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Patent Trials and Appeals Board

Mar 2, 2022

2021002981 (P.T.A.B. Mar. 2, 2022)

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. 15/299,085 10/20/2016 Anup Sood 818254 5098 95683 7590 03/02/2022 Leydig, Voit & Mayer, Ltd. (Frankfurt office) Two Prudential Plaza, Suite 4900 180 North Stetson Avenue Chicago, IL 60601-6731 EXAMINER YAKOVLEVA, GALINA M ART UNIT PAPER NUMBER 1641 NOTIFICATION DATE DELIVERY MODE 03/02/2022 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): chgpatent@leydig.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte ANUP SOOD, ARUNKUMAR NATARAJAN, DMITRY DYLOV, LAKSHMI SIREESHA KAANUMALLE, and ELIZABETH MARY MCDONOUGH Appeal 2021-002981 Application 15/299,085 Technology Center 1600 ____________ Before DONALD E. ADAMS, JOHN E. SCHNEIDER, and RACHEL H. TOWNSEND, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 1, 3-9, 11-26, and 33-41 (Appeal Br. 2). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as “Danaher Corporation” (Appellant’s November 20, 2020, Appeal Brief (Appeal Br.) 2). Appeal 2021-002981 Application 15/299,085 2 STATEMENT OF THE CASE Appellant’s disclosure “relates generally to methods and systems for reducing inherent autofluorescence of biological materials in images of those biological materials and in particular to reduction of autofluorescence by photobleaching” (Spec. ¶ 1). Claims 1, 5, and 15 are reproduced below: 1. A method for reduction of autofluorescence in biological samples, the method comprising: providing one or more biological microscopy samples comprising tissue material; contacting the one or more biological microscopy samples with a solution comprising a triplet sensitizer; and irradiating the one or more biological microscopy samples with visible light having a light intensity, wherein at least 50% of the light intensity emanates from a wavelength interval within the visible range, and wherein the wavelength interval has a width of up to 80 nm, wherein the triplet sensitizer and the wavelength interval reduces autofluorescence exhibited by the one or more biological microscopy samples relative to autofluorescence exhibited by the sample in the absence of the triplet sensitizer or in response to a wideband irradiation wavelength interval having a width of greater than 80 nm. (Appeal Br. 14.) 5. The method of claim 1, wherein the light intensity within a range of 5 mW/cm2 to 300 mW/cm2. (Id. at 15.) 15. The method of claim 1, wherein the wavelength interval is 470 nm to 550 nm. (Id. at 16.) Appeal 2021-002981 Application 15/299,085 3 Grounds of rejection before this Panel for review: I. Claims 1, 3-9, 11-26, and 33-41 stand rejected under 35 U.S.C. § 103 as unpatentable over the combination of Sood ’3922 and Wilkes.3 II. Claims 1, 3-9, 11-26, and 33-41 stand rejected under 35 U.S.C. § 103 as unpatentable over the combination of Davis,4 Sood ’392, and Wilkes. III. Claims 1, 3-9, 11-26, and 33-41 stand rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-30 of Sood ’032 in view of Wilkes. Rejection I: ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Sood discloses “[h]uman breast tissue array samples . . . obtained as tissue slides embedded in paraffin . . . [and] H&E stained” (Sood ¶ 111; see also id. ¶ 2 (Sood discloses that “hematoxylin and eosin staining (H&E) is one of the most common staining methods in histology.”); Ans. 5). 2 Sood et al., US 2013/0178392 A1, published July 11, 2013, now US 9,176,032 (“Sood ’032), issued Nov. 3, 2015. 3 Wilkes et al., US 2013/0137119 A1, published May 30, 2013. 4 Davis et al., Characterizing and Diminishing Autofluorescence in formalin- fixed Paraffin-embedded Human Respiratory Tissue, 62 J. HISTOCHEM & CYTOCHEM 405-23 (2014). Appeal 2021-002981 Application 15/299,085 4 FF 2. Sood discloses the “irreversible quenching of residual eosin fluorescence by photo-induced electron transfer based chemistry, . . . referred to a Photoinduced Chemical Bleaching (PICB),” which involves excitation of eosin in the presence of an electron donor or acceptor. Following excitation an electron is transferred between the dye and either the donor or the acceptor and the resultant reactive dye undergoes further reaction or rearrangements with an accompanied change in optical properties. For example, a biological sample is stained with eosin. After imaging, the slide is flooded with a borate salt buffer and light from mercury, halogen or xenon lamp, an LED or another light source is shined on the tissue to bleach the eosin signal. After signal bleaching, the biological sample is available for further molecular analysis either by IHC, IF or FISH. (Sood ¶ 62 (emphasis added); see also id. at Abstract (emphasis added) (Sood discloses a method comprising “the steps of providing a hematoxylin and eosin stained biological sample containing multiple targets, observing the sample, removing the hematoxylin and partially removing the eosin by washing the sample, contacting the sample with a borate salt, and irradiating the sample to remove the residual eosin fluorescence.”); Sood ¶ 118 (Sood exemplifies a method wherein H&E stained slides comprising human breast tissue array samples, were subsequently treated with “dicyclopentyl diphenylborate . . . and irradiated with 500 nm light for 30 minutes”); Ans. 5-6). FF 3. Examiner finds that Sood does not disclose riboflavin, Appellant’s elected species of triplet sensitizer (Ans. 6). FF 4. Wilkes discloses a method, wherein a sample is contacted “with a photo-sensitizer . . . [and exposed] to light under conditions sufficient for the Appeal 2021-002981 Application 15/299,085 5 photo-sensitizer to photobleach contaminating non-bacterial particulates present in the sample” (Wilkes, Abstract; see also Ans. 6). FF 5. Wilkes discloses “[e]xemplary photo-sensitizing agents,” such as “phloxine B” and “riboflavin” (Wilkes ¶ 84). FF 6. Wilkes discloses that “samples can be exposed to visible light, such as a visible spectrum from 380 nm to 750 nm, such as 570 nm to 590 nm” (Wilkes ¶ 86; see also Ans. 7). FF 7. Wilkes discloses exposing sample “to a light intensity of . . . 1,000 to 50,000 LUX . . . or 1,000 to 50,000 lumens” (Wilkes ¶ 86; see also Ans. 7). FF 8. Wilkes discloses that the combination of a photo-sensitizer and light radiation produces “singlet oxygen in a manner that can be controlled as to intensity and duration,” wherein the singlet oxygen “reacts with the conjugated π orbitals in autofluorescent compounds” (Wilkes ¶¶ 80, 86; see also Ans. 7). FF 9. Wilkes discloses that its method may be controlled by: (a) the amount of sensitizer added to the sample . . ., (b) the wavelength and intensity of the incident light (e.g., visible spectrum from 380 nm to 750 nm), (c) the identity of the sensitizer and its corresponding maximum absorbance frequency (e.g., for phloxine B its absorption maximum is about 570-590 nm), and (d) exposure duration (e.g., 1 minute to 30 minutes). (Wilkes ¶ 80; see also Ans. 6-7.) ANALYSIS Based on the combination of Sood ’392 and Wilkes, Examiner concludes that, before the effective filing date of Appellant’s claimed invention, it would have been prima facie obvious to substitute Wilkes’ riboflavin-based photo-sensitizing method for the borate salt-based Appeal 2021-002981 Application 15/299,085 6 methodology utilized in Sood’s method of photo-bleaching a tissue sample (see Ans. 8; see also FF 1-9). Claim 1: Appellant’s claim 1 is reproduced above. The method of Appellant’s claim 1 requires, inter alia, “one or more biological microscopy samples comprising tissue material” (Appeal Br. 14 (emphasis added)). A sample comprising tissue material does not exclude tissue that was previously stained, such as the H&E stained tissue disclosed by Sood, which is a biological sample, within the scope of Appellant’s claimed invention, that will exhibit autofluorescence (see FF 1-2). We further find no requirement in Appellant’s claim 1 that limits the scope of the phrase “autofluorescence in biological samples” to “inherent autofluorescence,” “tissue autofluorescence,” or “endogenous autofluorescence” as asserted by Appellant (see Appeal Br. 5-6). Sjolund v. Musland, 847 F.2d 1573, 1581 (Fed. Cir. 1988) (“[W]hile it is true that claims are to be interpreted in light of the specification and with a view to ascertaining the invention, it does not follow that limitations from the specification may be read into the claims.”). Therefore, we are not persuaded by Appellant’s contentions regarding the scope of claim 1 or that “Examiner improperly relies on residual dye fluorescence (fluorescence not arising from the tissue itself) as allegedly being autofluorescence,” within the scope of Appellant’s claimed invention (Appeal Br. 5-6; see also id. at 6-9; Reply Br.5 3-4; cf. Ans. 11-12 5 Appellant’s March 29, 2021, Reply Brief. Appeal 2021-002981 Application 15/299,085 7 (Examiner finds Appellant’s contentions relating to the interpretation of the term autofluorescence “is not supported by the instant disclosure and is not commensurate in scope with the instant claims, which are drawn to methods for reduction of autofluorescence in biological samples.”). See In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997). [A]ppellants urge us to consult the specification and some of the cited prior art . . . and interpret the disputed language more narrowly in view thereof. When read in light of this material, according to applicants, the “true” meaning of the phrase emerges. We decline to attempt to harmonize the applicants’ interpretation with the application and prior art. Such an approach puts the burden in the wrong place. It is the applicants’ burden to precisely define the invention, not the PTO’s. See 35 U.S.C. § 112, ¶ 2. . . . [T]his section puts the burden of precise claim drafting squarely on the applicant. Id. For the foregoing reasons, we are not persuaded by Appellant’s contention that “Sood’s fluoresence is distinct from autofluorescence,” within the scope of Appellant’s claimed invention (Appeal Br. 8). For the same reasons, we are not persuaded by Appellant’s contention that “Examiner errs by relying on an unreasonably broad interpretation of the subject matter recited by Appellant’s claims” (Reply Br. 3). As discussed above, based on the combination of Sood and Wilkes, Examiner concludes that it would have been prima facie obvious to substitute Wilkes’ riboflavin-based photo-sensitizing method for the borate salt-based methodology utilized in Sood’s method of photo-bleaching a tissue sample (see Ans. 8; see also FF 1-9). Wilkes discloses that the combination of a photo-sensitizer and light radiation produces “singlet oxygen in a manner that can be controlled as to intensity and duration,” Appeal 2021-002981 Application 15/299,085 8 wherein the singlet oxygen “reacts with the conjugated π orbitals in autofluorescent compounds” (FF 8). We find no evidence on this record to support a finding that those of ordinary skill in this art would not have reasonably expected Wilkes’ methodology to quench fluorescence of a stained tissue sample, such as that disclosed by Sood. Therefore, we are not persuaded by Appellant’s contention that “Sood and Wilkes are not analogous art to the claimed subject matter, and are not available in a rejection under 35 U.S.C. § 103” (see Appeal Br. 9; see also id. at 8 (“Wilkes, describes reduction in signals from contaminating non-bacterial particulates (Wilkes, Abstract) rather than describing reduction in autofluorescence. Contaminants are external to the tissue, and thus the signals of Wilkes cannot be reasonably characterized as arising from autofluorescence”); Reply Br. 4-5). For the foregoing reasons, we are not persuaded by Appellant’s contentions regarding inherency (Appeal Br. 8-9; see also Reply Br. 4-5; cf. Ans. 16 (Examiner explains that in view of the interpretation of the term “autofluorescence” discussed above, the combination of Sood and Wilkes makes obvious Appellant’s claimed invention). Claims 5 and 15: Appellant’s claims 5 and 15 are reproduced above. Examiner “examin[ed] these claims on the assumption that they read on the elected species . . . riboflavin as a triplet sensitizer,” “[o]therwise, these claims would be deemed withdrawn from consideration” as drawn to a non-elected invention (Ans. 7; see also Examiner’s June 21, 2018, Appeal 2021-002981 Application 15/299,085 9 Requirement for Restriction and Election of Species; Appellant’s August 20, 2018, Response to Requirement for Restriction/Election). As Wilkes explains, its method may be controlled by, inter alia, “the wavelength and intensity of the incident light (e.g., visible spectrum from 380 nm to 750 nm)” and “the identity of the sensitizer and its corresponding maximum absorbance frequency (e.g., for phloxine B its absorption maximum is about 570-590 nm)” (FF 9; see also FF 8). Stated differently, Wilkes discloses that both wavelength and light intensity may be used to control its method, wherein the wavelength of light is chosen to correspond to the absorption maximum of the triplet sensitizer, which on this record, is riboflavin. Thus, we agree with Examiner’s rationale that the wavelength of light is “implied and/or inherent to the use of riboflavin as a photosensitizer” (Ans. 8; cf. Appeal Br. 10 (Appellant contends that “merely that riboflavin or another triplet sensitizer absorbs light at a certain wavelength range does not inherently or otherwise mean that the wavelength of the light source/irradiation has to exactly (inherently or inseparably) match that of riboflavin” and that “the light intensity recited by Claim 5 and other claims is neither inherently nor inseparably bound to the property or characteristics of riboflavin”)). In addition, because Wilkes discloses that light intensity is a factor that may be used to control its method, we find that it would have been prima facie obvious to optimize the light intensity within the range disclosed by Wilkes, which absent evidence on this record, includes the range required by Appellant’s claimed invention (see FF 7-9). For the foregoing reasons, we are not persuaded by Appellant’s contentions that “Examiner overlooks that the parameters recited by [claims] Appeal 2021-002981 Application 15/299,085 10 5, 15, 16, 24, and 35 are those of the irradiation or the light source, which are independent from the properties of the triplet sensitizer” (Appeal Br. 10). For the same reasons, we are not persuaded by Appellant’s contentions regarding inherence (id.; see also Reply Br. 5). CONCLUSION The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness. Rejection I: The rejection of claims 1 and 5 under 35 U.S.C. § 103 as unpatentable over the combination of Sood ’392 and Wilkes is affirmed. Claims 3, 4, 6-9, 11-14, 17-23, 25, 26, 33-35, and 36-41 are not separately argued and fall with claim 1. Claims 16, 24, and 35 are not separately argued and fall with claims 5 and 15. Rejection II: We vacate Rejection II as cumulative to Rejection I. Obviousness-type Double Patenting: ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness-type double patenting? ANALYSIS Sood ’032’s claim 1 is reproduced below: 1. A sequential method of preparing a hematoxylin and eosin stained biological sample for analysis comprising: (a) providing a hematoxylin and eosin stained biological sample containing multiple targets; (b) observing the hematoxylin and eosin . . . [signal] from the stained biological sample; Appeal 2021-002981 Application 15/299,085 11 (c) removing the hematoxylin and partially removing the eosin by washing the sample; (d) contacting the sample with an electron transfer reagent where the electron transfer reagent is a borate salt represented by the following structural formula: wherein: each R1, R2, and R3 is, independently, an alkyl, an alkenyl, an alkynyl, an aryl or a heteroaryl, wherein said alkyl, alkenyl, alkynyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylamino, amino, hydroxyl, cyano, halogen, or nitro, R4 is an alkyl, an alkenyl, or an alkynyl, wherein said alkyl, alkenyl, or alkynyl is optionally substituted with one or more substituents selected from the group consisting of (C1-C4)alkyl, aryl, (C1-C4)alkoxy, (C1- C4)alkylamino, amino, hydroxyl, cyano, halogen, or nitro, and M+ is selected from the group consisting of organic and inorganic cations; (e) irradiating the sample of step (d) to remove residual fluorescence. (Sood ’032 21:56-22:26; see generally Ans. 10.) Examiner relies on Wilkes as discussed above (see FF 4-9; see generally Ans. 10). Appeal 2021-002981 Application 15/299,085 12 Based on the combination of Sood ’032 in view of Wilkes, Examiner concludes that, before the effective filing date of Appellant’s claimed invention, it would have been prima facie obvious to substitute Wilkes riboflavin-based photo-sensitizing method for the borate salt-based methodology utilized in Sood ’032’s method of photo-bleaching a tissue sample (see Ans. 10). The rationale supporting this conclusion is substantially the same as that set forth in the obviousness rejection discussed above. For the reasons set forth above, we are not persuaded by Appellant’s contentions regarding “residual fluorescence” or that Appellants asserted “deficiencies of Wilkes discussed with reference to 35 USC § 103 undermine the rejection” (Appeal Br. 12; see also Reply Br. 6-7). CONCLUSION The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness-type double patenting. The rejection of claim 1 under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-30 of Sood ’032 in view of Wilkes is affirmed. Claims 3-9, 11-26, and 33-41 are not separately argued and fall with claim 1. Appeal 2021-002981 Application 15/299,085 13 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 3-9, 11-26, 33-41 103 Sood ’392, Wilkes 1, 3-9, 11-26, 33-41 1, 3-9, 11-26, 33-41 103 Davis, Sood ’392, Wilkes6 1, 3-9, 11-26, 33-41 Sood ’032, Wilkes 1, 3-9, 11-26, 33-41 Overall Outcome 1, 3-9, 11-26, 33-41 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED 6 For the reasons discussed above this rejection is vacated.