DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Applicant’s response (amendments and arguments) is acknowledged.
Claims 27-28, 31, 35-39, 42, 46-47 are pending after amendment and examined on the merits following the last response.
Any rejection no longer of record has been overcome by amendment/argument.
The examiner attempted to reach applicant’s representative (AR) via telephone to advance prosecution on the merits, but was unable to connect with AR. Notwithstanding, the examiner remains open to interview at any time.
The present application is the newest continuation in the present family, drawn to treating any nephropathy directly linked to increased levels of ET-1 compared to ET-1 levels in those without the nephropathy with the claimed ET-1 antagonists, wherein the following family patents have already issued or are pending over the following scope of treating various nephropathies with the same instantly claimed ET-1 antagonists: U.S. Patent No. 11,874,283 (IgA nephropathy); U.S. Patent No. 11,372,005 and 10,866,249 (both of varying scope to HIV-associated nephropathy (HIVAN); U.S. Patent No. 9,255,931 (focal segmental glomerulosclerosis (FSGS); and U.S. Patent Publication No. 20220260590 (glomerulonephritis), for which an obviousness double patenting rejection has been applied below.
Claim Rejections - 35 USC § 103 –
Obviousness, Modified, Necessitated by Amendment
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 – KSR Examples of ‘Rationales’ Supporting a Conclusion of Obviousness (Consistent with the “Functional Approach” of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 27-28, 31, 35-39, 42, and 46-47 remain/are rejected under 35 U.S.C. 103(a) as obvious over either Roden et al. (US20090054473) or KOPP, B., et al., "The role of Endothetin-l[ET-1] in the Pathogenesis of HIV-associated Nephropathy[HIVAN]", Journal of American Society of Nephrology, Vo1.19, pp.670A, SA-PO2496 (2008). (abstract only (illegible copy cited in the IDS of 4/24/12; see IDS note, bottom)); either alone based on that which was art-recognized about nephropathies as ET-1 associated (across conditions, e.g. diabetic and HIV; as for Kopp) and/or of the known ET-1 antagonists and what conditions they could treat (such as present ambrisentanm; nephropathies such as HIVAN or FSGS); or either in view of the other.
Roden teach the use of e.g. species ambrisentan (product/composition/kit) to treat a nephroathy (e.g. focused on diabetic nephropathy; however, any diabetic with HIV thereby part of the class being treated the nephropathy subspecies types FSGS or HIVAN); as well as diagnose nephropathy (art-recognized that elevated ET-1 levels indicative of some type of nephropathy as presently claimed in claim 9, based on teachings of Roden) (see entire document):
[0002] The present invention relates to methods and therapeutic combinations useful for improving clinical outcomes in diabetic patients having complications of diabetes such as diabetic nephropathy and/or metabolic syndrome.
[0004] Endothelins (ETs), particularly ET-1, are believed to play a role in
mediating the damaging effects of hyperglycemia in the kidney and elsewhere.
Expression of ET-1 in endothelial cells of the renal vasculature is upregulated by hyperglycemia; the potent profibrotic action of ET-1 thus generated in the kidney is believed to be involved in the morphologic changes seen in diabetic nephropathy. ET-1 acts via endothelin A (ETA) and endothelin B (ET.sub.B) receptors. Elevated plasma ET levels have been reported in patients with diabetes mellitus. See, for example, Takahashi et al. (1990) Diabetologia
33:306-310.
[0010] Avosentan, which may be classified as a selective ET.sub.A or dual
ET.sub.A/ET.sub.B receptor antagonist, has been reported to be in Phase III
clinical development for diabetic nephropathy. See Battistini et al. (2006)
Exp. Biol. Med. 231:653-695.
[0013] On the other hand, Shaw et al. (2006) Exp. Biol. Med.
231:1101-1105 reported that in a mouse model of non-obese type 1 diabetes, the
selective ET.sub.A receptor antagonist LU 208075 (ambrisentan) did not reduce the elevated plasma glucose levels seen in untreated animals.
[0035] The term "diabetic nephropathy" as used herein will be understood to include both incipient and overt stages of diabetic nephropathy, whether
diagnosed or not, but most typically as diagnosed by a clinician or physician.
The term "metabolic syndrome" as used herein refers to a complex of obesity,
hypertension, dyslipidemia and diabetes marked by a degree of insulin
resistance. The existence of metabolic syndrome as a true clinical syndrome is
not universally accepted; it will be understood that in the present context a
patient having metabolic syndrome is one exhibiting a complex of conditions as
itemized above, whether or not "metabolic syndrome" is formally diagnosed in
the patient.
[0051] Suitable selective ET.sub.A receptor antagonists can be identified by
one of ordinary skill from literature on such antagonists, based on the
disclosure herein, but a non-limiting list of such antagonists includes
ambrisentan, atrasentan, avosentan, BMS 193884, BQ-123, CI-1020, clazosentan, darusentan, edonentan, S-0139, SB-209670, sitaxsentan, TA-0201, tarasentan, TBC 3711, tezosentan, YM-598, ZD-1611 and ZD-4054, as well as salts, esters, prodrugs, metabolites, tautomers, racemates and enantiomers thereof.
Kopp teach: The role of Endothetin-l[ET-1] in the Pathogenesis of HIV-associated Nephropathy[HIVAN]" (see abstract provided by Applicant in IDS 4/24/12; as well as IDS statement below that copy provide is not legible; though the title in the IDS list sufficient to apply the reference relevant to the subject matter as presently claimed); as well as diagnose nephropathy (art-recognized that elevated ET-1 levels indicative of some type of nephropathy as presently claimed, based on teachings of Kopp).
Either Roden or Kopp (e.g. use of ET-1 antagonists such as ambrisentan for the nephropathy species HIVAN), teach and/or suggest to one of ordinary skill in the art at the time of the invention to treat other form and/or subspecies of nephropathy (e.g. FSGS or HIVAN), diagnose general nephropathy (by the steps claimed therein) in Roden, especially where Roden uses the same agent here (the known ET-1 antagonist ambrisentan); or Kopp teaching that HIVAN is ET-1 associated (and art-recognized if not in the abstract that a known ET-1 antagonist would be the 1st line treatment option); either alone and/or in view of the other; because the formerly claimed types of nephropathy (HIVAN)/renal disorder (FSGS) are both known to be negatively associated with the ET-1 pathway; where the ET-1 pathway is known to be treatable (to some degree) with ET-1 antagonists. Additionally to apply known steps to diagnose/monitor nephropathy in view of either/both alone or in view of the other. For at least the rational under KSR of (C) Use of known technique to improve similar devices (methods, or products) in the same way (here another form of nephropathy falling under the same ET-1 pathway and using the same ET-1 antagonists (e.g. ambrisentan)).
Equally, methods of monitoring the effectiveness of such treatment (standard practice) as in instant claims 38-46 even if not anticipated, would have been prima facie obvious based on the prior art combination against the backdrop of the state of the art and PHOSITA’s appreciation of following routine protocol thereto.
Applicant has added new claims 46 and 47 by amendment. New claim 46 is directed to treating any nephropathy with an ET-1 antagonist alone, which is rendered obvious under the same rationale already applied above. New claim 47 is merely drawn to routes of administration options already taught by the prior art of record applied (see passages above).
Based on the teachings of the reference(s), one of ordinary skill in this art at the time of the invention, would have had the rationale and reasonable expectation of success in arriving at the claimed invention, as a whole; which is deemed prima facie obvious.
Response to Amendments/Arguments
Applicant’s response (amendments and arguments) have been fully considered but are not yet found persuasive. Under the broadest reasonable interpretation of the claimed invention, The prior art combination is still deemed to teach and/or suggest treating nephropathies generally with ET-1 antagonists. Such would not preclude an ET-1 antagonist as being the sole active agent administered, under the rationale that the ET-1 antagonist was recognized as providing certain antagonistic benefits – including alone - for which nephropathies generally would benefit, as supported by the prior art of record and the state of the art on ET-1 and antagonist thereof (MPEP 2144.03, common knowledge). Notwithstanding that Rodin’s results pointed to an increase in ET-1, rather than a decrease, such was nevertheless recognized as an antagonist of ET-1 within the art, of which PHOSITA recognizes. The selection other ET-1 antagonist would have been merely a matter of selection from a finite number of options, and prima facie obvious therefrom – including alone, as a solo treatment. While applicant’s arguments have been fully considered they are not yet deemed persuasive based on the prior art combination teachings as a whole against the state of the art that ET-1 antagonists would have been expected to reduce ET-1 levels even if some results vary. Thus, the prima facie case of obviousness as such is maintained, absent further arguments, amendments, and/or evidence (test data, declaration).
Double Patenting – Maintained, No Arguments, Request for Abeyance
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 27-28, 31, 35-39, 42, and 46-47 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11,874,283 (IgA nephropathy); U.S. Patent No. 11,372,005 and 10,866,249 (both of varying scope to HIV-associated nephropathy (HIVAN); U.S. Patent No. 9,255,931 (focal segmental glomerulosclerosis (FSGS). Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed invention is drawn to treating any nephropathy – which includes any the species issued in the patents above - directly linked to increased levels of ET-1 compared to ET-1 levels in those without the nephropathy with the claimed ET-1 antagonists.
Claims 27-28, 31, 35-39, 42, and 46-47 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the copending application published as U.S. Patent Publication No. 20220260590 (glomerulonephritis), for which an obviousness double patenting rejection has been applied. Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed invention is drawn to treating any nephropathy – which includes the species glomerulonephritis of ‘590 - directly linked to increased levels of ET-1 compared to ET-1 levels in those without the nephropathy with the claimed ET-1 antagonists.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/MAURY A AUDET/Primary Examiner, Art Unit 1654
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