DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
2. Applicant's submission filed on August 22, 2025 has been reviewed by the examiner and entered of record in the file.
3. No claim is amended, canceled, or added. Claims 1, 6 and 7 are under examination and are the subject of this office action.
Claim Rejections - 35 USC § 103
4. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
5. Claims 1, 6, and 7 remain rejected under 35 U.S.C. 103 as being unpatentable over Schlez et al., JEADV 2002 (cited on Applicant’s IDS of May 10, 2022), in view of Frolich and Bippi, U.S. Pat. No. 5,219,885, further in view of Gunji et al., Burns (1996), as evidenced by Zhi et al., Int J Clin Exp Med (2017).
Claim 1 is directed to a method for reducing the skin thickness and/or collagen deposition of an animal with scleroderma, comprising:
administering to the animal with scleroderma (more specifically, a human (claims 6 and 7)),
prostaglandin E1 methyl ester as the only active ingredient, wherein said PE1 methyl ester has a structure according to formula (I):
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6. Schlez et al. teach the administration of prostaglandin E1 ethyl ester to a human patient suffering from systemic scleroderma, wherein the administration successfully resolved skin lesions (see Abstract and “Discussion,” pages 527-528). Schlez et al. do not teach the administration of prostaglandin E1 methyl ester.
7. Yet, prostaglandin E1 methyl ester is a homolog of prostaglandin E1 ethyl ester, i.e., the only structural difference between the claimed and prior art compounds is the addition of a single -CH2- group. Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09. And, Frolich teaches that PGE1 prodrugs, in particular alkyl ester derivatives of Formula (I), (wherein the alkyl residue can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tertiary butyl), can be administered topically and avoid the disadvantages of PGE1 when administered arterially, intravenously or orally.
8. As such, one skilled in the art would be motivated to administer PGE1 methyl ester for the treatment of scleroderma in a human patient in need thereof, since one would have the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990).
9. Regarding the limitation of “reducing the skin thickness and/or collagen deposition” in the preamble, Gunji et al. teach that prostaglandin E1 (PGE1) decreased the degree of and/or prevented hypertrophic scarring in human patients, as measured by a reduction in the skin thickness of the scar (see page 399, right column, last paragraph- page 400, left column, first sentence, and Table 400). Gunji et al. suggest the use of topical PGE1 ointment to prevent excessive collagen synthesis (*it is noted that the previous Office Action cited page 403, left column, first paragraph, however, the proper citation is page 405, left column, first paragraph). And, it is clear as evidenced by Zhi et al. that excessive collagen deposition is implicated in the pathogenesis of hypertrophic scars (page 15221, abstract and right column, first paragraph).
10. As such, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to topically administer prostaglandin E1 methyl ester for the reduction of collagen deposition in a human patient in need thereof. One skilled in the art would have been motivated to administer prostaglandin E1 methyl ester, thereby reducing skin thickness in said patient, and would have had a reasonable expectation of success.
Thus, claims 1, 6 and 7 are prima facie obvious.
Response to Arguments
11. Applicant traverses the previous obviousness rejection over claims 1, 6 and 7, and argues the following points:
(i) Applicant argues that in Gunji, the specific mechanism by which PGE1 reduces scarring is unclear. Applicant argues that while Gunji teaches an in vitro study that may suggest PGE1 reduces collagen synthesis, one of skill in the art could not directly extrapolate in vitro experimental results to human treatment due to the differences between in vitro and in vivo microenvironments, i.e., “[i]t is well known to those skilled in the art that in vitro experimental results do not necessarily translate to therapeutic effects in vivo.” (Applicant’s Remarks, page 3). Applicant
contends that Gunji provides no experimental data or references and therefore lack evidentiary support, rendering the conclusion questionable.
12. Applicant's arguments have been fully considered but they are not persuasive. In response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The primary reference, Schlez et al., teaches the administration of prostaglandin E1 ethyl ester (the homolog of prostaglandin E1 methyl ester) to a human patient suffering from systemic scleroderma. Gunji is relied upon for suggesting that in vitro studies may demonstrate that an excess of collagen synthesis is prevented by PGE1 administration. Taken together, the combined prior art teaches suggests that a known homolog of PGE1 could be administered to animal with scleroderma, wherein said analog would reduce or prevent excessive collagen synthesis upon administration, with a reasonable expectation of success.
13. And, obviousness does not require absolute predictability. Conclusive proof of efficacy is not required to show a reasonable expectation of success. Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
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As guided by Gunji, one of skill in the art before the effective filing date of the claimed invention would have reasonably considered administering PGE1 to reduce or prevent excessive collagen synthesis in an animal, wherein the animal also has scleroderma.
(ii) Applicant submits two references, wherein “Evidence 1” suggests a correlation between wound healing time and the risk of scar formation. Applicant alleges that, “PGE1’s ability to accelerate wound healing through vasodilation alone may reduce the risk of scar formation, without necessarily involving the inhibition of collage deposition as suggested by the rejection.” (Applicant’s Remarks, Page 4).
(iii) The second reference, “Evidence 2,” describes the mechanism underlying trauma-induced hypertrophic scarring. Applicant argues that the pathological mechanisms of trauma-induced hypertrophic scarring is entirely distinct from systemic sclerosis, such that one of skill in the art “would not directly associate the treatment of traumatic scars with interventions for autoimmune diseases,” (Applicant’s Remarks, page 5, first paragraph). Applicant contends that, “the pathogenesis of scleroderma is complex, with different causes, and different treatment methods are adopted for scleroderma caused by different reasons.” (Applicant’s Remarks, page 6).
Applicant concludes that Gunji falls short of teaching features alleged by the examiner in the office action, “[a]s such, it appears that the Examiner is taking Official Notice of facts not on the record.” (Applicant’s Remarks, page 5).
14. Applicant's arguments have been fully considered but they are not persuasive. In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which Applicant relies, i.e., skin thickness and/or collagen deposition caused by/ as a result of systemic sclerosis, are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claim 1 is drawn to the mechanism of “reducing skin thickness and/or collagen deposition of an animal with scleroderma,” which is separate and distinct from a method of treating systemic scleroderma. Regarding the argument concerning the treatment of scleroderma and its pathogenesis, claim 1 is missing the recitation of “in need thereof,” i.e., as presently drafted, the claim reads on reducing the skin thickness and/or collage deposition in any animal that also has the comorbidity of scleroderma.
15. Regarding the teaching of Gunji and the examiner allegedly “taking Official Notice,” Gunji suggests the use of topical PGE1 ointment to prevent excessive collagen synthesis: “an excess of collagen synthesis might be shown by in vitro studies to be prevented by PGE1,” (page 405, left column, first paragraph). Thus, while the recited method of use is not explicitly taught by Gunji, it certainly motivates one of skill in the art to topically administer PGE1 to reduce or prevent collagen synthesis in the skin of an animal.
16. And, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." 27 F.3d at 554, 31 USPQ2d at 1132.). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Conclusion
17. Claims 1, 6 and 7 are pending in the application. Claims 1, 6 and 7 are rejected. No claim is presently allowable.
18. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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