DIGNITY HEALTHDownload PDFPatent Trials and Appeals BoardMar 1, 20212020003932 (P.T.A.B. Mar. 1, 2021) 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. 15/031,141 04/21/2016 Stephen L. Macknik 128464.00183 2670 26710 7590 03/01/2021 QUARLES & BRADY LLP ATTN: IP DOCKET 411 E. WISCONSIN AVENUE SUITE 2350 MILWAUKEE, WI 53202-4428 EXAMINER PERREIRA, MELISSA JEAN ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 03/01/2021 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): pat-dept@quarles.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte STEPHEN L. MACKNIK, SUSANA MARTINEZ-CONDE, and HECTOR RIEIRO ____________ Appeal 2020-003932 Application 15/031,141 Technology Center 1600 ____________ Before DONALD E. ADAMS, ERIC B. GRIMES, and JAMIE T. WISZ, Administrative Patent Judges. WISZ, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 seeks review of claims 1, 4–10, 13–16, and 21–24. We have jurisdiction under 35 U.S.C. § 6(b). For the reasons set forth below, we REVERSE. 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 Dignity Health. Appeal Br. 2. Appeal 2020-003932 Application 15/031,141 2 CLAIMED SUBJECT MATTER The Specification describes the recognition that “pericyte information, generated in vivo, may be used in identifying and/or treating a subject condition, such as a neural degeneration condition elicited by epilepsy, as well as other conditions.” Spec. ¶ 7. Pericytes are described as “perivascular cells that wrap around endothelial cells of capillaries and venules throughout the body, and are responsible for multiple physiological functions.” Id. at ¶ 26. The Specification further describes methods and kits for producing pericyte information “using intravenous administration of an effective amount of a solution including fluorescent markers that can selectively label pericytes.” Id. at ¶ 8. Claims 1, 10, and 21, reproduced below, are the independent claims: 1. A method for identifying a subject condition, the method comprising: administering intravenously to a subject an effective amount of an injectable solution comprising fluorescent conjugated Dextran markers, having a molecular weight in a range between 3 kiloDaltons and 70 kiloDaltons, to selectively label pericytes throughout the subject’s body; acquiring, using an imaging system, fluorescence signals originating from labeled pericytes to produce pericyte information associated with tissues of the subject’s body; and generating a report identifying a subject condition using the pericyte information. 10. A method for treating a subject condition, the method comprising: Appeal 2020-003932 Application 15/031,141 3 administering intravenously to a subject an effective amount of an injectable solution comprising fluorescent conjugated Dextran markers, having a molecular weight in a range between 3 kiloDaltons and 70 kiloDaltons, to selectively label pericytes throughout the subject’s body; acquiring, using an imaging system, fluorescence signals originating from labeled pericytes to produce pericyte information associated with tissues of the subject’s body; identifying a subject condition using the pericyte information; and adapting a treatment using the identified subject condition. 21. A method for staining pericytes in a subject, the method comprising steps of: providing an effective amount of an injectable solution comprising fluorescently conjugated dextran, the fluorescently conjugated dextran having a molecular weight in a range between 3 kiloDaltons and 70 kiloDaltons and being capable of selectively labeling pericytes throughout the subject; and administering intravenously to the subject the effective amount of the injectable solution such that the fluorescently conjugated dextran selectively binds to pericytes in the subject. Appeal Br. 26–28 (Claims Appendix). REJECTIONS The Examiner rejected claims 1, 4–10, 13–16, and 21–24 under 35 U.S.C. § 101 as being directed to patent-ineligible subject matter. Appeal 2020-003932 Application 15/031,141 4 The Examiner rejected claims 1, 5 and 7 under 35 U.S.C. § 103(a) as obvious over Hirase.2 The Examiner rejected claims 1, 4–10, 13–16, and 21–23 under 35 U.S.C. § 103(a) as obvious over Choi3 in view of Guerin,4 Caruso,5 and Hirase and further in view of Richardson,6 Bell,7 and Comeau.8 ISSUES AND ANALYSIS Rejection of claims 1, 4–10, 13–16, and 21–24 under 35 U.S.C. § 101 as being directed to patent-ineligible subject matter. The Examiner finds that claims 1, 4–10, 13–16, and 21–24 are directed to a judicial exception without significantly more. Final Act. 3. Specifically, the Examiner finds that the “claimed invention is directed to the administration of a fluorescent marker to a subject to image pericytes 2 Hirase et al., Two-Photon Imaging of Brain Pericytes In Vivo Using Dextran-Conjugated Dyes, GLIA, 46, 95–100 (2004) (“Hirase”). 3 Choi et al., WO 2012/099448 A2, published July 26, 2012 (“Choi”). 4 Guerin et al., The Dynamics of Blood-Brain Barrier Breakdown in an Experimental Model of Glial Cell Degeneration, Neuroscience, Vol. 103, No. 4, 873–883 (2001) (“Guerin”). 5 Caruso, et al. Ultrastructural Descriptions of Pericyte/Endothelium Peg- socket Interdigitations in the Microvasculature of Human Gastric Carcinomas, Anticancer Research 29:449–454 (2009) (“Caruso”). 6 Richardson et al., US 2006/0188492 A1, published Aug. 24, 2006 (“Richardson”). 7 Bell et al., Pericytes Control Key Neurovascular Functions and Neuronal Phenotype in the Adult Brain and during Brain Aging, Neuron 68, 409–427 (2010) (“Bell”). 8 Comeau et al., US 2006/0039910 A1, published Feb. 23, 2006 (“Comeau”). Appeal 2020-003932 Application 15/031,141 5 which is detecting a natural phenomenon wherein pericytes are located throughout the body.” Id. The Examiner further finds that “[t]he administration of fluorescent markers and detection of the fluorescent markers throughout the body are routine and customary.” Id. In support of this position, the Examiner cites to Hirase. The Examiner finds that Hirase “teaches of the administration of dextran fluorescent markers (e.g. Calcium Green I dextran) to selectively label a plurality of pericytes and the detection of pericytes.” Id. A. Principles of Law 1. Section 101 An invention is patent-eligible if it claims a “new and useful process, machine, manufacture, or composition of matter.” 35 U.S.C. § 101. However, the U.S. Supreme Court has long interpreted 35 U.S.C. § 101 to include implicit exceptions: “[l]aws of nature, natural phenomena, and abstract ideas” are not patentable. E.g., Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216 (2014). In determining whether a claim falls within an excluded category, we are guided by the Court’s two-part framework, described in Mayo and Alice. Id. at 217–18 (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 75–77 (2012)). In accordance with that framework, we first determine whether the claim recites a judicial exception. See Alice, 573 U.S. at 219 (“On their face, the claims before us are drawn to the concept of intermediated settlement, i.e., the use of a third party to mitigate settlement risk.”); see also Bilski v. Kappos, 561 U.S. 593, 611 (2010) (“Claims 1 and 4 Appeal 2020-003932 Application 15/031,141 6 in petitioners’ application explain the basic concept of hedging, or protecting against risk.”). If the claim is “directed to” a judicial exception—a law of nature, a natural phenomenon, or an abstract idea—we turn to the second step of the Alice and Mayo framework, where “we must examine the elements of the claim to determine whether it contains an ‘inventive concept’ sufficient to ‘transform’ the claimed abstract idea into a patent-eligible application.” Alice, 573 U.S. at 221 (quotation marks omitted). “If a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself.” Mayo, 566 U.S. at 77. 2. USPTO Section 101 Guidance In January 2019, the U.S. Patent and Trademark Office (USPTO) published revised guidance on the application of § 101. 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50 (Jan. 7, 2019) (“2019 Revised Guidance”).9 “All USPTO personnel are, as a matter of internal agency management, expected to follow the guidance.” Id. at 51; see also October 2019 Update at 1. 9 The Office issued further guidance on October 17, 2019. USPTO, October 2019 Update: Subject Matter Eligibility (the “October 2019 Update”) (available at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.p df). Appeal 2020-003932 Application 15/031,141 7 Under the 2019 Revised Guidance and the October 2019 Update, we first look to whether the claim recites: (1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes) (“Step 2A, Prong One”); and (2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)–(c), (e)–(h) (9th ed. Rev. 08.2017, Jan. 2018)) (“Step 2A, Prong Two”).10 2019 Revised Guidance, 84 Fed. Reg. at 52-55. Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look, under Step 2B, to whether the claim: (3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or (4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (“Step 2B”). 2019 Revised Guidance, 84 Fed. Reg. at 52–56. 10 This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. See 2019 Revised Guidance — Section III(A)(2), 84 Fed. Reg. 54–55. Appeal 2020-003932 Application 15/031,141 8 B. Revised Guidance Step 2A, Prong 1 Following the Revised Guidance, we first consider whether the claims recite a judicial exception. Claims 1 and 10 both recite the steps of “acquiring . . . fluorescence signals originating from labeled pericytes to produce pericyte information associated with tissues of the subject’s body” and “identifying a subject condition using the pericyte information.” The Revised Guidance identifies “a law of nature, or a natural phenomenon” as being among the judicial exceptions to patentability. 84 Fed. Reg. at 54. Here, we agree with the Examiner that the correlation between pericyte information and certain conditions is a natural phenomenon. The Specification discloses that pericyte information may be used in identifying a condition such as a neural degeneration condition elicited by epilepsy. Spec. ¶ 7. According to the Specification, “such pericyte information can include information related to pericyte functionality, morphology, location, size, number, separation, spatial distribution, and so on.” Id. at ¶ 35. In Mayo, the Court held that “Prometheus’ patents set forth laws of nature—namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.” 566 U.S. at 77. Similarly here, Appellant’s claims set forth laws of nature—namely, relationships between the pericyte information (e.g., location, size, number, spatial distribution), and certain conditions. Therefore, claims 1 and 10 recite a judicial exception to patentability. Appeal 2020-003932 Application 15/031,141 9 With regard to claim 21, however, we find that it does not recite a judicial exception. Claim 21 recites a method for staining pericytes by administering intravenously an effective amount of an injectable solution comprising fluorescently conjugated dextran that selectively binds to pericytes in the subject. These steps do not recite or describe any recognized exception. See Mayo Collaborative Svcs. v. Prometheus Labs., 566 U.S. 66, 78 (2012) (recited steps of administering a drug to a patient and determining the resultant level of 6-thioguanine in the patient “are not themselves natural laws”); see also USPTO May 2016 Subject Matter Eligibility Examples11 (finding claim 1 of Example 29, reciting a method of detecting JUL-1 in a patient, to be patent eligible). C. Revised Guidance Step 2A, Prong 2 Even though claims 1 and 10 recite a natural phenomenon, they would still be patent-eligible if “the claim as a whole integrates the recited judicial exception into a practical application of the exception.” 2019 Revised Guidance, 84 Fed. Reg. at 54. “A claim that integrates a recited judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the judicial exception.” Id. 11 Available at https://www.uspto.gov/sites/default/files/documents/101_examples_1to36.p df. Appeal 2020-003932 Application 15/031,141 10 The analysis of determining whether the claim integrates the judicial exception into a practical application includes “[i]dentifying whether there are any additional elements recited in the claim beyond the judicial exception(s)” and “evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application.” Id. at 54–55. Appellant asserts that “the examiner fails to perform step 2A, prong 2 of the test upon asserting that the claims were directed toward a judicial exception” by “fail[ing] to analyze whether the claim is integrated into a practical application.” Appeal Br. 5. We agree with Appellant. Claims 1 and 10 both recite the additional step of “administering intravenously to a subject an effective amount of an injectable solution comprising fluorescent conjugated Dextran markers . . . to selectively label pericytes throughout the subject’s body.” The Examiner did not conduct an analysis as to whether the additional elements in this step (or other additional elements recited in the claims), individually or in combination, integrate the exception into a practical application. Instead, the Examiner discusses “routine, and conventional activities” which are the relevant considerations for Step 2B, rather than Step 2A, Prong 2. See Ans. 12. Therefore, we find that the Examiner did not sufficiently establish that claims 1 and 10 do not have additional elements that integrate the exception into a practical application. Appeal 2020-003932 Application 15/031,141 11 D. Revised Guidance Step 2B Furthermore, even if the Examiner had properly conducted such an analysis under Step 2A, Prong 2, these claims would still be eligible under Step 2B because the Examiner failed to show that the step of administering intravenously an effective amount of an injectable solution comprising fluorescent conjugated Dextran markers to selectively label pericytes throughout a subject’s body was routine or conventional. The Revised Guidance directs us to consider whether claim 1 includes “additional elements . . . [that] provide[] ‘significantly more’ than the recited judicial exception.” 84 Fed. Reg. at 56. The Revised Guidance states that an additional element that “simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, . . . is indicative that an inventive concept may not be present.” Id. However, an additional element that “[a]dds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, . . . is indicative that an inventive concept may be present.” Id. “The question of whether a claim element or combination of elements is well-understood, routine and conventional to a skilled artisan in the relevant field is a question of fact.” Berkheimer v. HP Inc., 881 F.3d 1360, 1368 (Fed. Cir. 2018). “Whether a particular technology is well-understood, routine, and conventional goes beyond what was simply known in the prior art. The mere fact that something is disclosed in a piece of prior art, for Appeal 2020-003932 Application 15/031,141 12 example, does not mean it was well-understood, routine, and conventional.” Id. at 1369. “In rejecting an application, factual determinations by the PTO must be based on a preponderance of the evidence.” In re Oetiker, 977 F.2d 1443, 1449 (Fed. Cir. 1992) (J. Plager, concurring). In this case, the Examiner cites to Hirase as evidence that “the administration of a fluorescent marker to a subject and detection of the fluorescent marker is routine and customary in the prior art.” Final Act. 3. We first note that the Examiner describes the routine nature of the generic concept of the administration and detection of fluorescent markers but fails to provide evidence that the intravenous administration of Dextran markers to selectively label pericytes throughout a subject’s body was well-understood, routine, or conventional. Second, for the reasons discussed below with respect to the rejections under 35 U.S.C. § 103, we find that Hirase does not disclose such intravenous administration. We recognize that novelty and non-obviousness are not the test of eligibility under Section 101. See Data Engine Techs. LLC v. Google LLC, 906 F.3d 999, 1011 (Fed. Cir. 2018). However, the Examiner has not put forward any additional evidence to establish that such intravenous administration was “routine and customary.” Therefore, for the reasons discussed above, we reverse the Examiner’s rejections of claims 1, 4–10, 13–16, and 21–24 under 35 U.S.C. § 101 as being directed to patent-ineligible subject matter. Appeal 2020-003932 Application 15/031,141 13 Rejection of claims 1, 5 and 7 under 35 U.S.C. § 103(a) as obvious over Hirase. The Examiner finds that Hirase “discloses a method for identifying a subject condition comprising administering to a subject an effective amount of an injectable solution comprising fluorescent markers (e.g. Calcium Green I dextran) to selectively label a plurality of pericytes in the subject’s body.” Non-Final Act.12 3 (citing Hirase Abstract, 98). The Examiner further finds that “[t]he selective in vivo labeling of pericytes with functional markers may help reveal their physiological function in neuronal activity- associated regulation of local cerebral blood flow” and that Calcium Green I dextran has a molecular weight of 10kD. Id. at 3–4 (citing Hirase 96). Appellant contends that Hirase does not teach intravenous administration of dyes for labeling of pericytes but, rather, teaches an invasive approach for locally labeling pericytes that requires direct focal injection of dyes. Appeal Br. 13. Specifically, Appellant asserts that “Hirase states that ‘no methods are known to label pericytes selectively’ and provides a new process for labeling brain pericytes involving removing a piece of bone from the skull and infusing a dextran-containing dye via a glass pipette in the visual cortex.” Id. at 12 (citing Hirase 95, 96). The Examiner responds that “Hirase teaches in vivo administration but in a different manner” and that “[i]t would have been obvious to the skilled artisan to examine intravenous administration for the clear advantage of eliminating the need for an invasive approach.” Ans. 13. The Examiner 12 Non-Final Action mailed Sept. 17, 2018 (“Non-Final Act.”). Appeal 2020-003932 Application 15/031,141 14 further finds that “[p]ericytes are found throughout the body and therefore, it would have been expected that pericytes, located throughout the body, can be labeled with dextran dyes without the need for administration through the skull.” Id. We agree with Appellant that Hirase does not render obvious the intravenous administration of Dextran markers to selectively label pericytes throughout a subject’s body. As discussed by Appellant, Hirase discloses a method for labeling pericytes by removing a piece of the skull and inserting the dextran-containing dye via a pipette into the visual cortex. Hirase 96. After such dye administration, it was found that “pericytes are labeled on a small subset of vessels” and that “[i]n addition to pericytes, astrocytes and capillary endothelial cells were also labeled in the vicinity (~300 µm) of the injection site.” Id. at 96, 98. We do not find that, based on this teaching, it would have been obvious to one of ordinary skill in the art to administer Dextran dyes intravenously to achieve selective labeling of pericytes throughout a subject’s body nor would the artisan have a reasonable expectation of success that such administration would be able to selectively label such pericytes based on the teachings of Hirase. Rather than disclosing an intravenous administration of dye, Hirase discloses an invasive procedure for pericyte labeling, which does not even appear to be entirely selective (i.e., astrocytes and capillary endothelial cells were also labeled near the injection site). Id. When Hirase does disclose intravenous administration of a dye, it is to visualize the cerebral vasculature to distinguish from the labeled pericytes. Id. at 98. Furthermore, Hirase does not disclose or Appeal 2020-003932 Application 15/031,141 15 suggest selectively labeling pericytes throughout the entire body. In fact, Hirase discloses that “labeling at distant sites was sparse.” Id. Thus, we find that Hirase does not render the claims obvious and the Examiner’s reasoning that a skilled artisan would have expected to be able to selectively label pericytes throughout the body using intravenous dye administration is based on improper hindsight. “The Patent Office has the initial duty of supplying the factual basis for its rejection. It may not . . . resort to speculation, unfounded assumptions or hindsight reconstruction to supply deficiencies” in the cited references. In re Warner, 379 F.2d 1011, 1017 (CCPA 1967). Therefore, for the reasons discussed above, we reverse the Examiner’s rejections of claims 1, 5, and 7 as being obvious over Hirase. Rejection of claims 1, 4–10, 13–16, and 21–23 under 35 U.S.C. § 103(a) as obvious over Choi in view of Guerin, Caruso, and Hirase and further in view of Richardson, Bell, and Comeau The Examiner finds that Choi “teaches that in order to examine pericytes surrounding the retinal vessels, immunofluorescence staining of angiography with infusion of TMR-D (10 mg/ml) was performed to dye to the blood vessels and pericytes with the pericyte marker αSMA.” Final Act. 7. The Examiner further finds that even though Choi does not explicitly disclose intravenous administration, it does teach visualizing pericytes after infusion of TMR-D. Id. The Examiner also finds that Guerin discloses “leakage of fluorescent dextrans to demonstrate the breakdown of the blood- brain barrier” and that “[p]ericytes of both leaky and non-leaky vessels in Appeal 2020-003932 Application 15/031,141 16 affected areas were sometimes strongly labelled with low molecular weight dextrans.” Non-Final Act. 8–9. The Examiner further finds that Caruso “teaches that pericytes exhibit several types of surface contact with endothelial cells, including gap junctions, adhesion plaques and peg-socket junctions wherein the gap junctions provide direct connections between the cytoplasm of the two cells and allow the passage of ionic currents and small molecules” and that Hirase shows “pericytes at junction points of blood vessels.” Final Act. 8. The Examiner acknowledges that Caruso does not teach intravenous administration of solutions for labeling pericytes but concludes that, “it would have been obvious to one of ordinary skill in the art that leakage at the junctions of Hirase will allow for labeling of pericytes with fluorescent conjugated dextran markers as pericytes are located at these junctions and that pericytes may also be labeled via other types of junctions, such as that of Caruso.” Id.; Ans. 16. The Examiner appears to rely on Richardson, Bell, and Comeau for the rejection of certain dependent claims. Appellant argues, inter alia, that the cited references, alone or in combination, do not teach or suggest “administering intravenously to a subject an effective amount of an injectable solution comprising fluorescent conjugated Dextran markers, having a molecular weight in a range between 3 kiloDaltons and 70 kiloDaltons, to selectively label pericytes throughout the subject’s body.” Appeal Br. 18. We agree with Appellant that the teachings of Choi in view of Guerin, Caruso, and Hirase and further in view of Richardson, Bell, and Comeau do Appeal 2020-003932 Application 15/031,141 17 not render the claims obvious. As discussed above regarding the obviousness rejection over Hirase alone, none of the references cited by the Examiner teach the intravenous administration of Dextran markers to selectively label pericytes throughout the subject’s body. With regard to Choi, the Examiner acknowledges that Choi “was not used to teach [] intravenous administration,” but, rather was used to teach utilizing “the imaging information and data provided by the administration of TMR-D diabetic patients to view the number of pericytes and vessel leakage to determine whether there is pericytic loss and identify retinal diseases as pericyte loss and BRB breakdown are characteristic features in early diabetic retinopathy.” Ans. 14–15. The Examiner relies on Guerin to teach that “pericytes of both leaky and non-leaky vessels in affected areas were sometimes strongly labelled with low molecular weight dextrans.” Id. at 15. However, Guerin does not teach selective labeling of pericytes throughout the body. As pointed out by Appellant, the control animals of Guerin did not show any pericyte labeling. Furthermore, although Guerin teaches that “[s]ome pericytes in affected areas internalized [] low molecular weight dextrans,” this labeling does not appear to have been selective because endothelial cells were also labeled along with the pericytes. See Guerin 875, 880, Fig. 4. The Examiner has also not established that the pericyte labeling of Guerin was throughout the subject’s body. In addition, the Examiner has not sufficiently established a motivation to combine Guerin with the other cited references. The studies of Guerin “were undertaken to investigate the dynamics of blood-brain barrier Appeal 2020-003932 Application 15/031,141 18 breakdown in an in vivo rat model of selective CNS vulnerability.” Id. at 873. The Examiner relies on Guerin for teaching that “pericytes of both leaky and non-leaky vessels in affected areas were sometimes strongly labelled with low molecular weight dextrans” but does not provide any rationale as to why one of ordinary skill in the art would combine the teachings of Choi and Guerin. With regard to Hirase and Caruso, the Examiner finds that “it would have been obvious to one of ordinary skill in the art that leakage at the junctions of Hirase will allow for labeling of pericytes with fluorescent conjugated dextran markers as pericytes are located at these junctions and that pericytes may also be labeled via other types of junctions, such as that of Caruso.” Id. Ans. 15, 16. However, as discussed above, Hirase does not teach the intravenous administration of Dextran markers for selectively labeling pericytes throughout the body. Similarly, we agree with Appellant that “Caruso does not teach intravenous administration of solutions (but rather works with surgically resected specimens), does not teach labeling pericytes in any way, and does not teach using any type of fluorescent conjugated Dextran markers.” Appeal Br. 20. The Examiner has not sufficiently established why the combination of Guerin with Hirase or Caruso (or the other cited references), would have rendered the claims obvious. “We must still be careful not to allow hindsight reconstruction of references to reach the claimed invention without any explanation as to how or why the references would be combined to produce the claimed invention.” Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363, 1374 n.3 Appeal 2020-003932 Application 15/031,141 19 (Fed. Cir. 2008). The other references cited by the Examiner do not cure these deficiencies. Therefore, for the reasons discussed above, we reverse the Examiner’s rejections of claims 1, 4–10, 13–16, and 21–23 as being obvious over Choi in view of Guerin, Caruso, and Hirase and further in view of Richardson, Bell, and Comeau. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 4–10, 13– 16, 21–24 101 Eligibility 1, 4–10, 13– 16, 21–24 1, 5, 7 103(a) Hirase 1, 5, 7 1, 4–10, 13– 16, 21–23 103(a) Choi, Guerin, Caruso, Hirase, Richardson, Bell, Comeau 1, 4–10, 13– 16, 21–23 Overall Outcome 1, 4–10, 13– 16, 21–24 REVERSED Copy with citationCopy as parenthetical citation