Ex Parte Shi et alDownload PDFPatent Trial and Appeal BoardFeb 8, 201710901481 (P.T.A.B. Feb. 8, 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. 7814/111 8464 EXAMINER AKHOON, KAUSER M ART UNIT PAPER NUMBER 1642 MAIL DATE DELIVERY MODE 10/901,481 07/28/2004 Riyi Shi 7590757 BGL P.O. BOX 10395 CHICAGO, IL 60610 02/08/2017 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RIYI SHI, RICHARD B. BORGENS, and RAPHAEL C. LEE Appeal 2016-002017 Application 10/901,481 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and ERICA A. FRANKLIN, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35U.S.C. § 134 involving claims to a method for treating a mammalian patient having suffered an injury to nerve tissue of the central nervous system. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. Statement of the Case Background “Mechanical damage to the nervous system of mammals results in sometimes irreversible functional deficits” (Spec. 1:29—30). “In the CNS 1 Appellants identify the Real Party in Interest as The University of Chicago (see App. Br. 3). Appeal 2016-002017 Application 10/901,481 [central nervous system], distal segments of nerve fibers do not regenerate, and their loss produces nonfunctional ‘target’ cells, which often require innervation to maintain their integrity. One ultimate strategy to enhance recovery from CNS injury is to induce or facilitate regeneration of white matter” (Spec. 3:9-12). “The invention is more particularly directed to the application or administration of an effective amount of a biomembrane fusion agent... to the site of an injury ... to nerve tissue, particularly nerve tissue of the spinal cord or the peripheral nervous system.” (Spec. 6:23—27). The Claims Claims 2—11, 14, and 16—32 are on appeal. Claim 21 is representative and reads as follows: 21. A method for treating a mammalian patient having suffered an injury to nerve tissue of the central nervous system, the method comprising administering an effective amount of a composition comprising an amphipathic polymer comprising a polar substructure and a nonpolar substructure wherein the administrating is effective in delivering the effective amount to a site of nerve tissue injury in the mammalian patient’s central nervous system by way of a vascular route, and wherein the effective amount is administered after the injury occurs and is an amount that increases the conduction of action potentials in injured nerve tissue and increases at least one of reflex behavior, motor function and sensation in the patient. 2 Appeal 2016-002017 Application 10/901,481 The issues The Examiner rejected claims 2—11, 14, and 16—32 under 35 U.S.C. § 103(a) as obvious over Lee,2 Borgens,3 and Follis4 (Ans. 4—10). The Examiner finds “Lee teaches a method for the treatment of tissue injury caused by electrical injury (after injury occurs), and includes peripheral nerve necrosis among the damages associated with electrical trauma ... by administering a poloxamer. a bio-membrane fusion agent, by intravenous administration” (Ans. 4—5). The Examiner acknowledges that “Lee does not explicitly recite wherein the patient suffered injury to the CNS, or that the effective amount is an amount that ‘increases conduction of action potential in injured nerve tissue and increases at least one of reflex behavior, motor function and sensation’” (Ans. 6). The Examiner finds “Borgens teaches treatment of spinal cord injury through repair of membranes” and teaches “polymers treatment to injured nerve tissue increases nerve impulse conduction and increases spinal cord dependent behavior, such as reflex, motor and sensation” (Ans. 6). The Examiner finds “Follis teaches the role of poloxamer 188 (PI 88) in treatment of ischemic paraplegia. Follis teaches intravenous delivery of PI88 to animals with paraplegia and measuring hind limb function” (Ans. 7). 2 Lee, R., US 5,605,687, issued Feb. 25, 1997 (“Lee”). 3 Richard B. Borgens and Riyi Shi, Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol, 14 FASEB J. 27-35 (2000) (“Borgens”). 4 Follis et al., Role of Poloxamer 188 During Recovery From Ischemic Spinal Cord Injury: A Preliminary Study, 9 J. Investigative Surgery 149-56 (1996) (“Follis”). 3 Appeal 2016-002017 Application 10/901,481 The Examiner finds it obvious “to use the method of treating CNS nerve tissue injury to spinal cord injury or ischemic injury, as taught by Borgens and Follis and use an alternative surfactant, such as poloxamer by injection as per Lee” (Ans. 7). The issue with respect to these rejections is: Does the evidence of record support the Examiner’s conclusion that Lee, Borgens, and Follis render obvious administering an amphipathic polymer to the central nervous system by a vascular route as required by independent claims 19,21, and 32? Findings of Fact 1. Lee teaches treatment of electrical injury. The invention is directed to methods and compositions for the treatment of cell membrane damage and tissue injury caused by the disruption of cell membrane integrity following electrical injury. In particular, the invention concerns the treatment of tissue damage and the enhancement of cell survival through the sealing of permeabilized cell membranes by administering an effective amount of a composition comprising a surface-active copolymer, and more preferably, through the co-administration of a surface-active copolymer and a high energy phosphate compound. (Lee 1:11-22). 2. Lee teaches “[vjictims of major electrical trauma frequently suffer extensive skeletal muscle and nerve damage which is postulated to be mediated partly by cell membrane permeabilization” (Lee 5:38-40). 3. Lee teaches “injection of a pharmaceutical composition comprising a sterile filtered poloxamer ... is expected to result in rapid 4 Appeal 2016-002017 Application 10/901,481 reversal of cell membrane permeabilization following electrical injury” (Lee 8:28-33). 4. Lee teaches “[djepending upon the nature of the injury and the copolymer used, the pharmaceutical composition containing the copolymer, or copolymer and high energy phosphate compound, may be administered topically, intravenously, intramuscularly or subcutaneously” (Lee 4:1—5). 4. Borgens teaches a “brief application of the hydrophilic polymer polyethylene glycol (PEG) swiftly repairs nerve membrane damage associated with severe spinal cord injury in adult guinea pigs” (Borgens, abstract). 5. Borgens teaches an “aqueous solution of PEG . . . was applied with a pipette to the exposed injury for 2 min in experimental animals and then removed by aspiration” (Borgens 28, col. 1). 6. Borgens teaches that “19 of the 22 sham-treated animals did not recover CTM functioning” while “CTM functioning recovered in 10 of 14 PEG-treated animals” (Borgens 30, col. 1—2). 7. Follis teaches “Poloxamer 188 (P188) has been shown in the experimental animal to increase regional blood flow to ischemic areas. . . . We conclude that intravenous administration of PI 88 before, during, and for 48 hours after aortic cross-clamping does not prevent paraplegia or improve the long term neurologic outcome'1'’ (Follis, abstract). 8. Follis teaches “our study did not show any beneficial effect of Poloxamer 188 in the rat model of spinal cord ischemia. The compound did not prevent the occurrence of paraplegia nor did it improve the long-term 5 Appeal 2016-002017 Application 10/901,481 neurologic outcome, although it did ameliorate the rate of recovery of the neurologic function in the first week” (Follis 155). Principles of Law A prima facie case for obviousness requires “a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does.” KSR Int 7 Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Analysis Appellants contend “there is no suggestion of a method of treating injury to the central nervous system including the delivery of an amphipathic polymer by way of the patient’s vascular system to a site of injured nerve tissue in the central nervous system” and that “Borgens teaches that a polymer should be instead applied directly to the exposed injury (i.e., NOT via the vascular system)” (App. Br. 5). The Examiner responds “Mezrow is used to indicate/provide evidence that poloxamer passes the blood-brain-barrier (bbb) and this was known prior to Appellant’s invention. Contrary to their assertion and the myriad of references provided by Appellant that at the time of the invention poloxamer was not known for passing the bbb” (Ans. 13). We find that Appellants have the better position because while Lee teaches intravenous treatment of nerve damage with poloxamer and Borgens suggests the use of PEG for treatment of spinal cord injury (FF 1—6), we agree with Appellants that neither reference suggests that amphipathic polymers “cross[] the blood-brain barrier to be effective in treating as injury to the central nervous system” (App. Br. 7). Neither Lee nor Borgens 6 Appeal 2016-002017 Application 10/901,481 provide a reason to intravenously administer an amphipathic polymer to the central nervous system because there would be no expectation of success as evidenced by Follis who teaches “intravenous administration of PI 88 before, during, and for 48 hours after aortic cross-clamping does not prevent paraplegia or improve the long term neurologic outcome” (FF 7; italics omitted). That is, Follis, a reference cited by the Examiner, teaches that intravenous administration of a poloxamer “did not show any beneficial effect” (FF 8). The Examiner relies upon Mezrow5 to rebut Appellants’ position and the Lee Declaration6 that the prior art would not expect poloxamers to cross the blood-brain-barrier (see App. Br. 7). Mezrow teaches that “P188-treated dogs were given a loading dose before CPB [cardiopulmonary bypass] and received an infusion of the drug for 6 hours after DHCA [deep hypothermic circulatory arrest]” (Mezrow 1144, col. 1—2). Mezrow teaches the “precise mode of action of PI 88 remains controversial”; that the “copolymer has the ability to bind to damaged membranes, prevent further injury, and maintain cellular integrity”; that the “rheologic properties of PI 88 appear to be due to its ability to increase blood flow in ischemic or damaged tissue” and that investigators “found the copolymer to increase blood flow to ischemic brain in rabbits” (Mezrow 1145, col. 1—2). 5 Mezrow et al., Poloxamer 188 improves neurologic outcome after hypothermic circulatory arrest, 103 J. Thoracic and Cardiovascular Surgery 1143-6(1992) (“Mezrow”). 6 Declaration of Dr. Raphael C. Lee, dated Feb. 27, 2014 (“Lee Declaration”). 7 Appeal 2016-002017 Application 10/901,481 Our review finds no evidence in Mezrow supporting the Examiner’s position that PI88 or any other poloxamer passes through the blood-brain- barrier. Any beneficial effects of the poloxamer in Mezrow on neurohistologic damage might reasonably have been attributed by Mezrow to improved blood flow (see Mezrow 1145, col. 2) and not to direct action on the central nervous system tissue by the poloxamer. The Examiner does not specifically identify any evidence that the poloxamer directly interacts with central nervous system tissue in Mezrow. We agree with Appellants that “Mezrow speculates that although the mode of action of PI 88 is controversial, its rheologic properties may be due to its ability to increase blood flow and in doing so to prevent tissue damage. Such a mode of action does not indicate delivery of the polymer across the blood-brain barrier to the site of injury in the CNS” (Reply Br. 4). Conclusion of Law The evidence of record does not support the Examiner’s conclusion that Lee, Borgens, and Follis render obvious administering an amphipathic polymer to the central nervous system by a vascular route as required by independent claims 19, 21, and 32. SUMMARY In summary, we reverse the rejection of claims 2—11, 14, and 16—32 under 35 U.S.C. § 103(a) as obvious over Lee, Borgens, and Follis. REVERSED 8 Copy with citationCopy as parenthetical citation