Ex Parte StewartDownload PDFPatent Trial and Appeal BoardMay 10, 201814030000 (P.T.A.B. May. 10, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/030,000 09/18/2013 63467 7590 Ramey & Schwaller, LLP 5020 Montrose Blvd. Suite 750 Houston, TX 77006 05/14/2018 FIRST NAMED INVENTOR Duncan John Stewart 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. 20200.0002.PCUS02 1029 EXAMINER KELLY, ROBERT M ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 05/14/2018 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@rameyfirm.com wramey@rameyfirm.com bwilliams@rameyfirm.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Exparte DUNCAN JOHN STEWART 1 Appeal2016-007734 Application 14/030,000 Technology Center 1600 Before FRANCISCO C. PRATS, JOHN G. NEW, and JOHN E. SCHNEIDER, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 Appellant identifies Northern Therapeutics, Inc. as the real party-in- interest. App. Br. 3. Appeal2016-007734 Application 14/030,000 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner's Final Rejection of claims 21, 23-25, and 28 as unpatentable under 35 U.S.C. § 112, first paragraph, for lack of enablement. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellant's invention is directed to a cell-based therapy comprising administration to the lung, by injection into the blood system, of viable, mammalian cells effective for alleviating or inhibiting pulmonary disorders. Abstract. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 21. A process for alleviating or inhibiting the progression of mechanically induced acute lung injury in a mammalian patient comprising administration of syngeneic or allogeneic or autologous mesenchymal stem cells, smooth muscle cells, fibroblast cells or a combination thereof to the lung by injection into the pulmonary circulation of the mammalian patient suffering from the disorder wherein the administration results in alleviation or inhibition of the progression of the acute lung injury. App. Br. 25. Appellant has selected, as the elected species under examination and on appeal, non-transformed mesenchymal stem cells ("MSCs"), and ARDS ""Acute Respiratory Distress Syndrome") (as the acute lung injury). Final Act. 2 (citing Reply Br. December 17, 2014). 2 Appeal2016-007734 Application 14/030,000 ISSUE AND ANALYSIS We agree with, and adopt, the Examiner's findings and conclusion that the appealed claims are not enabled by Appellant's Specification. Issue 1 Appellant argues that the Examiner erred in finding that Appellant's Specification, although being enabling for treatment of LPS-induced ALI rodent models of ARDS, does not reasonably provide enablement for treatment of ALI in other species. App. Br. 12 (citing Final Act. 5). Analysis The Examiner finds that Appellant's Specification discloses that administered mesenchymal stem cells lodge in the lung at the capillaries, and thereby effect treatment. Final Act. 5. The Examiner finds Example 22 of the Specification discloses that such cell therapy works in mice with ALI that has been induced by lipopolysaccharides ("LPS"). Id. The Examiner further finds that the Specification discloses the treatment of ARDS and a description of its clinical manifestations. Id. (citing Spec i-fi-1 6-9). The Examiner finds that human subjects are specifically included for treatment Id. (citing, e.g., Spec. i1288). However, the Examiner finds, the bulk of Appellant's Specification is directed to the administration of transgenic cells, wherein the transgene has the claimed therapeutic effect. Final Act. 5. The Examiner points to several references in support of the findings of fact. Final Act. 6. The Examiner finds that G. Matute-Bello et al., Animal Models of Acute Lung Injury, 295 AM. J. LUNG CELL MOL. PHYSIOL., L379-99 (2008) ("Matute-Bello") teaches the effects of LPS-induced 3 Appeal2016-007734 Application 14/030,000 models for ARDS/ ALI in several animals are evaluated as models of ARDS. Id. (citing Matute-Bello L384-86). The Examiner finds that Matute-Bello teaches that the response to an LPS insult is species specific, requiring varying administration dosages of LPS, and that the model, in general, "does not cause the severe endothelial and epithelial injury that occurs in humans with ARDS." Id. (citing Matute-Bello L386). The Examiner then points to D.N. Kotton, et al., Bone Marrow- Derived Cells as Progenitors of Lung Alveolar Epithelium, 128 DEVELOPMENT' 5181-88 ("Kotton"). Final Act. 6. The Examiner finds Kotton teaches a different model of ALI, bleomycin-induced ARDS, for which treatment with a simple administration of mesenchymal stem cells ("MSCs") was ineffective. Id. The Examiner next points to S.H.J. Mei et al., Prevention of LPS- Induced Acute Lung Injury in Mice by Mesenchymal Stem Cells Overexpressing Angiopoietin 1, 4(9) PLoS MEDICINE, 1525-37 (2007) ("Mei")2. The Examiner finds that Mei expressly states that: "it should be emphasized that the animal model used here is not a precise parallel of ARDS in humans, and that more research remains to be done before human studies of this sort could be considered." Id. (quoting Mei 15 3 7). The Examiner therefore concludes that a person of ordinary skill, comprehending the data disclosed by Appellant's Specification, would have considered that more information would be required to reasonably predict treatment in other species, particularly humans, without having to perform 2 The Examiner notes that Appellant is one of the authors of this reference. Final Act. 6. 4 Appeal2016-007734 Application I 4/030,000 undue experimentation. Final Act. 6. The Examiner finds that the cited references and Appellant's Specification collectively teach that the various models are not entirely accurate models of ARDS because they do not completely reproduce the features of ARDS and, therefore, that the claimed treatment would not be equally effective across the approximately 5500 extant species of mammal. Id. Appellant argues that there are at least three working examples in the application that provide enablement for at least Claim 2 I. App. Br. I 4. According to Appellant, at least Examples I9, 22, and 23 teach one of skill in the art to make and use the subject matter of claim 2 I. Id. Appellant contends that Example I 9 teaches treating ARDS in rats with smooth muscle cells expressing Angiopoeitin- I. Id. Example 22, asserts Appellant, teaches preventing ALI (an important underlying cause of human ARDS) in mice with mesenchymal cells overexpressing Ang- I. Id. Appellant argues that Example 23 teaches treating ARDS in rats and mice with fibroblast cells expressing Ang-I. Id. Appellant quotes our reviewing court, stating that: "it has long been recognized that when experimentation on human subjects is inappropriate, as in the testing and development of drugs and medical devices, the enablement requirement may be met by animal tests or in vitro data." App. Br. I4 (quoting Edwards Lifesciences AG v. Core Valve, Inc., 699 F.3d I305, I309-IO (Fed. Cir. 20I2). Appellant argues that the fact pattern of the instant appeal is congruent with those in Edwards: both sets of claims relate to medical therapies or devices that were tested in animal models. App. Br. I 5. Appellant notes that the Federal Circuit's decision in Edwards supports Appellant's position that an enablement rejection requiring testing in 5 Appeal2016-007734 Application 14/030,000 humans, simply because more developmental work is required at the time of filing the application, is improper. Id. With respect to the references cited by the Examiner, Appellant argues that the Examiner's reliance on Matute-Bello fails to specifically address the claims and in doing so, has failed to show that the claims are not enabled for treatment of ALI. App. Br. 16. Appellant points to Claim 21 as being directed to treating ALI. Id. Appellant specifically points out that the first sentence of Matute-Bello teaches that ALI is not the same as ARDS: "Acute lung injury (ALI) and its most severe manifestation, the acute respiratory distress syndrome (ARDS), is a clinical syndrome defined by acute hypoxemic respiratory failure, bilateral pulmonary infiltrates consistent with edema, and normal cardiac filling pressures." Id. (quoting Matute-Bello 379). Appellant asserts, therefore, that Matute-Bello teaches that ARDS is ALI but not all ALI is ARDS. Id. (emphasis added). With respect to Kotton, Appellant argues that the Examiner has not demonstrated where Kotton teaches that no treatment was found by administration of MSCs. App. Br. 16. Appellant contends that Kotton is not evidence that the disclosure of the present application fails to make and use the claimed invention. Id. Appellant also points to Exhibit 11, a declaration filed by the inventor in a related application, US Ser. No. 11/696,039, April 16, 2012 (the "Stewart Declaration"), which explains that one cannot determine whether Kotton discloses a method of treating ARDS with mesenchymal stem cells based upon the time of various aspects of the experiment. Id. Appellant contends that the Stewart Declaration also states that LPS administration in a mouse model to initiate ARDS symptoms correlates with ARDS symptoms in humans. Id. at 16-1 7. 6 Appeal2016-007734 Application 14/030,000 With respect to Mei, Appellant notes that the editor of the reference states that the mouse model was not "a precise parallel" to the human condition. App. Br. 17. It is not necessary that an animal model be a precise parallel to enable a claim to humans, argues Appellant, but, rather, "all that is required is a reasonable correlation between the activity and asserted use." Id. (quoting MPEP § 2107.03.I. Appellant adduces several references to show that the rat model of ALI/ ARDS using LPS-induced pulmonary inflammation is accepted by persons of skill in the art. App. Br. 19. Appellant points first to D. Rocksen, ACUTE LUNG INWRY: STUDY OF PATHOGENESIS AND THERAPEUTIC INTERVENTIONS (2003) ("Rocksen") as teaching that: Experimental animal models are useful tools for better understanding of the underlying mechanisms of ALI/ ARDS and may be helpful in development of therapy to prevent the human disease. A plethora of models has been used to elicit ALI/ ARDS in animals, but the most extensively used is inhalation exposure or systemic administration of bacterial endotoxin (lipopolysaccharide: LPS), Id. (quoting Rocksen 29). Appellant notes that Rocksen also teaches that: "Exposure to moderate doses LPS has been used as a prototypic model of ALI in several studies and intratracheal administration of high doses in rats has been suggested as a relevant model of ARDS in one study." Id. (quoting Rocksen 30) (references omitted). Appellant quotes Rocksen as concluding that: "[W]e have demonstrated that the generalized Shwartzman reaction in mice exhibits a lung pathology that resembles clinical features of ARDS, as evidenced by acutely impaired respiratory function leading to mortality as well as characteristic hallmarks of ARDS such as lung edema and interstitial neutrophil infiltration" and that "In this thesis, experimental animal models 7 Appeal2016-007734 Application 14/030,000 of ALI/ ARDS have been used in order to achieve a comprehensive knowledge of which cells and mediators are involved in the pathogenesis of the syndrome." Id. (quoting Rocksen 44--45, 55). Appellant also points to S. Lax et al., Using a Non-Invasive Assessment of Lung Injury in a Murine Model of Acute Lung Injury, 1 BMJ OPEN RESP. RES., 1-8 (2014) ("Lax"), as teaching that: "Intratracheal (IT) LPS is a very reproducible technique which models many of the features in human ALI, typified by significant infiltration of neutrophils into the alveolar air spaces and expression of pulmonary inflammatory cytokines" and that: "Animal models are used to replicate pathological, physiological and histological changes in human ALI/ARDS. 3" App. Br. 19 (quoting Lax 1) Appellant next points to D. Rittirsch et al., Acute Lung Injury Induced by Lipopolysaccharide is Independent of Complement Activation, 180 J. IMMUNOL., 7664--72 (2008) ("Rittirsch"), which states: "Therefore, lung injury induction by LPS in rodents represents a frequently used ALI model, mimicking many features of ALI/ ARDS in humans." App. Br. 20 (quoting Rittirsch 7670). Finally, Appellant argues that "[g]rants received from a funding source indicate that an animal model is accepted as predictive of clinical efficacy. Grant proposals may request funding for conducting in vivo experiments on animal models or for clinical experiments." App. Br. 20. Appellant points to a number of grants and grant proposals as indicative that 3 Appellant notes that, whereas Lax was published in 2014, the article was received and accepted by the journal in 2013 and, therefore, Appellant contends that it indicates the thoughts of an artisan in 2013. App. Br. 20. 8 Appeal2016-007734 Application I 4/030,000 animal models using mesenchymal stem cells in the development of treatments for, inter alia, LPS-induced ALI and treatment of ARDS in clinical trials. Id. at 20-2I (citing Exs. I2-I4). We are not persuaded by Appellant's arguments. Appellant has chosen, as the elected species of claim 2 I, non-transformed MSCs as the cells to be administered for the alleviation or inhibition of the progression of ARDS. Final Act. 25. It is, therefore, this species which we must determine whether Appellant's Specification enables. Appellant points primarily to Examples I 9, 22, and 23 of the Specification as enabling disclosures of claim 2 I. See App. Br. I 4. Example I 9 of the Specification is directed to using transfected smooth muscle cells derived from the pulmonary artery and expressing angiopoeitin- I ("Ang-I") to treat mechanically-induced ALI (pulmonary edema) in rats. Spec. i-fi-12 I 8-220. Claim I 9 is therefore not directed to the elected species because it does not employ either non-transformed or transformed mesenchymal stem cells in the treatment of ARDS, which is the human clinical correlate of severe ALI. See Spec. i1 6. Similarly, claim 23 is directed to the use of transfected fibroblast cells expressing Ang-I in the treatment ofLPS-induced ALI in rats. Spec. i-fi-1 265-267. Appellant contends that this LPS-induced model is recognized as a close model of ARDS in humans. See App. Br. I9. However, we again find that this example is not enabling for the claims because it does not disclose the use of MS Cs, either transformed or non-transformed. Claim 22 of the Specification is directed to the treatment of LPS- induced ALI in rats with transfected MSCs expressing Ang- I. Spec. i-fi-1 259-59. This is the sole example in the Specification disclosing the use of 9 Appeal2016-007734 Application 14/030,000 MSCs in the treatment of ALI. Furthermore, Example 23 discloses the use of both transformed and non-transformed (i.e., control) MSCs and further discloses that the non-transformed MSCs had a beneficial effect on the LPS- induced ALI. See Spec. i-f 262 ("Treatment with MSCs alone reduced total protein, albumin and IgM levels modestly"); see also Figs. 33A---C. Claim 22 thus discloses the use of non-transformed MS Cs in the treatment of LPS- induced ALI, which, Appellant asserts, is a close, and therefore enabling, model for human ARDS. However, that is not the end of our analysis. Appellant's claim 21 is directed to: "A process for alleviating or inhibiting the progression of mechanically induced acute lung injury in a mammalian patient." (Emphasis added). Example 19 of the Specification discloses the use of smooth muscle cells in treating mechanically-induced ALI and is therefore not enabling for the elected species (i.e., non-transformed MSCs ). Example 22 discloses the use of non-transformed (and transformed) MSCs in the treatment of LPS- induced ALI, which Appellant asserts is a close and enabling model for ARDS. Claim 22, however, is not by itself enabling on claim 21 because it does not teach treatment of mechanically-induced (as opposed to LPS- induced) ALI or ARDS. Thus, none of the Examples relied upon by Appellant are directly enabling for claim 21. We therefore address the question of whether some combination of the Examples, or other disclosures of the Specification, are enabling for the elected species of claim 21. We conclude that they do not. Appellant has adduced a number of references, i.e., Rocksen, Lax, Rittirsch, and Exhibits 12-14, to argue that LPS-induced ALI is an accurate model for human ARDS, the latter of which is also part of the Appellant's elected species. 10 Appeal2016-007734 Application 14/030,000 However, Appellant has adduced no persuasive evidence of record to demonstrate that a person of ordinary skill in the art would understand that mechanically-induced ALI, as recited in claim 21, in rats is a sufficiently precise model of human ARDS to enable the claim. Indeed, Appellant directly admits that Matute-Bello teaches that not all models of ALI in rats are the same as human ARDS, which is the elected species. See App. Br. 16 ("Matute-Bello teaches that ARDS is ALI but not all ALI is ARDS"). Absent evidence of record that a person of ordinary skill in the art would understand that mechanically-induced ALI is ARDS, or a reasonably predictive model of ARDS, we conclude that Appellant's Specification is not enabling for claim 21. The Specification provides no examples or embodiments of the elected species, nor are there other any disclosures of the Specification, that suggest that mechanically-induced ALI in rats is a model of human ARDS such that it could be treated by non-transformed MSCs. We consequently affirm the Examiner's rejection of claim 21. Furthermore, Appellant relies upon the same arguments with respect to dependent claims 23-25 and 28. App. Br. 23-24. We therefore, and for the same reasons, affirm the Examiner's rejection of these claims. DECISION The Examiner's rejection of claims 21, 23-25, and 28 as unpatentable under 35 U.S.C. § 112, first paragraph, for lack of enablement is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R. § 1.136(a)(l )(iv). 11 Appeal2016-007734 Application 14/030,000 AFFIRMED 12 Copy with citationCopy as parenthetical citation