Ex Parte Richardson et al

Patent Trials and Appeals BoardMar 18, 2019

14435306 - (D) (P.T.A.B. Mar. 18, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/435,306 04/13/2015 32425 7590 03/20/2019 NORTON ROSE FULBRIGHT US LLP 98 SAN JACINTO BOULEVARD SUITE 1100 AUSTIN, TX 78701-4255 FIRST NAMED INVENTOR Arlan Richardson 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. UTSK.P0427US/l 000222356 5300 EXAMINER HAVLIN, ROBERT H ART UNIT PAPER NUMBER 1639 NOTIFICATION DATE DELIVERY MODE 03/20/2019 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): aoipdocket@nortonrosefulbright.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ARLAN RICHARDSON, VERONICA GALVAN, AI-LING LIN, PETER FOX, and DANA M. VAUGHN Appeal2018-000921 Application 14/435,306 Technology Center 1600 Before JEFFREY N. FREDMAN, ELIZABETH A. LA VIER, and RACHEL H. TOWNSEND, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal 1,2 under 35 U.S.C. Â§ 134(a) involving claims to a method for treating vascular cognitive impairment using a coated rapamycin composition. The Examiner rejected the claims as indefinite and as obvious. We have jurisdiction under 35 U.S.C. Â§ 6(b ). We affirm. 1 Appellants identify the Real Party in Interest as The Board of Regents of The University of Texas System and the licensee, Rapamycin Holdings (see App. Br. 1). 2 We have considered the Specification of Apr. 13, 2015 ("Spec."); Final Office Action of Oct. 12, 2016 ("Final Act."); Appeal Brief of Mar. 13, 2017 ("Br."); and Examiner's Answer of July 27, 2017 ("Ans."). Appeal2018-000921 Application 14/435,306 Statement of the Case Background "Dementia or cognitive impairment refers to a set of symptoms that occur due to an underlying condition or disorder that causes loss of brain function" (Spec. ,r 4). "A common cause of vascular cognitive impairment is the occurrence of multiple small strokes ( called 'ministrokes ') that affect blood vessels and nerve fibers in the brain, which ultimately promotes symptoms of dementia or vascular cognitive impairment" (id. ,r 5). "Thus, vascular cognitive impairment is more common in those patients who are at risk for stroke, such as elderly patients, or patients having high blood pressure" (id. ,r 5). The Claims Claims 1, 3-11, 17, 18, 21, 25, 30-32, and 59 are on appeal. Independent claims 1 and 32 are representative and read as follows: 1. A method for treating vascular cognitive impairment, the method comprising administering an effective amount of a composition comprising rapamycin to a subject diagnosed as having vascular cognitive impairment; wherein the rapamycin is encased in a coating that includes a water insoluble polymer, wherein the water insoluble polymer is a methyl methacrylate- methacrylic acid copolymer. 32. A method for treating or preventing vascular cognitive impairment, the method comprising administering an effective amount of a composition comprising rapamycin to a subject diagnosed as having vascular cognitive impairment; wherein the rapamycin is encased in a coating that includes a water insoluble polymer, wherein the water insoluble polymer is a methyl methacrylate-methacrylic acid copolymer; and wherein the average tissue level of rapamycin in the subject is greater 2 Appeal2018-000921 Application 14/435,306 than 0.75 pg per mg of tissue after administration of the composition. The Issues A. The Examiner rejected claims 1, 3-11, 17, 18, 21, 25, 30-32, and 59 under 35 U.S.C. Â§ 112, second paragraph as indefinite (Ans. 5---6). B. The Examiner rejected claims 1, 3-11, 17, 18, 21, 25, 30-32, and 59 under 35 U.S.C. Â§ 103(a) as obvious over Azrolan, 3 Maitra, 4 Sharp, 5 and Chauhan6 (Ans. 2--4). C. The Examiner rejected claims 1, 3-11, 17, 18, 21, 25, 30-32, and 59 under 35 U.S.C. Â§ I03(a) as obvious over Azrolan, Maitra, Sharp, and Chauhan, and Cheng7 (Ans. 5). A. 3 5 U.S. C. Â§ 112, second paragraph The Examiner finds "one skilled in the art would have difficulty defining the scope of the claim because vascular cognitive impairment (VCI) diagnosis is not clearly defined and there is conflicting descriptions in the art" (Ans. 6). Appellants contend the "application clearly sets forth a definition of vascular cognitive impairment and methods for diagnosing vascular 3 Azrolan et al., WO 01/97809 A2, published Dec. 27, 2001. 4 Maitra et al., US 2008/0107749 Al, published May 8, 2008. 5 Sharp et al., WO 2010/05754 A2, published May 20, 2010. 6 Chauhan et al., Rapamycin protects against middle cerebral artery occlusion induced focal cerebral ischemia in rats, 235 BEHAVIOURAL BRAIN RES. 603-9 (2011). 7 Cheng et al., Rapamycin modulates the eNOS vs. shear stress relationship, 78 CARDIOVASCULAR RES. 123-9 (2008). 3 Appeal2018-000921 Application 14/435,306 cognitive impairment" (Br. 1, citing Spec. ,r,r 31-32). Specifically, Appellants cite paragraph 31 of the Specification, which states: The term "vascular cognitive impairment" refers to various defects caused by an underlying vascular pathology, disease, disorder, or condition that affects the brain. For example, strokes, conditions that damage or block blood vessels, or disorders such as hypertension or small vessel disease may cause vascular cognitive impairment. As used herein, the term "vascular cognitive impairment" includes mild defects, such as the milder cognitive symptoms that may occur in the earliest stages in the development of dementia, as well as the more severe cognitive symptoms that characterize later stages in the development of dementia. (Spec. ,-i 31 ). Appellants contend "the examples of the application demonstrate methods of detecting cerebral blood flow (para. [0082]) and methods for performing behavioral tests (para. [0084])" (Br. 2). We agree with Appellants. The term "vascular cognitive impairment" is not indefinite, but rather broad. That is, any impairment in cognition experienced by a patient due to damage to the patient's vasculature, whether caused by blockages, hypertension, or small vessel disease would broadly fall into the category of "vascular cognitive impairment." While we agree with the Examiner that the claims are broad, this breadth does not mean the claims are indefinite. In re Johnson, 558 F.2d 1008, 1016 n. 17 (CCPA 1977). Even "undue breadth is not indefiniteness." Id. 4 Appeal2018-000921 Application 14/435,306 B. and C. 35 U.S.C. Â§ 103(a) over Azrolan, Maitra, Sharp, and Chauhan Because these rejections tum on the same issues, Cheng is not required to address any of the claims, and Appellants do not specifically argue Cheng, we will consider these rejections together. The issue with respect to this rejection is: Does a preponderance of the evidence of record support the Examiner's conclusion that Azrolan, Maitra, Sharp, and Chauhan render the claims obvious? Findings of Fact 1. Azrolan teaches "a method of treating or inhibiting cardiovascular disease or peripheral vascular disease in a mammal in need thereof, which comprises providing an effective amount of a rapamycin to said mammal" where the "rapamycins of this invention are also useful inhibiting stroke or multiinfarct dementia" (Azrolan 3:21-23, 9:1-2). 2. Azrolan teaches "satisfactory results may be obtained when the rapamycin is administered in a daily oral dosage of from about 5 Âµg to 0.75 mg per kilogram of body weight" (Azrolan 10:2-3). 3. Maitra teaches "[r]apamycin was encapsulated in nanoparticles comprised of increasing order of acrylic acid[, ("AA")]" and that "[t]wo types of nanoparticles, each containing 20% molar ratio of AA (NV A622 and NMA622) demonstrate highest blood levels of rapamycin following oral delivery" (Maitra ,r 33). 4. Sharp teaches "microencapsulated rapamycin has been found to rescue cognition and attenuate the pathology in mouse models of Alzheimer disease" (Sharp 2). 5 Appeal2018-000921 Application 14/435,306 5. Sharp teaches coatings for the microencapsulated rapamycin include "a methyl methacrylate-methacrylic acid copolymer" (Sharp 3, cf Sharp 5). 6. Chauhan teaches "[r]apamycin treatment ameliorated motor impairment associated with MC Ao [ middle cerebral artery occlusion] and significantly reversed the changes in levels of malondialdehyde, glutathione, nitric oxide and myeloperoxidase" (Chauhan 603, abstract). 7. Chauhan teaches "[i]mpairment in motor co-ordination has been reported in the MCA occlusion model of cerebral ischemia" but "rapamycin treatment ameliorated the levels of MDA and MPO in ischemia- reperfusion injury models" (Chauhan 607, col. 2). Principles of Law "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). Analysis We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art (Ans. 2-5; FF 1-7) and agree that the claims are rendered obvious by Azrolan, Maitra, Sharp, and Chauhan. We address Appellants' arguments below. Claim 1 Appellants contend Azrolan fails to teach a treatment for subjects diagnosed with vascular cognitive impairment, which, according to the application, is cognitive impairment caused by vascular pathology. Specification, para. [0031]-[0032]. This specific condition is not taught in any cited references, and, therefore, 6 Appeal2018-000921 Application 14/435,306 none of the cited references can be cited for teaching a subject diagnosed with such disorder. (Br. 3). We find this argument unpersuasive whether Appellants intend to contest the obviousness of diagnosis prior to treatment or intend to contest the obviousness of rapamycin treatment of "vascular cognitive impairment" as interpreted in light of the Specification. Azrolan teaches treating vascular diseases including stroke and dementia (FF 1 ), and therefore reasonably suggests diagnosis because prior to treatment of a patient with a particular condition, an ordinary artisan would recognize that a physician must determine that the patient actually has the condition. Moreover, Sharp teaches treatment of mice determined (i.e., "diagnosed") to have a model of Alzheimer's disease (FF 4) and Chauhan teaches rapamycin treatment ameliorated motor impairment associated with mice with middle cerebral artery occlusion (FF 6). Thus, the combination of prior art, along with the knowledge of the ordinary artisan, would have reasonably suggested performing diagnosis prior to treatment. As to the term "vascular cognitive impairment", the Specification defines this term as including dementia, strokes, as well as "conditions that damage or block blood vessels" (Spec. ,r 31 ). Azrolan teaches treatment of both stroke and dementia, conditions that fall within the express definition of conditions that cause "vascular cognitive impairment" provided by the Specification (FF 1 ). Moreover, Sharp teaches rapamycin treatment of Alzheimer's disease, a type of dementia (FF 4) and Chauhan teaches rapamycin treatment of cerebral artery occlusion, a type of stroke (FF 6). Thus, the prior art reasonably teaches and suggests treatment of conditions that fall within the express definition of ones that cause "vascular cognitive 7 Appeal2018-000921 Application 14/435,306 impairment" provided by the Specification. See Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (en bane) ("[O]ur cases recognize that the specification may reveal a special definition given to a claim term by the patentee that differs from the meaning it would otherwise possess. In such cases, the inventor's lexicography governs."). Claim 32 Appellants contend "none of the references teach a treatment whereby 'the average tissue level of rapamycin in the subject is greater than 0.75 pg per mg of tissue after administration of the composition"' (Br. 3). We find this argument unpersuasive. Azrolan teaches treatment using a rapamycin dosage range "from about 5 Âµg to 0.75 mg per kilogram of body weight" (FF 2). The Specification teaches dosage ranges from "0.01 mg to about 500 mg of rapamycin" (Spec. ,r 57) and amounts including "1 microgram/kg/body weight" and "1 milligram/kg/body weight" (Spec. ,r 59). Thus, Azrolan teaches administration of overlapping dosage amounts with the dosages given in the Specification. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) ("In cases involving overlapping ranges, we and our predecessor court have consistently held that even a slight overlap in range establishes a prima facie case of obviousness."). To the extent that Appellants are arguing the dose that actually ends up in the tissue, rather than the starting dose, we agree with the Examiner that the dosages are routinely optimizable (see Ans. 7) and also find that the overlapping dosages of Azrolan would, in the absence of evidence to the contrary, inherently result in dosages exceeding the 0.75 pg/mg level required by claim 32. Indeed, because 0.75 pg/mg is equivalent to 0.75 8 Appeal2018-000921 Application 14/435,306 Âµg/kg, the upper limit of dosages of 0.75 mg/kg suggested by Azrolan exceeds the tissue amount by 1,000 fold (FF 2). Azrolan therefore reasonably shifts the burden to Appellants to demonstrate that treatment with rapamycin at Azrolan's suggested dosages, would not necessarily result in an "average tissue level of rapamycin in the subject ... greater than 0.75 pg per mg of tissue" as recited in the instant claim 32 because "[ w ]hether the rejection is based on 'inherency' under 35 U.S.C. Â§ 102, on 'prima facie obviousness' under 35 U.S.C. Â§ 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 (CCPA 1977). Appellants have provided no evidence showing that Azrolan's dosages would not have resulted in the claimed tissue levels. Claim 59 Appellants contend "[i]t is not apparent that the compositions of the cited art deliver the appropriate amount of rapamycin to a target tissue, such as the brain, as recited in claim 59 .... " (Br. 3). We find this argument unpersuasive. As already noted, Azrolan, Sharp, and Chauhan teach rapamycin treatment of disease conditions affecting the brain, including dementia (FF 1 ), Alzheimer's disease (FF 4 ), and middle cerebral artery occlusion (FF 6). Therefore, the prior art reasonably supports the Examiner's position that rapamycin treatment will treat brain tissue. Appellants provide no evidence that the dosages suggested by Azrolan, that overlap with those recited in the Specification, would have been insufficient to treat brain tissue. 9 Appeal2018-000921 Application 14/435,306 Conclusion of Law A preponderance of the evidence of record supports the Examiner's conclusion that Azrolan, Maitra, Sharp, and Chauhan renders the claims obvious. SUMMARY We reverse the rejection of 1, 3-11, 17, 18, 21, 25, 30-32, and 59 under 35 U.S.C. Â§ 112, second paragraph as indefinite. We affirm the rejection of claims 1, 32, and 59 under 35 U.S.C. Â§ 103(a) as obvious over Azrolan, Maitra, Sharp, and Chauhan. Claims 3- 11, 17, 18, 21, 25, 30, and 31 fall with claims 1, 32, and 59. We affirm the rejection of claims 1, 32, and 59 under 35 U.S.C. Â§ 103(a) as obvious over Azrolan, Maitra, Sharp, Chauhan, and Cheng. Claims 3-11, 17, 18, 21, 25, 30, and 31 fall with claims 1, 32, and 59. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.136(a)(l )(iv). AFFIRMED 10