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 .
Status of Claims
The response filed 10/8/26 has been considered. Claims 2, 16, 19, and 32 have been canceled in this reply. Claims 1, 6, 8, 9, 11, 13, 17, 18, 23, 25, 26, 28, 30, and 31 are pending and under examination on their merits.
Priority
This application claims benefit of provisional application 63/321,370, filed 3/18/22. As discussed below, the as-filed disclosure does not provide support for the claims as drafted because the written-description requirement is not met. As such, the effective filing date for prior-art purposes is 3/17/23, the date the parent PCT application was filed with WIPO.
Claim Objections
The objection to the claims is withdrawn in light of the amended claim listing.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 8, 9, 11, 13, 17, 18, 23, 25, 26, 28, 30, and 31 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a method that comprises contacting solid organ tissue with “an amount of a heparanase inhibitor effective to reduce transplant rejection of the tissue” after implantation. Claim 18 is drawn to a method for transplanting solid organ graft tissue comprising implanting the tissue, then contact it with “an amount of a heparanase inhibitor effective to reduce transplant rejection of the tissue.” Claims 1 and 18 list various heparanase inhibitors or “pharmaceutically acceptable salt[s]” of them. The skilled artisan would not have concluded that applicant possessed the claimed “effective amount” of these heparanase inhibitors.
Before the effective filing date, Ziolkowski et al. (2012, Journal of Clinical Investigation 122: 132-141) teaches the heparanase inhibitor PI-88 (sulfated phosphomannopentaose) is preventative for type 1 diabetes in NOD mice because it protects islets from radical oxygen species (ROS). (Page 135.) Cassinelli et al. (2020, “Non-Anticoagulant Heparins as Heparanase Inhibitors,” in Heparanase: From Basic Research to Clinical Applications, Vlodasky et al., eds.) reviews other applications for heparanase inhibitors. Cassinelli identifies heparanase inhibitors as useful antiviral agents (section 20.7.1 at page 511), anti-inflammatory agents (section 20.7.5 at page 513), and anti-cancer agents (section 20.7.3 at page 512). Barash et al. (2021, Cancers 13: 2959) teaches the heparanase inhibitor 4-MMI as useful for attenuating primary tumor growth and metastasis as well as for treating colitis, pancreatitis, diabetic neuropathy, tissue fibrosis, and viral infections involving heparanase. (Abstract.) Before the effective filing date, however, the art did not recognize a general role for heparanase inhibitors as being protective against transplant rejection when the compounds are contacted with tissue for transplantation. “[F]or inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.” MPEP 2163(II)(A)(3)(a)(1).
The skilled artisan would not have concluded that applicant possessed an effective amount of every heparanase inhibitor in claims 1 and 18 that would protect transplantable tissue from immune rejection upon implantation. Applicant provides a single working example in which rat lungs are placed on ex vivo lung perfusion (EVLP) for an undisclosed time with an unidentified amount of the agent heparostatin (SF4), then transplanted into recipients. (Paragraph 131.) Applicant observed reduced signs of transplant rejection compared to lungs not treated with SF4. (Paragraph 131.) The specification does not, however, provide sufficient disclosure such that the skilled artisan would identify an “effective amount” of SF4, much less an “effective amount” of every other heparanase inhibitor in claims 1 and 18.
Furthermore, claims 1 and 18 refer to administering “a therapeutic equivalent concentration to a concentration of heparastatin of at least 10 nM and no greater than 5 mM.” As discussed above, the specification does not identify the amount of SF4 that provides the desired outcome, so the skilled artisan would not have concluded that applicants possessed amounts of other heparanase inhibitors that are “therapeutic[ally] equivalent” to some concentration of SF4.
Response to Arguments
Applicant alleges that based on the teachings at pages 36-38 of provisional application 63/321,370 and Table A at page 34 of the as-filed specification, the skilled artisan would have known which heparanase inhibitors are useful in the invention and could have generated dose-response curves for each one. (Reply at 7-8.) The written-description requirement, however, is separate from the enablement requirement. “Conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description.” MPEP 2163(I) (quoting In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)). Undue experimentation may not have been required to determine which of the claimed compounds, and what concentration of each, have the required activity. That fact, however, does not convey that applicants possessed the invention as of the claims’ effective filing date. The data in the provisional application and Table A in fact show that the effects of different heparanase inhibitors are widely variant. This information, combined with the fact that the prior art recognized no role for heparanase inhibitors in preserving tissue for transplantation, demonstrates an unpredictability in the art that is not resolved by the showing in the as-filed application.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lora E Barnhart Driscoll whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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/Lora E Barnhart Driscoll/Primary Examiner, Art Unit 3991
