Ex Parte Clagett-Dame et alDownload PDFPatent Trial and Appeal BoardJan 20, 201612920540 (P.T.A.B. Jan. 20, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/920,540 09/01/2010 60961 7590 01/22/2016 Intellectual Property Dept/Dewitt Ross & Stevens Wisconsin Alumni Research Foundation 2 East Mifflin Street, Suite #600 Madison, WI 53703-2865 Margaret Clagett-Dame 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. 09820. 93 7 /P08240US02 5865 EXAMINER GALISTEO GONZALEZ, ANTONIO ART UNIT PAPER NUMBER 1636 NOTIFICATION DATE DELIVERY MODE 01122/2016 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): docket-ip@dewittross.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte MARGARET CLAGETT-DAME, HECTOR F. DELUCA, NIRCA J. NIEVES, and KATARZYNA BARYCKA Appeal2013-006834 Application 12/920,540 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and JOHN G. NEW, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal 1 under 35 U.S.C. § 134 involving claims to an oral dosage form composition. The Examiner rejected the claims on grounds of improper dependent form and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellants identify the Real Party in Interest as the Wisconsin Research Alumni Foundation (see App. Br. 2). Appeal2013-006834 Application 12/920,540 Statement of the Case Background "Retinoids are natural and synthetic compounds that are structurally related to vitamin A. All-trans retinol is the major circulating form of vitamin A. It is oxidized in the body to all-trans retinaldehyde, which can be further oxidized to all-trans retinoic acid (atRA)" (Spec. i-f 5). "Various forms of atRA and various synthetic retinoids have been used to treat a number of skin conditions, including acne, psoriasis, ichthyosis, photoaging, wrinkling, age spots and cancer" (Spec. i-f 8). The Claims Claims 26, 27, 32, 33, 50, and 51 are on appeal. 2 Independent claim 26 is representative and reads as follows: 26. An oral dosage form composition comprising: a therapeutically effective dose of an active pharmaceutical ingredient selected from the group consisting of: and 0 0 J\l o~~ in combination with a pharmaceutically suitable oral carrier system. 2 Claims 30, 36, 38, 39, 42, 44, 45, 48, 52, and 53 were withdrawn from prosecution (see Appeal Br., Claims Appendix). 2 Appeal2013-006834 Application I2/920,540 The Issues A. The Examiner rejected claims 27 and 33 under 35 U.S.C. § I I2, fourth paragraph as being of improper dependent form for failing to limit the subject matter of the previous claim (Ans. 5). B. The Examiner rejected claims 26, 27, 32, 33, 50, and 5I under 35 U.S.C. § I03(a) as obvious over Pokrovskaya3 and DeLuca4 (Ans. 6-8). A. 35 U.S.C. § 112,fourth paragraph The Examiner finds that "the subject matter of claims 26 and 32 is an active pharmaceutical ingredient comprising all-trans-retinoic acid iso-butyl ester. Claims 27 and 33 fail to further limit the claims from which they depend" (Ans. 5). Appellants contend that"[ c ]laims 27 and 33 each recite that the active pharmaceutical ingredient is IB-RA and therefore limit the subject matter of their respective parent claims" (App. Br. IO). We find that Appellants have the better position. Claims 26 and 32 are drawn to an oral dosage form comprising either IB-RA or IA-RA (see Spec. i-f 72), while claims 27 and 33 are limited to IB-RA. Therefore, claims 27 and 33 further limit claims 26 and 32 by not encompassing oral dosage forms with IA-RA, and therefore satisfy the requirements of 35 U.S.C. § 112, fourth paragraph. 3 Pokrovskaya et al., Effect of Isobutyl Ester of Retinoic Acid on the Cellular Composition of Bronchoalveolar Lavage and on the Mitotic Activity of Alveolar Monocyte-Macrophages in Rats, I I 8 BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE I337-I339 (1994). 4 DeLuca et al., US 7,I26,0I 7 B2, issued Oct. 24, 2006. 3 Appeal2013-006834 Application 12/920,540 B. 35 US. C. § 103 (a) over Pokrovskaya and DeLuca The Examiner finds that Pokrovskaya teaches "a parenteral dosage composition comprising a therapeutically effective dose of an active pharmaceutically ingredient comprising all-trans-retinoic acid iso-butyl ester and a pharmaceutically suitable parenteral carrier" (Ans. 6). The Examiner acknowledges that Pokrovskaya does not teach "wherein the dosage form is an oral dosage form ... or a topical dosage form with a pharmaceutically suitable topical carrier" (Ans. 6). The Examiner finds that DeLuca teaches "oral and topical dosage compositions comprising a therapeutically effective dose of an alkyl ester of all-trans-retinoic acid and [ ] oral or topical pharmaceutically suitable carriers" (Ans. 7). The Examiner finds it obvious to "have the active ingredient of Pokrovskaya et al. and prepare the ingredient in oral or topical dosage forms ... because the substitution of one known carrier system for another would have yielded predictable results to one of ordinary skill in the art" (Ans. 7- 8). The issue with respect to this rejection is: Does the evidence of record support the Examiner's conclusion that Pokrovskaya and DeLuca render obvious oral or topical compositions of the retinoic acids required by claims 26 and 32? Findings of Fact 1. Pokrovskaya teaches that "IERA was administered intraperitoneally daily for two weeks at doses of 1, 10, and 100 mg/kg body weight in 0.5 ml soybean oil" (Pokrovskaya 1337, col. 2). 4 Appeal2013-006834 Application 12/920,540 2. Pokrovskaya teaches "IERA in a dose of 1 mg/kg stimulated proliferation of the cells of the macrophagal series in the alveoli, while a dose of 10 mg/kg had a protective anti-inflammatory effect which was manifested by the absence of inflammatory lung pathology in all experimental animals" (Pokrovskaya 1339, col. 2). 3. Deluca teaches that "[a]s is well known, the modified retinoid compounds may be present in a pharmaceutical composition to treat and/or prevent the previously mentioned diseases and disorders in a pharmaceutically effective amount" (DeLuca, col. 19, 11. 22-25). 4. DeLuca teaches that the "modified retinoid compounds may be administered topically, transdermally, orally or parenterally, and typical oral dosages are from about 5 mg/day to about 5 g/day. The proportion of each of the compounds in the composition is dependent upon the particular disease state being addressed and the degree of activity desired" (DeLuca, col. 19, 11. 29-34). 5. De Luca teaches that the specific dosage administered in any given case will be adjusted in accordance with the specific compounds being administered, the disease to be treated, the condition of the subject and the other relevant medical facts that may modify the activity of the drug or the response of the subject as is well known by those skilled in the art. (DeLuca, col. 19, 11. 39-44). 6. DeLuca teaches "modified retinoid compounds that exhibit a desirable and highly advantageous pattern of biological activity in vivo, namely, the more gradual onset and more prolonged duration of activity relating to cell proliferation" (DeLuca, col. 2, 11. 20-24). 5 Appeal2013-006834 Application 12/920,540 7. DeLuca teaches a tert-butyl retinoic acid as shown below: (DeLuca, col. 8, 1. 60). 8. The Specification teaches that the "oral formulation was made by mixing each API with Wesson® soybean oil" (Spec. i-f 79). 9. The Specification teaches "[p ]reparation of oral retinoid dosing formulations. A concentrated stock solution containing each retinoid was prepared in dichloromethane. . . . The purity of the ... IB-RA ... was determined ... [a] predetermined volume of retinoid-containing solution was added to Wesson® oil, the sample was mixed, and the residual dichloromethane was removed" (Spec. i-f 82). 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). "It is well settled that 'anticipation is the epitome of obviousness."' In re McDaniel, 293 F.3d 1379, 1385 (Fed. Cir. 2002). Analysis Claim 26 is drawn to an oral dosage form comprising an isobutyl ester of retinoic acid and a "pharmaceutically suitable oral carrier system." Claim 32 is drawn to the same composition with the term "topical" replacing "oral." The Specification exemplifies an oral dosage form comprising an 6 Appeal2013-006834 Application 12/920,540 isobutyl ester of retinoic acid with soybean oil as the suitable oral carrier (FF 8-9). Pokrovskaya teaches a dosage form comprising an isobutyl ester of retinoic acid combined with soybean oil as the carrier (FF 1 ). The evidence therefore supports a finding that Pokrovskaya's dosage form is identical in structure to the compositions required by claims 26 and 32, because "[p ]roducts of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990), Pokrovskaya's dosage form anticipates claims 26 and 32, necessarily rendering claims 26 and 32 obvious. McDaniel, 293 F.3d at 1385. Moreover, in the absence of specific structural limitations distinguishing the intended use of "oral" or "topical" dosage relative to Pokrovskaya's intraperitoneal dosage, the "mere statement of a new use for an otherwise old or obvious composition cannot render a claim to the composition patentable." In re Zierden, 411 F.2d 1325, 1328 (CCPA 1969). We recognize that the Examiner relies upon DeLuca because the Examiner finds that "Pokrovskaya et al. lack the dosage form wherein the dosage form is an oral dosage form with a pharmaceutically suitable oral carrier or a topical dosage form with a pharmaceutically suitable topical carrier" (Ans. 6). While we do not interpret the "oral" or "topical" dosage form as structurally distinguishing the composition of Pokrovskaya from those of claims 26 or 32, we agree with the Examiner that if the terms "oral" or "topical" were interpreted as imposing a structural limitation on claims 26 7 Appeal2013-006834 Application 12/920,540 and 32, the combination of Pokrovskaya and DeLuca would still render claims 26 and 32 obvious. DeLuca teaches treatment with retinoids (FF 3) and specifically teaches that modified retinoid compounds can be administered topically or orally, as well as parenterally (FF 4). We agree with the Examiner that: it would have been obvious to a person of ordinary skill in the art at the time of the invention to have the active ingredient of Pokrovskaya et al. and prepare the ingredient in oral or topical dosage forms. A person of ordinary skill in the art would be motivated to do so to provide a systemic delivery system without the inconvenience of injections, as an oral dosage allows; or to provide a localized delivery system that overcomes the side or toxic effects systemic delivery may carry, as a topical dosage allows. (Ans. 7). We further agree that the "substitution of one known carrier system for another \VOUld have yielded predictable results" (i~JlS. 8). Appellants "submit that the present rejection is improper because there is no evidence of record to suggest that the combination of elements proposed by the Office would have worked for its 'intended purpose"' (App. Br. 4 ). Appellants specifically contend that "there is no evidence of record to suggest that a combination of the isobutyl ester of retinoic acid (IERA) of Pokrovskaya et al. (the alleged all-trans-retinoic acid isobutyl ester) with the pharmaceutically suitable oral or topical carrier systems of DeLuca et al. would have been effective in performing any of the known functions of IERA" (App. Br. 5). We are not persuaded. Both Pokrovskaya and DeLuca are drawn to administration of retinoic acid compounds (FF 1---6) and DeLuca specifically 8 Appeal2013-006834 Application 12/920,540 teaches that a variety of different routes will function for the administration of retinoic acid compounds (FF 4). DeLuca's teaching provides evidentiary support for the Examiner's position, providing a prima face case. Kubin stated that "[ r ]esponding to concerns about uncertainty in the prior art influencing the purported success of the claimed combination, this court [in 0 'Farrell] stated: ' [ o ]bviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success."' In re Kubin, 561F.3d1351, 1360 (Fed. Cir. 2009) (citing In re O'Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988). Appellants contend that in Pokrovskaya, the "anti-inflammatory effects in the lung were observed only with injection of 10 mg/kg IERA. None of the other tested doses of IERA, including 1 mg/kg and 100 mg/kg, produced such effects" (App. Br. 6). Appellants contend that "unpredictability of providing such effects of IERA at the various injected doses indicates that predictability of providing the effects with different compositional forms is far from a given" (App. Br. 6). We find this argument unpersuasive because the art is replete with evidence that optimization of dosing is required to obtain a desired effect. While Pokrovskaya recognizes that "[ d]ifferent doses of IERA were found to exert different biological effects on the animals" (Pokrovskaya 133 8, col. 1 ), DeLuca explains that "the specific dosage administered in any given case will be adjusted in accordance with the specific compounds being administered, the disease to be treated, the condition of the subject and the other relevant medical facts" (FF 5). DeLuca's express recognition that dosing using retinoic acids is optimizable based on a variety of variables 9 Appeal2013-006834 Application 12/920,540 supports the Examiner's finding of a reasonable expectation of success in either orally or topically administering Pokrovskaya's composition. Appellants contend that the cited prior art collectively fails to teach or suggest oral or topical formulations of any compound, including IERA, as being suitable for carrying out any effects in the lung. There is therefore no reason for a practitioner in the art to make the proposed combination of elements, i.e., providing a topical or oral compositional form comprising a combination of IERA with the pharmaceutically suitable oral and topical carrier systems of DeLuca et al. for increasing mitotic activity of cells of the macrophagal series in alveoli and inducing an anti-inflammatory effect in the lung. (App. Br. 7). We find this argument unpersuasive because Pokrovskaya's mode of IERA delivery was not directly to the lung, but rather was intraperitoneal (FF 1 ). Whether the drug is administered intraperitoneally, orally, or topically, we agree with the Examiner that "once the compound enters the body it will also go into the vascular system, which will deliver the compound throughout the body, including the lungs" (Ans. 17). Moreover, DeLuca teaches that the "modified retinoid compounds may be administered topically, transdermally, orally or parenterally" (FF 4), further supporting the Examiner's reasoning that alternative delivery modes would have been obvious equivalents in the absence of any unexpected results for the oral or topical composition. Appellants contend that "neither Pokrovskaya et al. nor DeLuca et al. provides teachings relevant to an entire genus of compounds having the breadth of 'alkyl esters of all-trans-retinoic acid"' (App. Br. 8). 10 Appeal2013-006834 Application 12/920,540 We find this argument unpersuasive because Pokrovskaya expressly teaches the IERA compound in the suitable carrier system of soybean oil (FF 1) as required by claims 26 and 32, and DeLuca teaches that retinoic acid compounds may be administered topically and orally (FF 4 ). In addition, we note that the structures of Pokrovskaya's IERA compound and DeLuca's tert butyl retinoic acid compound share very close structural and chemical similarity as shown in comparison below: Isobutyl ester of retinoic acid (IERA) )l I,,. ~. 'oA Tert butyl ester of retinoic acid For obviousness, "'it is sufficient to show that the claimed and prior art compounds possess a 'sufficiently close relationship ... to create an expectation,' in light of the totality of the prior art, that the new compound will have 'similar properties' to the old."' Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1293 (Fed. Cir. 2012). Here, where the prior art of Pokrovskaya specifically teaches the claimed compound, the only issue is whether formulating that known compound in a different dosage form, such as the oral or topical forms taught by DeLuca for a very similar compound, would have been obvious. 11 Appeal2013-006834 Application 12/920,540 We conclude that based on the teachings of Pokrovskaya and DeLuca, there was a reasonable expectation that the properties would be sufficiently similar to suggest using Pokrovskaya's IERA in topical and oral formulations as taught by DeLuca (FFs 1, 4, 7). Appellants contend that "neither Pokrovskaya et al. nor DeLuca et al. provides any teachings to suggest that a topical, localized delivery system that avoids side effects resulting from systemic delivery would be capable of eliciting any effects in the lung" (App. Br. 10). Appellants contend that "[i]fIERA or a hydrolyzed product thereof were to be delivered to the lungs via the vascular system in amounts effective amounts to carry out the taught effects in the lung, it is not evident that the motivation of overcoming toxic side effects of systemic delivery would predictably be realized" (Reply Br. 2). We find these arguments unpersuasive because there are no limitations in claims 26 and 32 that require avoidance of side effects. See In re Self, 671F.2d1344, 1348 (CCPA 1982) ("[A]ppellant's arguments fail from the outset because ... they are not based on limitations appearing in the claims.") In addition, DeLuca teaches the use of "relevant medical facts that may modify ... the response of the subject, as is well known by those skilled in the art" (FF 5), teaching that the ordinary artisan would have been able to balance the risks of side effects with the benefits of treatment. Conclusion of Law The evidence of record supports the Examiner's conclusion that Pokrovskaya and DeLuca render obvious oral or topical compositions of the retinoic acids required by claims 26 and 32. 12 Appeal2013-006834 Application 12/920,540 SUMMARY In summary, we reverse the rejection of claims 27 and 33 under 35 U.S.C. § 112, fourth paragraph as being of improper dependent form for failing to limit the subject matter of the previous claim. We affirm the rejection of claims 26 and 32 under 35 U.S.C. § 103(a) as obvious over Pokrovskaya and DeLuca. Claims 27, 33, 50, and 51 fall with claims 26 and 32. 37 C.F.R. § 41.37(c)(iv). No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED cdc 13 Copy with citationCopy as parenthetical citation