Ex Parte DDownload PDFPatent Trial and Appeal BoardJun 29, 201613680452 (P.T.A.B. Jun. 29, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/680,452 11/19/2012 26231 7590 07/01/2016 FISH & RICHARDSON P.C. (DA) P.O. BOX 1022 MINNEAPOLIS, MN 55440-1022 FIRST NAMED INVENTOR Josephine S. D'Alessandro 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. 14131-0102001 1157 EXAMINER BOWERS, ERIN M ART UNIT PAPER NUMBER 1653 NOTIFICATION DATE DELIVERY MODE 07/01/2016 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): P ATDOCTC@fr.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JOSEPHINE S. D' ALESSANDR0 1 Appeal2014--005743 Application 13/680,452 Technology Center 1600 Before DEMETRA J. MILLS, ERIC B. GRIMES, and JOHN E. SCHNEIDER, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to assays for predicting the efficacy of amino acid copolymers which have been rejected for obvious-type double patenting and as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm. STATEMENT OF THE CASE Glatiramer acetate is the active ingredient in COP AXONE®, which is marketed for treatment of multiple sclerosis. Spec. i-f 4. "[G]latiramer 1 Appellant identifies the real party-in-interest as Momenta Pharmaceuticals, Inc. Appeal Br. 2. Appeal2014-005743 Application 13/680,452 acetate (GA) consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids." Id. The invention relates to a cell based assay for determining the level of GA present in a batch of composition containing GA to determine if the composition should be formulated as a drug product. Appeal Br. 2. The assay uses GA-specific Th2 cells which can reproducibly distinguish GA from other amino acid copolymers. Id. Claims 1-3, 5-12 and 14--22 are on appeal. Claims 1 and 21 are illustrative and read as follows: 1. A method comprising: incubating at least one sample of a batch of a composition comprising glatiramer acetate (GA) in the presence of antigen- presenting cells ( APCs) and a population of cells comprising polyclonal GA-specific type 2 T helper (Th2) cell, wherein the population of cells has less than 1 % cross-reactivity with myelin basic protein (MBP); determining the level of at least one GA-induced polypeptide expressed by the population of cells at a predetermined time point; and formulating at least a portion of the batch as a drug product if the level of the at least one GA-induced polypeptide is within a predetermined range. 21. A method comprising: incubating at least one sample of a batch of a composition comprising GA in the presence of APCs and a population of cells comprising polyclonal GA-specific Th2 cells, wherein the population of cells has less than 1 % cross-reactivity with MBP and, when incubated for 24 hours at a concentration of 1x106 cells/ml in the presence of APCs and at least 15 µg/ml GA, produces at least 100-fold more IL-4 than when incubated in the presence of APCs and MBP; 2 Appeal2014-005743 Application 13/680,452 determining the level of at least one GA-induced polypeptide expressed by the population of cells at a predetermined time point; and formulating at least a portion of the batch as a drug product if the level of the at least one GA-induced polypeptide is within a predetermined range. The claims stand rejected as follows: Claims 1-3, 5-12 and 14--22 have been rejected for obviousness-type double patenting over claims 101, 102, 105, 107 and 109 of co-pending Application No. 12/665,794 filed Nov. 15, 2012 by D' Alessandro ("'794 Application") in view of Klinger, US 7,429,374 B2 (issued Sept. 30, 2008) ("Klinger"), Neuhaus, et al., Multiple sclerosis: Comparison of copolymer- 1-reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper l to T helper 2 cells, 97 PROC. NAT'L ACAD. SCI. USA 7452 (2000) ("Neuhaus"), and Chen at al., Glatiramer acetate induces Th2- biased response and crossreactivity with myelin basic protein in patients with MS, 7 MULTIPLE SCLEROSIS 209 (2001) ("Chen"). 2 Claims 1-3, 5-12 and 14--22 have been rejected under 35 U.S.C. § 103 as obvious over D' Alessandro, WO 2008/157697 A2 (published Dec. 24, 2008) ("D'Alessandro) in view of Klinger, Neuhaus and Chen. 2 Appellant has offered no separate argument for the obviousness-type double patenting rejection, but instead requests that we consider the arguments concerning the Section 103 rejection as applicable to the obviousness-type double patenting rejection. We shall therefore address the Section 103 rejection first and then tum to the obviousness-type double patenting rejection. 3 Appeal2014-005743 Application 13/680,452 Issue I In rejecting the present claims as obvious, the Examiner finds that D 'Alessandro teaches a method for evaluating agents such as GA for suitability for a pharmaceutical preparation using a cell capable of cytokine induced protein expression. Final Action 17. The Examiner finds that the cells are incubated with an amino acid copolymer such as GA for a period of time. Id. The Examiner goes on to find that the level of the secreted proteins is then measured and compared to reference values. Id. The Examiner finds that Klinger teaches a process for measuring the relative potency of GA using lymph cells from mice immunized with GA. Final Action 19. The Examiner finds that the cells are then incubated with an amount of GA and the amount of cytokine produced is then measured. Id. The Examiner also finds that the GA-specific ThO cells do not respond to human MBP or analogs ofMBP. Id. at 20. With respect to Neuhaus, the Examiner finds that Neuhaus discloses that GA-reactive Th2 cells from Multiple Sclerosis ("MS") patients treated with GA exhibit a Th2 response. Final Action 20. The Examiner finds that the Th2 cells, when incubated with GA, produce ~30 pg/ml ofIL-4 and when incubated with MBP produced ~6pg/ml of IL-4. The Examiner finds that the Th2 cells of Neuhaus would inherently be polyclonal. Id. Turning to Chen, the Examiner finds that Chen teaches the isolation of GA specific Th2 cells from MS patients. Final Action 21. The Examiner finds the Chen teaches that after two stimulation cycles the Th2 cells did not react with MBP or an MPB analog. Id. The Examiner also finds that the Th2 cells described in Chen are inherently polyclonal. Id. 4 Appeal2014-005743 Application 13/680,452 The Examiner concludes by finding that "it would have been obvious to one of ordinary skill in the art to combine the GA production, screening, and drug formulation method of '794 with the specific and sensitive GA potency screening method of Klinger because Klinger's improvements would impart greater sensitivity to the screening portion of the '794 method." Final Action 21. The Examiner goes on to find that "it would have been obvious to one of ordinary skill in the art to use the GA-reactive Th2 cells of Neuhaus in the GA production/screening/drug formulation method of Klinger and '794 because Klinger teaches that the method can be adapted to standardize other T cell antigens for use in pharmaceutical compositions (column 30, lines 14--15). The cells ofNeuhaus are functionally equivalent to the cells of Klinger, i.e., both the cells of Neuhaus and the cells of Klinger are T cells that specifically produce cytokines in response to stimulation with GA" Final Action 22. The Examiner also finds that "[i]t would have been obvious to one of ordinary skill in the art to utilize Th2 cells that do not cross-react with MBP, as taught by Chen, because Klinger teaches that the lack of cross-reactivity with MBP indicates that the method was very specific to GA peptides and was sensitive to the average MW of the peptide mixture (column 30, lines 4--9)." Final Action 23. Appellant contends that the Examiner has failed to establish a prima facie case of obviousness. Appeal Br. 5. Appellant contends that Klinger does not teach that T cells other than the ThO cells used in Klinger can be used in his method. Id. Appellant also contends that one skilled in the art would not have a reasonable expectation of success in substituting the Th2 cells of Chen or Neuhaus for the ThO cells of Klinger as the different T cells 5 Appeal2014-005743 Application 13/680,452 are from different sources and are not functionally equivalent. Appeal Br. 6-7, Reply Br. 8-10. With respect to claim 21, Appellant argues that Chen does not disclose the 100-fold increase in IL-4 production exhibited by the Th2 cells when incubated with APC and GA when compared to IL-4 production when the cell are incubated with APCs and MPB. Appeal Br. 8-10, Reply Br. 10- 11. Appellant also argues that the lack of proliferation of Th2 cells in Chen when exposed to MBP does not mean that there is no IL-4 production. Appeal Br. 8-10, Reply Br. 10-11. The issue with respect to this rejection is whether the Examiner has established by a preponderance of the evidence that the rejected claims are obvious over D' Alessandro combined with Klinger, Neuhaus and Chen as defined by 35 U.S.C. § 103(a). Findings of Fact FF 1. D 'Alessandro teaches a method for evaluating the properties of GA. D 'Alessandro 1. FF2. The method ofD' Alessandro comprises the steps of (a) providing at least one cell that is capable of a expressing protein that is induced by a cytokine; (b) contacting the at least one cell with an amount of the amino acid copolymer and the cytokine at a concentration and for a period of time sufficient to induce the cell to express the induced protein; ( c) measuring the expression, secretion, induction, presence or level of the induced proteins; and ( d) comparing the measured expression, secretion, induction, presence or level of the induced protein to a reference value, a cytokine induction profile or a pharmaceutical specification for a market pharmaceutical preparation of 6 Appeal2014-005743 Application 13/680,452 glatiramer acetate to evaluate a property of the ammo acid copolymer. D' Alessandro 2. FF3. Klinger discloses a method for measuring the potency of a batch of GA relative to the potency of a known reference batch. Klinger col. 2, 11. 17-20. FF4. The method of Klinger comprises (a) isolating lymph cells from mice immunized with an amount of a reference batch of glatiramer acetate, (b) incubating the cells with an amount of a test batch of glatiramer acetate, ( c) determining the amount of a cytokine produced after 18- 21 hours of incubation and ( d) correlating the level of cytokine produced by the cells incubated with the reference glatiramer acetate with the level produced by cells incubated with the test glatiramer acetate so as to determine the potency of the test batch of glatiramer acetate. Klinger coL 2; L 53---coL 3; L 20. FF5. The T cells used by Klinger do not cross react with human MBP or two analogs of MBP. Klinger col. 26, 11. 34--49. FF6. Neuhaus discloses the isolation of Th2 cells which produce IL- 4 when incubated with GA. Neuhaus 7453-56. FF7. Chen discloses Th2 cells which are GA-specific. Chen, entire document. FF8. The Th2 cells disclosed in Chen do not react with MBP or an MPB analog after two stimulation cycles. Chen 213. 7 Appeal2014-005743 Application 13/680,452 Principles of Law "The factual predicates underlying an obviousness determination include the scope and content of the prior art, the differences between the prior art and the claimed invention, and the level of ordinary skill in the art." In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998). "[I]nterrelated teachings of multiple patents; the effects of demands known to the design community or present in the marketplace; and the background knowledge possessed by a person having ordinary skill in the art, all [can provide] an apparent reason to combine the known elements in the fashion claimed." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) Combining references can be based on common sense as long as the reasoning is explained sufficiently. See Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324, 1328-29 (Fed. Cir. 2009). "Where ... the claimed and prior art products are identical or substantially identical ... 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. ... [The] fairness [of the burden-shifting] 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). Analysis Claim 1 is representative of the rejected claims and recites a method for determining the amount of GA present in a batch. We agree with the Examiner that claim 1 would have been obvious to one skilled in the art at the time the invention was made. D 'Alessandro teaches a method for 8 Appeal2014-005743 Application 13/680,452 evaluating the properties of a polymer such as GA using a cell line. Klinger teaches a method for assaying the potency of a batch of GA using ThO cells. FF3--4. The ThO cells of Klinger have little or no cross reactivity with MBP. FF5. Neuhaus disclosed the isolation of Th2 cells which react with GA. FF6. Chen similarly discloses GA-specific Th2 cells and further teaches that the Th2 cells do not cross-react with MBP. FF 7-8. We agree with the Examiner that it would have been obvious to one skilled in the art to combine the method of D' Alessandro with the method of Klinger, because Klinger teaches that its method "provides the standardization of the measurement of the potency of GA," which "is essential in order to show batch to batch reproducibility with regards to potency." Klinger col. 6, 11. 27-32. It would have been a simple substitution to use the Th2 cells of Neuhaus or Chen in the combined assay method of D' Alessandro and Klinger. Appellant argues that the Examiner has failed to provide a motivation to combine the references. Appeal Br. 5. Appellant argues that Klinger teaches that his method can be used with other antigens and not other T cell types. Id. We are unpersuaded. As the Examiner has found, the Th2 cells of Neuhaus and Chen are functionally equivalent in that they all secrete cytokines in response to stimulation with GA. Ans. 39. The proposed substitution would have been routine for one skilled in the art. Appellant next argues that the Th2 cells of Neuhaus and Chen are not functionally equivalent to the ThO cells of Klinger. Appeal Br. 6-7, Reply Br. 8-10. Appellant argues that the Th2 cells of Chen and Neuhaus represent a less diverse population of cells than the ThO cells used in Klinger and would not detect the many different epitopes present in GA nor would 9 Appeal2014-005743 Application 13/680,452 they be sensitive to the average molecular weight of GA. Appeal Br. 6-7. Again, we are not persuaded. The prior art of record shows that the T cells of Chen, Neuhaus and Klinger all share the same characteristics recited in claim 1: cytokine release in response to GA stimulation and lack of cross reactivity with myelin basic protein. FF6-8. Moreover, the detection of different epitopes and molecular weight are not recited in claim 1. With respect to claim 21, Appellant argues that the references do not disclose Th2 cells that have the ability to produce 100 fold more IL-4 when incubated with APCs and GA than when incubated with APCs and MBP. Appeal Br. 8-10. Appellant contends that Chen is silent with respect to cytokine production and that the Examiner improperly assumes that if there is no proliferation in response to MBP there is no cytokine production. Id. We are unpersuaded. We agree with the Examiner (Ans. 44) that the evidence is sufficient to shift the burden of showing that the Th2 cells of Chen do not possess the properties recited in claim 21. That is, Chen discloses Th2 cells that react with GA but not with MBP. FF7, FF8. The evidence supports the Examiner's position that producing IL-4 is characteristic of Th2 cells. See Neuhaus, abstract ("[T]he majority of [GA]- reactive TCL from [GA ]-treated patients predominantly ... produced IL-4--- i.e., were TH2.") 7456, right-hand col. ("[W]e selected one prototypical THI cytokine (IFN-y) and one TH2 cytokine (IL-4)."). Thus, one of skill in the art would expect that Chen's cells would produce IL-4 when contacted with GA but not with MBP. As the Examiner pointed out, the Patent Office is not equipped to make and test the cells of Chen, therefore the burden of establishing that the T cells of Chen do not possess the inherent properties shift to the Appellant. In re Best, 562 F.2d at 1255. 10 Appeal2014-005743 Application 13/680,452 Appellant argues that Chen's teaching about the lack of proliferation in response to MBP is not indicative of a lack of cytokine production as the proliferation of T cells and cytokine production may have been decoupled by the MBP. Reply Br. 9--10. We are unpersuaded. While the Bueno3 article cited by Appellant discloses that some partial agonists induce some effector responses and not others (e.g., production of IL-4 but no proliferation), Bueno also teaches that the "differences between partial agonists are quantitative and thus difficult to predict." Bueno 3502. Bueno used a modified fragment of MBP (peptides 68-86), Bueno 3497, whereas Chen used a different unmodified fragment (peptides 83-99) as well as the entire MBP protein, Chen 211. Appellant has offered no evidence that the modified fragment used in Bueno would induce the same reaction as MBP or the fragment used by Chen. Conclusion of Law We conclude that the Examiner has established by a preponderance of the evidence that claims 1 and 21 would have been obvious over D' Alessandro combined with Klinger, Neuhaus and Chen as defined by 35 U.S.C. § 103(a). Claims 2-3, 5-12 and 14--20 and 22 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). 3 Bueno, et al., Mechanism of modulation ofT cell responses by N- palmitoylated peptides, 34 EUR. J. IMMUNOL. 3497 (2004). 11 Appeal2014-005743 Application 13/680,452 II The Examiner also rejected the pending claims for obviousness-type double patenting over the co-pending '794 application in view of Klinger, Neuhaus and Chen. Appellant responded to this rejection by stating that the same arguments raised in connection with the Section 103 rejection are applicable to the obviousness-type double patenting rejection. Having found Appellant's arguments unpersuasive with respect to the section 103 rejection we find them unpersuasive here. We therefore affirm the obviousness-type double patenting rejection. SUMMARY We affirm the rejection claims 1-3, 5-12 and 14--22. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § l .136(a). AFFIRMED 12 Copy with citationCopy as parenthetical citation