Ex Parte Bandholtz et alDownload PDFPatent Trial and Appeal BoardNov 6, 201714148483 (P.T.A.B. Nov. 6, 2017) 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. 14/148,483 01/06/2014 Lisa Charlotta Bandholtz 4008664-186890A 4023 23570 7590 11/08/2017 PORTER WRIGHT MORRIS & ARTHUR, LLP INTELLECTUAL PROPERTY GROUP 41 SOUTH HIGH STREET 29TH FLOOR COLUMBUS, OH 43215 EXAMINER POLIAKOVA-GEORGAN, EKATERINA ART UNIT PAPER NUMBER 1674 NOTIFICATION DATE DELIVERY MODE 11/08/2017 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): ipdocket @ porterwright .com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte LISA CHARLOTTA BANDHOLTZ, ALEXANDER GIELEN, AREZOU ZARGARI, OLIVER VON STEIN, and LARS-GORAN AXELSSON1 Appeal 2017-001646 Application 14/148,483 Technology Center 1600 Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and JOHN G. NEW, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL appellants state that the real party-in-interest is Index Pharmaceuticals AB. App. Br. 1. Appeal 2017-001646 Application 14/148,483 SUMMARY Appellants file this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1, 2, 4, 5-10, 18-21 as unpatentable under 35 U.S.C. § 102(b) as being anticipated by Von Stein et al. (WO 2007/050034 Al, May 3, 2007) (“Von Stein”).2 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CFAIMED INVENTION Appellants’ invention is directed to methods for the treatment of inflammatory diseases of the central nervous system by administration of an oligonucleotide in an amount sufficient to reduce the influx of mononuclear cells to the central nervous system by down-regulating the expression of at least one cell surface marker. Abstract. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A method for the treatment and/or alleviation of multiple sclerosis by inhibiting or reducing the influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker, the method comprising administering an 2 The Examiner also rejected claims 1, 3, 7, 8, 11, 14, 15, 18-25 as unpatentable under 35 U.S.C. § 102(b) as being anticipated by Bachman et al. (WO 2005/004907 Al, January 20, 2005) (“Bachman”). Final Act. 2-3. This rejection has been withdrawn by the Examiner. See Advisory Act. 2 (October 9, 2015). 2 Appeal 2017-001646 Application 14/148,483 oligonucleotide to a multiple sclerosis patient in need thereof in an amount effective to inhibit or reduce the influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker, wherein the oligonucleotide is an isolated oligonucleotide selected from the group consisting of G*G*A*ACAGTTCGTCCAT*G*G*C (SEQ ID NO: 9) (IDX0150) and G*G*GGGACGATCGTCG*G*G*G*G*G (SEQ ID NO: 10) (IDX0980), wherein* represents phosphorothioate modification. App. Br. 15. ISSUES AND ANALYSES We agree with, and adopt, the Examiner’s findings of fact and conclusions that the appealed claims are anticipated by the cited prior art. We address the arguments raised by Appellants below. A. Rejection of claims E 2, 4-10 and 18-21 Issue Appellants argue the Examiner erred in finding that the claims are anticipated because Von Stein neither discloses nor enabled the limitations of claim 1. App. Br. 8-9. Analysis The Examiner finds Von Stein discloses a method of treatment of an inflammatory condition, including multiple sclerosis, by administering CG- containing immunomodulatory oligonucleotides and, specifically, Von Stein’s disclosed SEQ ID NO: 1, which is identical to Appellants’ SEQ ID 3 Appeal 2017-001646 Application 14/148,483 NO: 9. Final Act. 2 (citing Von Stein 1, 24, 25, 29). The Examiner finds that Von Stein discloses that the oligonucleotides can be administered via the intranasal route. Id. (citing Vons Stein 19). The Examiner further finds that Von Stein discloses that pharmaceutical compositions of the invention can include liposome-containing formulations and saline, and that dosage of oligonucleotide can be 1 pg per kg of body weight. Id. (citing Von Stein 21-23). The Examiner acknowledges that Von Stein is silent with respect to downregulation of specific surface markers or VEGF by the claimed oligonucleotide, but finds that those limitations describe, in the absence of evidence to the contrary, properties that are inherent to the oligonucleotide. Final Act. 2. Appellants argue that Von Stein fails to expressly disclose treatment and/or alleviation of multiple sclerosis. App. Br. 7. Appellants also contend that Von Stein does not disclose any administration of an oligonucleotide to “a multiple sclerosis patient,” as required by the claims. Id. Appellants point out further that none of the exemplary embodiments of Von Stein are directed to methods of treating multiple sclerosis. Id. Appellants argue that Von Stein is also silent with respect to the central nervous system and does not provide any disclosure of a method in which the influx of mononuclear and/or autoaggressive cells to the central nervous system of a multiple sclerosis patient is inhibited or reduced by down-regulating the expression of at least one specific cell surface marker. Id. at 7-8. Appellants contend further that, because Von Stein does not disclose any treatment of “a multiple sclerosis patient,” as required by claim 1, the claimed effects are not inherent in any of Von Stein’s teachings. App. Br. 8. 4 Appeal 2017-001646 Application 14/148,483 Furthermore, argue Appellants, since Von Stein does not disclose the central nervous system, or any means for down-regulating specific cell surface markers, a person of ordinary skill in the art would have had no expectation that any of Von Stein’s oligonucleotides could inhibit or reduce an influx of mononuclear and/or autoaggressive cells to the central nervous system by downregulating the expression of at least one specific cell surface marker. Id. Therefore, Appellants assert, if a person skilled in the art sought a method to inhibit or reduce an influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker, there would be nothing in von Stein that would lead one skilled in the art to employ Von Stein's oligonucleotides. Id. Consequently, Appellants argue, does not place the public in possession of any method for treating and/or alleviating multiple sclerosis, or a method in which the influx of mononuclear and/or autoaggressive cells to the central nervous system is inhibited or reduced by downregulating the expression of at least one specific cell surface marker. Id. The Examiner responds that the Von Stein discloses administration of specific oligonucleotides, including Appellants’ oligonucleotide SEQ ID NO: 9, to reduce inflammation associated with multiple sclerosis. Ans. 3. The Examiner finds that inhibition of specific cells of central nervous system will necessarily occur as part of a mechanism of the activity of the oligonucleotide in the body of a patient. Id. The Examiner finds that Appellants’ claims are drawn to a method of treatment and/or alleviation of multiple sclerosis and Von Stein discloses methods to alleviate inflammation stemming from multiple sclerosis. Ans. 3. The Examiner finds that, although the precise manner by which the 5 Appeal 2017-001646 Application 14/148,483 administered oligonucleotide alleviates inflammation is not disclosed, administration of the same oligonucleotide to a patient with multiple sclerosis would be expected to carry out the same functions leading to alleviation of inflammation caused by multiple sclerosis, including inhibiting or reduction of an influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker. Id. The Examiner finds that that von Stein also discloses that administration of the SEQ ID NO: 9 oligonucleotide can induce endogenous production of interferons and IL-10 in ulcerative colitis patients, increasing the efficacy of steroid treatment. Ans. 3—4 (citing Von Stein 46 47). The Examiner points out that Appellants have adduced no evidence to show that the same or a similar mechanism will not work for alleviating symptoms of multiple sclerosis: the Examiner finds that it is well known in the art that steroids are used in the treatment of multiple sclerosis. Id. at 4. The Examiner also notes that Appellants’ claims are drawn to a method comprising administering an oligonucleotide and, therefore can include a method using steroids in combination with the claimed oligonucleotide for treatment of multiple sclerosis. Id. The Examiner also finds that Example 14 of Von Stein expressly discloses, in an exemplary embodiment, that treatment with oligonucleotide combined with steroid administration were effective, whereas Example 15 discloses that treatment with oligonucleotides (and not steroids or other medications) were not effective. Ans. 4. The Examiner therefore finds that Von Stein discloses that administration of the claimed oligonucleotide improves treatments with other medications, including steroids, which, the 6 Appeal 2017-001646 Application 14/148,483 Examiner notes, are well known in the treatment of multiple sclerosis. Id. Therefore, the Examiner finds, the Examples do not preclude treatment of multiple sclerosis with the claimed oligonucleotide in combination with steroid treatment. Id. Furthermore, because the claims recite: “the method comprising administering an oligonucleotide to a multiple sclerosis patient,” the Examiner finds that such combination treatment is within the scope of the claims on appeal. Id. We are not persuaded by Appellants’ arguments. Anticipation under 35 U.S.C. § 102 requires that “all limitations of the claim are found in the reference, or ‘fully met’ by it.” Kalman v. Kimberly-Clark Corp., 713 F.2d 760, 772, (Fed. Cir. 1983). However, a reference may anticipate inherently if a claim limitation that is not expressly disclosed “is necessarily present, or inherent, in the single anticipating reference.” Verizon Servs. Corp. v. Cox Fibernet Va., Inc., 602 F.3d 1325, 1337 (Fed. Cir. 2010). The Examiner finds, and Appellants do not dispute, that Von Stein discloses the oligonucleotide of Appellants’ SEQ ID NO: 9 and its administration to a patient in the treatment of inflammatory diseases. See Von Stein 1 (“The present invention relates to the prevention, treatment and/or alleviation of inflammatory diseases”). Moreover, Von Stein expressly discloses that multiple sclerosis is an inflammatory disease. See id. Appellants contend that Von Stein fails to explicitly disclose the limitation of claim 1 reciting “administering an oligonucleotide to a multiple sclerosis patient in need thereof in an amount effective to inhibit or reduce the influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell 7 Appeal 2017-001646 Application 14/148,483 surface marker.” Furthermore, Appellants argue that Von Stein would fail to enable a person of ordinary skill from practicing the claimed invention. We do not agree. We acknowledge Appellants’ argument that Von Stein provides no exemplary embodiments directed to the treatment of a patient with multiple sclerosis, but we are not persuaded that Von Stein therefore does not anticipate Appellants’ claims. Von Stein discloses that: “The present invention relates to the prevention, treatment and/or alleviation of inflammatory diseases” and that such inflammatory diseases comprise: “allergic conditions, asthma, allergic rhinitis, inflammatory bowel disease (Crohn’s disease and related conditions), multiple sclerosis, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, and cardiovascular diseases with an inflammatory component.” Von Stein 1 (emphasis added). Von Stein thus expressly teaches that multiple sclerosis is an inflammatory diseases to which the disclosed method of Von Stein can be directed. For the purposes of whether they are anticipatory, lists and genera are often treated differently under our case law. This distinction collapses when the class of compounds that falls within the genus is so limited that a person of ordinary skill in the art can “at once envisage each member of this limited class.” In that limited circumstance, a reference describing the genus anticipates every species within the genus In re Gleave, 560 F.3d 1331, 1337-1338 (Fed. Cir. 2009) (internal references omitted); see also Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1376 (Fed.Cir.2005) (rejecting “the notion that [a compound] cannot anticipate because it appears without special emphasis in a longer list”). 8 Appeal 2017-001646 Application 14/148,483 Although Gleave addresses the question of whether a genus of compounds anticipates a given species, rather than a list of given inflammatory conditions to be treated, we nevertheless determine that the same principle applies in the appeal before us. Von Stein expressly discloses a genus comprising a relatively short list of inflammatory diseases, such that a person of ordinary skill in the art of treating inflammatory diseases could envision each member of this limited class. We therefore conclude that a person of ordinary skill would have understood that the disclosures of Von Stein could be directed to the treatment of, inter alia, multiple sclerosis via administration to a patient. Furthermore, we agree with the Examiner that Von Stein inherently discloses those limitations of claim 1 not expressly disclosed by the reference. Von Stein discloses the same oligonucleotide claimed. “From the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing.” In re Papesch, 315 F.2d 381, 391 (CCPA 1963). Therefore, the claimed properties are inherent in the disclosed oligonucleotide of Von Stein, once administered. Von Stein discloses that: Effective amounts of immunomodulating oligonucleotides for enhancing steroid efficacy in a steroid resistant or steroid dependent patient would broadly range between about 0.01 pg to about 100 mg per kg of body weight, preferably about 0.1 pg to about 10 mg, and most preferably about 1 pg to about 5 mg per kg of body weight of a recipient mammal Von Stein 22-23. Appellants’ Specification discloses: “According to an embodiment, the oligonucleotide is administered in an amount of about 1 to about 2000 pg per kg body weight, preferably about 1 to about 1000 pg per 9 Appeal 2017-001646 Application 14/148,483 kg body weight. Most preferably the oligonucleotide is administered in an amount of about 1 to 500 pg per kg body weight.” Specification 56; see also dependent claims 19-21. These ranges disclosed by Appellants’ Specification are each contained within the range disclosed as the most preferable dosage range by Von Stein. Furthermore, Von Stein discloses: “In the inventive method the CG containing immunomodulatory oligonucleotides can be administered by any appropriate administration route, such as, but not limited to, inhalation, ophthalmic, intranasal, parenteral, oral, intradermal and rectal administration.” Von Stein 19. Appellants’ Specification discloses: “In a method according to the invention, the route of administration is chosen from mucosal, subcutaneous, intramuscular, intravenous and intraperitoneal administration. According to an embodiment of the method, the mucosal administration is chosen from nasal, oral, gastric, ocular, rectal, urogenital and vaginal administration.” Spec. ^ 57. There is, therefore, a strong overlap in the methods of administration disclosed by Von Stein and Appellants’ Specification. It therefore follows that, in administering a dosage of Appellants’ oligonucleotide SEQ ID NO: 9 in the dosage range and via the routes of administration disclosed by Von Stein, the administration of the oligonucleotide must necessarily have the effect of: “inhibiting] or reducing] the influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker,” as recited in claim 1. We therefore conclude that Von Stein inherently teaches the disputed limitations of the claims. See Agilent Technologies, Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 10 Appeal 2017-001646 Application 14/148,483 2009) (The “very essence of inherency is that one of ordinary skill in the art would recognize that a reference unavoidably teaches the property in question”). Moreover, and for much the same reasons, we are not persuaded that Von Stein does not enable Appellants’ claimed invention. Von Stein recognizes multiple sclerosis as an inflammatory disease treatable by its disclosed methods. Von Stein 1. Von Stein also teaches dosages and routes of administration of Appellants’ oligonucleotide SEQ ID NO: 9 that directly encompass those disclosed by Appellants’ Specification. A person of ordinary skill in the art, practicing the disclosures of Von Stein in these respects would necessarily elicit the responses recited by Appellants’ claim 1. Finally, where, as here, [T]he claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . . . Whether the rejection is based on ‘inherency’ under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, 562 F.2d 1252, 1255 (C.C.P.A. 1977). Appellants have adduced no evidence to demonstrate that the dosages and methods of administering Appellants’ oligonucleotide SEQ ID NO: 9 disclosed by Von Stein would not have produced the effects recited in claim 1. Appellants have failed to meet this burden. 11 Appeal 2017-001646 Application 14/148,483 We consequently affirm the Examiner’s rejection of the claims on this ground. B. Claims 2, 5, 6, 9 and 10 Issue Appellants also argue these claims separately. App. Br. 10. Appellants contend that, based upon the disclosures of Von Stein, a person of ordinary skill one of ordinary skill in the art would not have had any reasonable expectation that all inflammatory conditions could be treated by administration of SEQ ID NO: 1. Id. Analysis Appellants point to Examples 14 and 15 of Von Stein, which provide contrasting results in the treatment of ulcerative colitis and Crohn’s disease. App. Br. 10. Appellants assert that, in view of the contrasting results of Example 14, in which the administration of Appellants’ SEQ ID NO: 9 was therapeutically beneficial, and Example 15, in which administration did not appear to be therapeutically beneficial, a person of ordinary skill would not have had any reasonable expectation that all inflammatory conditions could be treated by administration of Appellants’ SEQ ID NO: 9. Rather, Appellants contend, in view of the contrasting results of Von Stein’s Examples 14 and 15, a skilled artisan have recognized Von Stein’s treatment of inflammatory conditions with Appellants’ SEQ ID NO: 9 was specific to (1) inflammatory conditions of the airway of a mammal, and (2) ulcerative colitis and Crohn's disease in patients who were on concomitant medication and were unresponsive to corticosteroids or corticosteroid dependent. 12 Appeal 2017-001646 Application 14/148,483 Therefore, Appellants assert, Von Stein does not enable the claimed method. Id. The Examiner finds that Example 14 of Von Stein discloses that, treatment with Appellants’ oligonucleotide SEQ ID NO: 9 combined with steroid administration were effective, whereas Example 15 discloses that treatment with oligonucleotides (and not steroids or other medications) were not effective. Ans. 4. The Examiner therefore finds that Von Stein discloses that administration of the claimed oligonucleotide improves treatments with other medications, including steroids, which, the Examiner notes, are well known in the treatment of multiple sclerosis. Id. Therefore, the Examiner finds, the Examples do not preclude treatment of multiple sclerosis with the claimed oligonucleotide in combination with steroid treatment. Id. Furthermore, because the claims recite: “the method comprising administering an oligonucleotide to a multiple sclerosis patient.” Such combination treatment is within the scope of the claims on appeal. Id. We agree with the Examiner’s reasoning. The claim language reciting “comprising” expressly contemplates additional constituents to the claimed methods, including the administration of steroids, which the Examiner finds, and Appellants do not dispute, are well known in the treatment of inflammatory diseases, including multiple sclerosis. See Crystal Semiconductor Corp. v. TriTech Microelectronics Inti, Inc., 246 F.3d 1336, 1348 (Fed. Cir. 2001) (“Use of the transition “comprising” in the language of a claim creates a presumption ... that the claim does not exclude additional, unrecited elements”). We therefore agree with the Examiner that a person of ordinary skill in the art would understand, upon apprising the disclosures of Von Stein, that Example 14 discloses combining treatment of 13 Appeal 2017-001646 Application 14/148,483 Appellants’ oligonucleotide with steroids in steroid resistant or dependent patients would be an effective treatment and within the scope of Appellants’ claims. We therefore affirm the rejection of the claims. C. Claims 4 and 6 Issue Appellants also argue these claims separately. App. Br. 11. Claim 4 is representative and recites: “The method according to claim 1, wherein the cell surface marker is at least one of CD49d, CXCR3 (CD 183), CCR2 (CD192), and CCR5 (CD195).” Id. at 15. Appellants argue that Von Stein fails to disclose any method in which the influx of mononuclear and/or autoaggressive cells to the central nervous system is inhibited or reduced by downregulating the expression of at least one specific cell surface marker selected from CD49d, CXCR3 (CD 183), CCR2 (CD 192), and CCR5 (CD 195) as recited in claim 4 and, specifically, by down-regulating the expression of at least one CD49d. Id. We are not persuaded by Appellants’ arguments. As we have explained supra, Von Stein teaches the administration of Appellants’ oligonucleotide SEQ ID NO: 9 in the same dosages and via the same routes of administration as disclosed by Appellants’ Specification. We therefore agree with the Examiner that such administration would necessarily, and thus inherently, result in which the influx of mononuclear and/or autoaggressive cells to the central nervous system is inhibited or reduced by downregulating the expression of at least one specific cell surface marker selected from CD49d, CXCR3 (CD 183), CCR2 (CD 192), and CCR5 (CD 195) as recited in claim 4 and, specifically, by down-regulating the 14 Appeal 2017-001646 Application 14/148,483 expression of at least one CD49d, as disclosed by Appellants’ Specification. See, e.g., Spec. ^ 47, Example 2. We therefore affirm the Examiner’s rejection on this ground. D. Claims 19-21 Issue Appellants also argue these claims separately. App. Br. 13. Claim 19 is representative and recites: “The method according to claim 1, wherein the oligonucleotide is administered in an amount of about 1 to about 2000 pg per kg body weight.” Id. at 16. Appellants argue that Von Stein fails to disclose administration of an oligonucleotide of SEQ ID NO: 9 in an amount of about 1 to about 2000 pg per kg body weight, about 1 to about 1000 pg per kg body weight, or about 1 to 500 pg per kg body weight is effective to inhibit or reduce an influx of mononuclear and/or autoaggressive cells to the central nervous system by down-regulating the expression of at least one specific cell surface marker. Id. at 13. We are not persuaded by Appellants’ argument. As we have explained supra, Von Stein expressly teaches administration of Appellants’ oligonucleotide SEQ ID NO: 9 in the dosages recited in claims 19-21 and disclosed in Appellants’ Specification. See Von Stein 22-23, Spec. ^ 56. We therefore find that administration of Appellants’ oligonucleotide SEQ ID NO: 9 at these dosages would necessarily, and therefore inherently, result in the effects recited in claim 1 and disclosed by Appellants’ Specification. See, e.g., Spec. Fig. 10. We consequently affirm the Examiner’s rejection of the claims. 15 Appeal 2017-001646 Application 14/148,483 DECISION The Examiner’s rejection of claims 1, 2, 4-10 and 18-21 as unpatentable under 35 U.S.C. § 102(b) 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)(1). See 37 C.F.R. § 1.136(a)(l)(iv). AFFIRMED 16 Copy with citationCopy as parenthetical citation