Ex Parte Huston et alDownload PDFPatent Trial and Appeal BoardNov 8, 201711318075 (P.T.A.B. Nov. 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. 11/318,075 12/22/2005 Jared M. Huston 10642-703.200 9722 66854 7590 11/13/2017 SHAY TtT FNN T T P EXAMINER 2755 CAMPUS DRIVE D ABREU, MICHAEL JOSEPH SUITE 210 SAN MATEO, CA 94403 ART UNIT PAPER NUMBER 3762 NOTIFICATION DATE DELIVERY MODE 11/13/2017 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): info@ shayglenn.com shayglenn_pair @ firsttofile. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JARED M. HUSTON and KEVIN J. TRACEY Appeal 2016-0083501 Application 11/318,075 Technology Center 3700 Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and RYAN H. FLAX, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to a method for treating an inflammatory disorder in a subject comprising stimulating the vagus nerve with an electrical signal. The Examiner rejected the claims under 35 U.S.C. § 103 as obvious. We have jurisdiction under 35 U.S.C. § 6(b). The rejections are affirmed. 1 The Appeal Brief (“Appeal Br.”) identifies The Feinstein Institute for Medical Research as the real-party-in-interest. Appeal Br. 2. Appeal 2016-008350 Application 11/318,075 STATEMENT OF THE CASE Claims 1—12 and 34—39 are pending and stand rejected by the Examiner as follows: 1. Claims 1—4, 34, 36, 38, and 39 under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Boveja,2 Tracey,3 and Shafer.4 Ans. 2. 2. Claims 5—7 under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Boveja, Tracey, and Shafer. Ans. 4.5 3. Claims 8—12, 35, and 37 under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Boveja, Tracey, Shafer, and Whitehurst.6 Ans. 5.7 Claim 1, the only independent claim on appeal, is reproduced below (indentation added to emphasize the different limitations in the claim): 1. A method for treating inflammation in a subject suffering from an inflammatory disorder, the method comprising stimulating, in the subject suffering from inflammation, the subject’s vagus nerve with an electrical signal to achieve a therapeutic effect for treating the inflammation, wherein the signal voltage is from 0.01 Volt to 1 Volt, provided that the condition is not ileus, asthma or cystic fibrosis; and 2 U.S. Publ. Pat. Appl. 2005/0154425 Al, publ. July 14, 2005 (“Boveja”). 3 U.S. Publ. Pat. Appl. 2004/0204355 Al, publ. Oct. 14, 2004 (“Tracey”). 4 U.S. Publ. Pat. Appl. 2004/0172075 Al, publ. Sept. 2, 2004 (“Shafer”). 5 The Examiner stated that the rejection as set forth in the Final Action mistakenly cited Lesser. Ans. 4. The Examiner also omitted Shafer from the statement of the rejection in the Final Action. 6 U.S. Publ. Pat. Appl. 2003/0236557 Al, publ. Dec. 25, 2003 (“Whitehurst”). 7 The Examiner stated that the rejection as set forth in the Final Action mistakenly cited Lesser. Ans. 5. The Examiner also omitted Tracey and Shafer from the statement of the rejection in the Final Action. 2 Appeal 2016-008350 Application 11/318,075 waiting for at least 2 hours before restimulating the vagus nerve, wherein the therapeutic effect persists for at least 2 hours after stimulation has ended. FINDINGS OF FACT (“FF”) Boveia FF1. Boveja discloses vagus nerve electrical stimulation to provide therapy for neuropsychiatric disorders and cognitive impairments. Boveja 11- FF2. Boveja {id. 193) discloses “the approximate range of parameters” for vagus nerve stimulation as follow: TABLE 1 Electrical PiirnirrscScf mssse dolivovcd to She ticrvc PARAMER RANGE Pulse Amplitude 0.1 Volt—10 Volts Pulse width 20 iJS-5 msec. Frequency 5 Hz-200 Hz On-time 10 Sees-24 hours Off-linn; 10 Sees-24 hours Tracey FF3. Tracey teaches that “[stimulation of the efferent vagus nerve attenuates systemic inflammatory responses and inhibits TNF release.” Tracey 1 8. FF4. Tracey discloses electrical stimulation of the vagus nerve with 1 volt, 2 ms, and 1 Hz, resulted in suppression of TNF. Id. at || 106, 220, Fig. 5. 3 Appeal 2016-008350 Application 11/318,075 Shafer FF5. Shafer teaches that “it has been shown that electrical stimulation of the vagus nerve is capable of ameliorating immune activation . . . and is therefore useful in inhibiting inflammatory cytokine cascades that mediate several disease conditions.” Shafer 110. Lesser FF6. Lesser teaches vagal nerve stimulation has been used for seizures (Lesser 17), psychiatric disorders (id. | 8), neurological disorders (id.), pancreatic endocrine disorders (id.), sleep disorders (id.), eating disorders (id.), heart disorders (id. 19), and nausea and vomiting (id. 111). REJECTION 1 The Examiner found that Boveja describes treating a subject with vagal nerve stimulation where the electrical stimulation parameters (FF2) overlap with those that are claimed: Compare a signal voltage of 0.01—1 Volt recited in claim 1 to 0.1 Volt—10 Volts disclosed by Boveja (FF2). Compare an off-time of at least 2 hours recited in claim 1 to 10 seconds—24 hours disclosed by Boveja (FF2). Compare a pulse width of 0.1 ms—5 ms recited in claim 3 to 20 pS—5 ms (mSec) disclosed by Boveja (FF2). Compare a signal frequency of 0.1 Hz—30 Hz recited in claim 3 to 5Hz—200 Hz disclosed by Boveja (FF2). Compare a signal on-time of 1—120 seconds recited in claim 3 to 10 seconds—24 hours disclosed by Boveja (FF2). 4 Appeal 2016-008350 Application 11/318,075 The Examiner found that because the recited stimulation parameters “are the same” as those in Boveja, the therapeutic effect would persist for at least two hours after electrical stimulation as also required by the claim. Final Act. 3. The Examiner acknowledged that Boveja does not describe treating inflammation with electrical stimulation to the vagus nerve, but found that Tracey teaches vagal nerve stimulation for the same purpose as claimed (FF3, FF4) and specifically identified parameters of 1 Volt (compare claim 1 of 0.01—1 Volt), 2 ms (compare claim 3 of 0.1 ms—5 ms), and 1 Hz (compare claim 3 of 0.1 Hz—30 Hz). Final Act 3. The Examiner determined it would have been obvious to utilize the stimulation parameters of Boveja in Tracey (FF3) and Shafer (FF5) to treat inflammation. Id. Discussion Are the fields of endeavor different and consequently would there have been no reasonable expectation of success? Appellants contend that Tracey and Shafer are not in the same field of endeavor as Boveja and consequently one of ordinary skill in the art would not have sought to combine them to achieve the claimed method of treating inflammation. Appeal Br. 8. Appellants point out that Boveja is within the field of endeavor of treating neuropsychiatric disorders and cognitive impairment while “Shafer’s field of endeavor is treating cardiac inflammation and treating congestive heart failure and Tracey’s field of endeavor is treating inflammation.” Id. Appellants contend that “[bjecause the function of the prior art is different than the claimed function, the argument that it would be an ‘obvious design choice’ [as stated by the 5 Appeal 2016-008350 Application 11/318,075 Examiner] to modify Boveja to treat inflammation is improper.” Id. at 9. Appellants also contend there would have been no reasonable expectation of success that using the parameters of Boveja to treat inflammation would work when the mechanisms of action are different. Id. at 4, 8; Reply Br. 5— 6. This argument does not convince us that the Examiner erred. First, we do not agree that the fields of endeavor are so disparate that one of ordinary skill in the art would not have found Boveja’s vagal nerve teaching pertinent to the teaching of using vagal nerve stimulation to treat inflammation as taught Tracey and Shafer. All three publications utilize the same technology of nerve stimulation, making it reasonable for one of ordinary skill in the art to have looked to Boveja as guidance to determine stimulation conditions for the vagus nerve in Tracey and Shafer. ft is well-established that there are two criteria to be applied when determining whether a reference is analogous prior art: (1) whether the reference is from the “same field of endeavor” as the claimed invention, and (2) if the reference is not within the same field of endeavor, “whether the reference still is reasonably pertinent to the particular problem with which the inventor is involved.” In re Clay, 966 F.2d 656, 658—59 (Fed. Cir. 1992). In this case, the field of endeavor is vagal nerve stimulation. Appellants have defined it too narrowly, restricting the field to the narrower purpose for which the stimulation is applied. Fesser provides evidence that one of ordinary skill in the art was aware and considered it relevant that vagal nerve stimulation had been used to ameliorate a variety of different conditions (FF6), indicating that the skilled worker considered the field of endeavor to be broader than the narrower field defined by Appellants. 6 Appeal 2016-008350 Application 11/318,075 Appellants have not provided objective evidence to support their contention that the field of endeavor of the claims, Tracey, and Shafer is different from that of Boveja. Even if the fields of endeavor are different, it is reasonable that one of ordinary skill in the art would have looked to other fields in which vagal nerve stimulation had been accomplished as guidance to determine the optimal stimulation parameters because the same purpose is sought — to alleviate a medical condition experienced by a subject. As to the alleged lack of an expectation of success, we begin by summarizing the stimulation parameters of claims 1 and 3 as compared to those disclosed in Boveja and Tracy: Voltage Off- Time On- Time Pulse Width Frequency Claim 1 0.01-1 At least 2 hrs. Claim 3 1-120 sec. 0.1-5 msec. 0.1-30 Hz Boveja 0.1-10 10 secs- 24 hrs. 10 secs- 24 hrs. 20 psec — 5msec. 5-200 Hz Tracy 1 2 msec. 1 Hz As shown in the summary, the values in Tracey (cited by the Examiner on page 3 of the Final Action) overlap with Boveja in voltage and pulse width. Because of the overlap in stimulation parameters between Boveja and Tracey, one of ordinary skill in the art would had a reasonable expectation that Boveja’s parameters would work in Tracey’s method of stimulation. Accordingly, the Examiner’s determination that it would have been obvious to apply Boveja’s stimulation parameters for treating 7 Appeal 2016-008350 Application 11/318,075 neuropsychiatric disorders to Tracey is supported by a preponderance of the evidence. Thus, even if the mechanisms differ as argued by Appellants, the overlap between parameters reasonably suggests that a stimulation regime for treating a neuropsychiatric condition would work for treating inflammation. While the frequency value of 1 Hz disclosed in Tracey is less than the 5 Hz end point disclosed by Boveja, Boveja characterizes its values as “approximate” (FF2) and the five-fold difference (1 versus 5) is much less than 40-fold difference of Boveja’s entire range (5 to 200 or 40-fold difference between endpoints), indicating that a wide range of frequencies, are used to treat inflammatory conditions. Is two-hour waiting step obvious? Appellants contend that “the Examiner improperly dismisses this required two-hour waiting step [off-time] and the associated requirement that the therapeutic effect persist for at least two hours as inherent.” Appeal Br. 6. We do not agree. Boveja teaches a range of off-times of 10 secs to 24 hours (FF2) which overlaps with (or effectively encompasses) the claimed range of “at least 2 hours.” When there is a range disclosed in the prior art, and the claimed invention overlaps or falls within that range, there is a presumption of obviousness. In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). One of ordinary skill in the art would have reason to optimize the range to achieve the highest therapeutic effect. As held in Peterson, there is a “normal desire of scientists or artisans to improve upon what is already generally known.” Peterson, 315 F.3d at 1329-30. 8 Appeal 2016-008350 Application 11/318,075 Are the claimed ranges non-obvious? Appellants contend that the claimed ranges are critical and “wholly unexpected.” Appeal Br. 6; Reply Br. 3. Appellants’ argue: Boveja’s ranges for acceptably stimulating the vagus nerve overlap with but are not identical to the ranges recited in the claims. This is particularly significant where, as described in the Applicant’s specification, simulation outside of the claimed ranges of parameters may result in desensitization, resulting in either no therapeutic effect or a therapeutic effect that does not persist for at least two hours after stimulation. Appeal Br. 6. To support this contention, Appellants cite the following paragraphs from copending application Serial Number 12/259,208 (“hereinafter, “the ’208 Specification”) (emphasis added): [000138] The description above may be readily generalized to describe various parameters and effects for vagus nerve stimulation that are new and very unexpected. In particular, the extremely low level of stimulation (both low intensity, and low duty-cycle) have been seen to have a profound - and chronic - effect on the immune response. By low duty-cycle effect, we are referring to the time stimulation is “on” compared to the time stimulation is “off’ (e.g., the ratio of “on” to “off’). Thus, the stimulation (and particularly chronic stimulation) described herein is “off’ much more that in it is “on”. The high efficacy of these low duty-cycle modulation parameters is unexpected, and may have a profound effect on the wav that treatment of immune response (humor and/or cellular) are performed. For example, chronic (or long-term) stimulation may be effectively performed without the risk of negative effects associated with known stimulation protocols of the vagus nerve. [000139] Furthermore, the low-intensity (and low duty cycle) situation may be used safely without interfering with other aspects controlled by the vagus nerve. For example; altered 9 Appeal 2016-008350 Application 11/318,075 heart rate and blood pressure are not seen with the low- intensity, low duty-cycle modality stimulation. Thus, the vagus nerve may be stimulated either mechanically or electrically in a low-intensity and low duty-cycle fashion without desensitizing the vagus nerve or its targets, and without invoking a potentially unwanted physiological effect (e.g., on heart rate, heart tone, blood pressure, gastric processes, or any other effect attributed to vagal nerve stimulation except the targeted immune response). Both paragraphs 138 and 139 refer to “low-intensity” and “low-duty” stimulation. The ’208 Specification refers to voltage as an example of intensity. ’208 Spec. 148. The claimed range of intensity is from 0.01 Volt to 1 Volt. Appellants do not guide us to a definition of low-intensity that limits the range to that recited in claim 1. In addition, claim 1 is unrestricted as to the “time-on.” The ’208 Specification (| 138) indicates that the “time-on” refers to the duty-cycle (“[b]y low duty-cycle effect, we are referring to the time stimulation is ‘on’ compared to the time stimulation is ‘off’”). Thus, while the ’208 Specification (| 139) states that “the vagus nerve may be stimulated either mechanically or electrically in a low-intensity and low duty-cycle fashion without desensitizing the vagus nerve or its targets,” claim 1 is not limited to a low-duty cycle and thus the argument is not commensurate in scope with the claim. Unexpected results must be “commensurate in scope with the degree of protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005). In other words, Appellants argue that certain stimulation parameters achieve stimulation without desensitization, but claim 1 is not limited to these conditions. Moreover, with respect to dependent claim 3, which has a signal on- time from 1 to 120 seconds (i.e., a recited duty-cycle), Appellants have not 10 Appeal 2016-008350 Application 11/318,075 guided us to a definition of “low duty” that defines it to be same range as claimed. Consequently, even if the low-duty, low-intensity, or the low duty cycle alone, regimens achieve unexpected results, Appellants have not established that these parameters correspond to those recited in claim 3. Furthermore, Appellants have not provided objective evidence to substantiate their assertion of unexpected results. An applicant cannot prove unexpected results with attorney argument and bare statements without objective evidentiary support. See In re Lindner, 59 C.C.P.A. 920, 457 F.2d 506, 508 (CCPA 1972); In re Geisler, 116 F.3d 1465 (Fed. Cir. 1997) (“attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness”); In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995) (“It is well settled that unexpected results must be established by factual evidence. Mere argument or conclusory statements ... [do] not suffice.”) (quoting In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)). CFMT, Inc. v. Yieldup Inti Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003). For example, while unexpected results and criticality is asserted, Appellants have not provided evidence that ranges outside the claimed range do not achieve these results, such as voltages outside 0.01—1 Volts (claim 1) and values outside the recited on-time of 120 seconds (claim 3). Appellants have not even provided evidence that an on-time over the entire claimed range of claim 3, such as 1 second, and at the recited voltage range of claim 1, would achieve the claimed therapeutic effect and asserted results stated in paragraphs 138 and 139 of the ’208 Specification, such as avoiding desensitizing the vagus nerve. Appellants reproduced Figure 5 from the Specification as evidence that “[stimulation within the claimed ranges results in a low duty cycle stimulation, i.e. a stimulation with a relatively short signal on-time, to 11 Appeal 2016-008350 Application 11/318,075 generate a long lasting reduction in inflammation.” Reply Br. 3. Appellants did not identify the stimulation parameters used to generate the information provided in Figure 5. Nonetheless, it appears from Example 2 of the ’075 Specification that the figure was generated from “electrical stimulation for 30 sec (1mA, 0.5ms, 30Hz).” ’075 Spec. 21:19-26. Appellants did not establish that these parameters met the claimed signal voltage of 0.01 Volt to 1 volt recited in claim 1. Thus, the results in Figure 5 are not probative of unexpected results and non-obviousness for claim 1. As to claim 3, in addition to Appellants’ failure to establish that the voltage used to generate the data in Figure 5 falls within the scope of the claim, Appellants have also not established that all parameters within the scope of the claim would produce the data said to be unexpected for the single set of conditions described in Example 2 of the ’075 Specification and that stimulation conditions outside this range, such as those of Boveja or Tracey, would not result in the stated therapeutic persistence. When unexpected results are proffered by an appellant to rebut a prima facie case of obviousness, the appellant must “provide[] an adequate basis to support the conclusion that other embodiments falling within the claim will behave in the same manner” in order to “establish that the evidence is commensurate with [the] scope of the claims.” In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011). One data point is insufficient “to ascertain a trend in the exemplified data which would allow [one having ordinary skill in the art] to reasonably extend the probative value thereof.” In re Kollman, 595 F.2d 48, 56 (Fed. Cir. 1979). Here, therefore, Appellants must demonstrate or explain why the result of the single tested set of 12 Appeal 2016-008350 Application 11/318,075 stimulation conditions would establish the asserted result for the full scope of claims 1 and 3. Inherency Appellants contend that the Examiner did not “establish that stimulation using the different parameter ranges of Boveja would necessarily result in a therapeutic effect that persists for greater than 2 hours after stimulation has ended.” Appeal Br. 7. This argument does not persuade us that the Examiner erred. Appellants contend that the patentability of the claimed subject matter rests on the result (“the therapeutic effect persists for at least 2 hours after stimulation has ended”) of specifically recited stimulation parameters which the Examiner found to be suggested by Boveja. Because the PTO has no facilities for determining whether the stimulation parameters described by Boveja would (or would not) produce the claimed result, the Examiner reasonably concluded, based on the identity of the overlap of the stimulation parameters between the claims and Boveja, that such parameters would produce the claimed persistent therapeutic effect. The Examiner’s position is sound and scientifically logical because producing a therapeutic effect that persists for 2 hours after stimulation has ended is a direct consequence of the only active step of claim 1 namely applying a signal voltage from 0.01 Volt to 1 Volt and Boveja expressly teaches pulse amplitude that overlaps with this range. Under these circumstances, it is well-established by precedent that the burden shifts to the applicant to prove the prior art, namely Boveja and Tracey, would not necessarily result in the claimed therapeutic result. In re Best, 562 F.2d 13 Appeal 2016-008350 Application 11/318,075 1252, 1254—55 (CCPA 1977). Applicants have not met this burden on the record before us. Appellants assert that the claimed range produces the recited therapeutic effect, but they did not show that values outside the range, as described in Boveja, would not. Appellants contend that the ranges in Boveja “encompass high duty- cycle stimulation” and that the Examiner has not established that stimulation “using the different parameter ranges of Boveja would necessarily result in a therapeutic effect that persists for greater than 2 hours after stimulation has ended.” Appeal Br. 7. As explained above, Appellants have the burden of showing that ranges outside those which are claimed do not exhibit the recited therapeutic persistence. Summary For the foregoing reasons, the rejection of claim 1 as obvious in view of Boveja, Tracey, and Shafer is affirmed. Claims 2—4, 34, 36, 38, and 39 were not argued separately and fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). REJECTION 2 Claims 5—7 recite a list of inflammatory conditions. The Examiner cited Tracey for teaching the treatment of myocardial ischemia or atherosclerosis — one of the specific conditions listed in claims 5—7 using vagus nerve stimulation. Ans. 4. Appellants make the same argument for claims 5—7 that they did for claim 1. Consequently, we affirm the rejection of claims 5—7 for the same reasons. 14 Appeal 2016-008350 Application 11/318,075 REJECTION 3 Dependent claims 8—12 recite positions where the vagus is stimulated. The Examiner cited Whitehurst as teaching the recited positions. Final Act. 4. Claims 35 and 37 recite measuring cytokine levels, which the Examiner also found described in Whitehurst. Id. at 5. Appellants make the same argument for claims 8—12 that they did for claim 1. Consequently, we affirm the rejection of claims 8—12 for the same reasons. TIME PERIOD 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)(iv). AFFIRMED 15 Copy with citationCopy as parenthetical citation