering" form of a serum vial is known from the combination of Benecky and Sigma. Therefore, Bums is not required to meet the limitations of claim 16(b )(i). In particular, at the time of the invention, glass vials/containers with plastic tops, having a form that reduces its inner lateral profile from a top opening of the container to a closed bottom of the container for use in collecting 13 Appeal2018-006559 Application 12/522,364 biological samples/fluids were readily available (Sigma catalog 2001, pp. T782, T786). It was also known in the art that it was desirable for serum containers to have surfaces with low thrombogenic activity. Benecky, p. 16; Ans. 5. According to Benecky, low thrombogenic surfaces, include glass, plastic and siliconized glass. Benecky, p. 16. It would have been obvious to one of ordinary skill in the art to select a serum vial with an insert having a reduced inner lateral profile as taught by the V-tubes of Sigma. It would have been further obvious to select from the low thrombogenic tube surfaces, as suggested by Benecky, including siliconized glass for the surface of the V-vial of Sigma (Sigma, T 786). It would have been obvious to place the Brucato lyophilized composition, which corresponds to the composition recited in the claims, in a serum test vial for serum testing. FF 1, 4. Put another way, Benecky discloses that siliconized glass has low thrombogenic activity, and Benecky suggests the use of siliconized glass for the assessment of whole blood. Abstract. Siliconized glass includes glass coated with silicone. See, footnote 3 above. Bums also discloses that it was well known in the art to treat or coat serum vessels with silicone containing material and anticoagulant. Bums, col. 1, 11. 40-50. Appellants do not provided evidence ( attorney argument is not evidence), that the presence of an anticoagulant on the surface of the vial that is intended to prevent random coagulation - not to change the properties of the substance - would materially affect the function of Brucato' s co-lyophilized composition. We agree with the Examiner that It would have been obvious to one of ordinary skill in the art ... to combine the references and incorporate the lyophilized TF reagent 14 Appeal2018-006559 Application 12/522,364 composition of Brucato et al. into glass vials ... , including a glass vial having a form that reduces its inner lateral profile from a top opening of the container to a closed bottom of the container, where the inner surface of said glass vial is coated with a material that does not activate coagulation, i.e. a silicone containing material, because it was known in the art that siliconized glass vials can be used to contain the compositions and/or samples disclosed by Brucato. Ans. 7. Appellants also argue that, "in Brucato there is no dissolving of the co-lyophilized composition in said test liquid, but a dissolving of the co- lyophilized composition in the buffer followed by the addition of the test liquid." App. Br. 12. We agree with the Examiner that Brucato discloses that the lyophilized formulation may be in a single vial reagent ( col. 7 lines, 12-14); therefore, it would be obvious that a test sample, such as blood, can be added directly to a vial containing the lyophilized TF reagent and dissolve the lyophilized composition. Ans. 22. Appellants rely on their arguments presented for rejection 1 to challenge obviousness rejections 2 and 3. We are not persuaded for the reasons set forth above. App. Br. 11. Any remaining arguments of Appellants have been addressed by the Examiner in the Answer, and we adopt the Examiner's responses as our own. Obviousness rejections 1-3 are affirmed for the reasons of record. 15 Appeal2018-006559 Application 12/522,364 CONCLUSION OF LAW The cited references support the Examiner's obviousness rejections 1- 3, which are affirmed for the reasons of record. All pending, rejected claims fall. AFFIRMED 16 Copy with citationCopy as parenthetical citation