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 .
Applicant’s response (amendment, arguments) filed with the RCE is acknowledged. Based on the arguments and amendments, an updated search was carried out which yielded a new reference Wolf (1998), applied below in the rejection(s) of record.
Claims 38-40, 43-52 and 54-63 (58-63 new), after the amendment, are the claims now pending and examined on the merits.
Claim Scope Interpretation: An ET-1 level of "about" 4 pg/ml as to the threshold level triggering administration - and deemed definite as defined by a standard of +/- 10% in para 19 - has been expressly amended into the base claims 38, 44, 49 (the three (3) methods claimed directed to treating, monitoring, and diagnostic):
[0019] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about”. Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently disclosed subject matter. As used herein, the term “about,” when referring to a value or to an amount of mass, weight, time, volume, concentration or percentage is meant to encompass variations of in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1% from the specified amount, as such variations are appropriate to perform the disclosed method.
Election/Restrictions – Withdrawn
Applicant’s arguments are deemed persuasive and the claims are examined on the merits as drawn to the genus of treating any glomerulitis condition, including the elected membranoproliferative glomerulonephritis with any of the ET-1 antagonists.
Claim Rejections - 35 USC § 103 – Obviousness – Maintained, Modified
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 though 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 38-40, 43-52 and 54-63 remain/are rejected under 35 U.S.C. 102(b) as anticipated by or, in the alternative, under 35 U.S.C. 103(a) as obvious over either
Claim Scope/Interpretation (Previously Noted): An ET-1 level of "about" 4 pg/ml as to the threshold level triggering administration (defined in para 19 as +/-10%) had been expressly amended into the base claims 38, 44, 49 (the three (3) methods claimed directed to treating, monitoring, and diagnostic). This did not alter the previous disposition, absent further evidence to the contrary, as the prior art combination already teach weighing ET-1 levels as an indicator of disease and naturally therewith weighing baseline levels for which “about 4 pg/ml” is deemed such and any level about or below a triggering event for determining next steps. Applicant has provided no evidence or arguments that the about 4 pg/ml was either not known as the baseline or some new critical/essential triggering point relevant to treatment, monitoring, and/or diagnosis. Thus, without more, such is deemed a known parameter that PHOSITA was aware of relevant to ET-1 levels as parameters routinely weighed relevant to treatment, monitoring, and diagnosis tied to glomerulonephritis generally.
Here, on the evidentiary side, Wolf (1998) is applied as finding that glomerunephritis plasma ET-1 levels were not found to be indicative of disease v. non-disease (e.g. v. controls) relevant to the glomerulonephritis subspecies tested. Thus, absent evidence that one more or more subspecies of glomerulonephritis are shown indicative of disease based on plasma ET-1 levels – which the present specification is found to provide no evidence/test data for any (see response to arguments below) – it would appear that the prior art was aware that ET-1 ‘may’ have a role in glomerulonephritis and therefore be open to ET-1 plasma level testing and treatment with an ET-1 antagonist (per the state of the art also discussed in Wolf (1998)). (But see Wolf (1998) also applied in the new 35 USC 112(a) written description rejection below).
Roden et al. (US20090054473) in view of KOPP 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-P9O2496 (2008). (abstract only (illegible copy cited in the IDS of 4/24/12; see IDS note, bottom)); or vice-versa; and further in view of Wolf et al. ((1998) Endothelin-1 and Endothelin-3 Levels in Different Types of Glomerulonephritis. Journal of Cardiovascular Pharmacology 31: p S482-S485. https://journals.lww.com/cardiovascularpharm/fulltext/1998/00001/Endothelin_1_and_Endothelin_3_Levels_in_Different.138.aspx); and in line with MPEP 2144.03 (common knowledge) 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 conditi3ons they could treat (such as ambrisentan; nephropathies such as HIVAN or FSGS).
Roden teach the use of elected species ambrisentan (product/composition/kit) to treat and/or 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 (ET.sub.A) 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 in claim 9, based on teachings of Roden in view of Kopp).
[HIVAN is a known type of glomerulonephritis.]
Wolf teach that glomerulapthies such as various types (species) of glomerulonephritis were taught in the state of the art for being treated with ET antagonists, of which ET-1 is discussed therein (see abstract; cited references thereto):
“There is evidence that an activated renal endothelin (ET) system is involved in development of glomerulosclerosis. However it is still unknown if different ETs are involved in the pathogenesis of various types of glomerulonephritis (GN). This study characterized ET-1 [ ] levels in patients suffering from chronic GN. [ ] These data indicate an important role for the ET-1 [ ] systems in the pathophysiology of different forms of GN. This is significant with regard to an early preservation of renal function at the onset of GN by the use of selective ET antagonists”.
Based on Roden in view of Kopp, or vice versa, and further in view of Wolf, it would have been obvious to one of ordinary skill in the art at the time of the invention to treat other form and/or subspecies of nephropathy, including glomerulonephritis, diagnose general nephropathy in Roden, especially where Roden uses the same agent elected here (the known ET-1 antagonist ambrisentan); or Kopp teaching that HIVAN (a type of glomerulonephritis) 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 presently 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 nephropathy (present claim 9) 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/glomerulonephritis falling under the same ET-1 pathway and using the same ET-1 antagonists (e.g. elected ambrisentan)).
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 – treating any glomerulonephritis (including membranoproliferative glomerulonephritis, FSGS, HIVAN, etc.) with any ET-1 antagonist (including elected ambrisentan) and methods of diagnosis employing the same - as a whole; which is deemed prima facie obvious.
Response to Amendments and Arguments
Applicant’s amendments and arguments have been fully considered but not yet found persuasive. The amendments are simply to further new dependent claims in line with those already present in the independent and/or dependent claims. The arguments in summary attempt to traverse the prior art combination rejection of record asserting that Roden and Kopp are not directed to glomerulonephritis per se; however, even if true, the newly applied reference to Wolf (1998) fills this gap by teaching glomerulonephritis and treatment with ET antagonists generally, while also discussing ET-1 specifically therein. Applicant secondarily argues that the presnt specification teaches test data on HIVAN and FSGS support the instantly claimed use in glomerulonephritis (see response page 9) – yet without any test data on the later as filed. This argument is also not persuasive as applicant cannot make the argument that Roden and Kopp provide insufficient nexus to render obvious the instantly claimed invention (now supplemented with Wolf (1998); and then turn right around and assert the same lack of direct evidence on glomerulonephritis in applicant’s own specification is nevertheless fully supportive of that instantly claimed. Applicant provides no evidence of their own showing the instant claim scope was achieved for treating one or more types of glomerulonephritis based on about 4 pg/ml as the dividing line for treatment v. no treatment (see also 35 USC 112(a) written description rejection applied employing other teachings of Wolf (1998)). The choice of administering above or below or about 4 pg/ml would have merely been a matter of selection absent evidence of criticality based on actual test data for which no evidence thereof has been uncovered and/or argued nor provided via post-filing evidence by declaration.
Thus, neither the amendments and/or arguments nor the evidence of record are found persuasive to overcome the obviousness rejection. The rejection is maintained (modified) for the reasons of record, further supported by Wolf (1998) as evidencing that the state of the art was administering ET antagonists in the treatment of glomeropathies (the genus of which includes the instantly claimed glomerulonephritis), with discussion therein of ET-1 equally.
As previously set forth and still relevant to the newest arguments by applicant:
As evidence of this, primary reference Roden teach the following as to the relevance of ET-1 levels of which para 15 in particular evidence the monitoring of ET-1 levels – which equates to baseline ET-1 levels (e.g. about 4 pg/ml being known by PHOSITA based on Roden alone, as the instantly claimed glomerulonephritis being a known type of nephropathy/kidney disease discussed in Roden) as indicative of treatment impacts and a parameter allowing monitoring of kidney/glomelular function below:
[0009] Sorokin & Kohan (2003) Am. J. Physiol. Renal Physiol. 285:F579-F589 remarked that the stage was set for clinical trials of ET inhibitors in patients with glomerular disease characterized by increased ET-1 production and actions.
[0014] [ ] It was further reported that ET.sub.A receptor blockade by atrasentan led to an increase rather than a decrease in plasma ET-1 levels.
[0015] Shaw & Boden (2005) Current Vascular Pharmacology 3:359-363 reviewed evidence on effects of ET-1 and proposed that chronically elevated ET-1 levels may be a cause of insulin resistance and impaired glucose tolerance in early stages of type 2 diabetes, obesity and metabolic syndrome. [ ]
Description
[0675] Several of the comorbidities mentioned above as occurring in elderly diabetic patients have been individually reported in the literature (including literature cited herein) to be mediated by ET-1 and/or to be treatable with a selective ET.sub.A receptor antagonist. [ ] However, even without such contribution by the selective ET.sub.A receptor antagonist to more than one comorbidity, the adjunctive or combination therapy of the present embodiment brings great benefit . . .by enabling a complex of comorbidities, as seen for example in diabetic nephropathy or metabolic syndrome, to be simultaneously addressed.
TABLE-US-00003 LIST OF ABBREVIATIONS [ ] Estimated glomerular filtration rate ET-1 Endothelin-1 ET.sub.A [ ]
Notwithstanding the above, the following evidentiary reference is cited to Chacko (U.S. Patent Publication No. 20120177665, priority date 9/29/090) - directed to using the 4 pg/ml parameter as about a maximum threshold determinant for diagnosis, monitoring, and treatment (title, abstract) of other related disorders (namely from the kidneys into the bladder relevant to cystitis) – is cited merely to set forth the about 4 pg/ml was art-recognized at the time of filing as the accepted upper limit as to ET-1 levels by PHOSITA:
METHOD OF DIAGNOSING AND TREATING INTERSTITIAL CYSTITIS
DOCUMENT ID
US 20120177665 A1
DATE PUBLISHED
2012-07-12
Description
[0017] FIG. 1 is a bar graph showing the results of an ELISA assay for ET-1 in human urine. The concentration of ET-1 in the urine of female patients with IC (n=5; dark bar) is contrasted with that of normal healthy women (n=4; light bar). The results show that the average ET-1 level is 2.9.+-.1.9 pg/ml in urine from the normal control group. The average ET-1 level increases to 10.7.+-.2.3 pg/ml in urine from IC patients. These data from five women with IC compared with that from four normal women, indicates that there is an increased amount of Endothelin in the urine of patients with IC.
[0036] As described above, "normal" levels of ET-1 in a population can vary based upon any variables in an individual assay used for measurement and the standardization of regents employed in such assay. Therefore, in one embodiment of this invention, i.e., that based upon the assay and antibody employed in the examples below, the "normal" level of urinary ET-1 ranges between and including the concentrations 1.0 and 4.0 pg/ml. For example, according to the ELISA assay employed in the examples below, average levels of urinary ET-1 were 2.9.+-.1.9 pg/ml in urine from the normal control group. However, in another assay, the "normal" value may skew somewhat from the minimum average of 1.0 pg/ml or maximum average of 4.0 pg/ml. Increasingly sensitive assays may further affect the "normal" range of ET-1 in the biological samples of a population. However, other averages within the ranges may be obtained for larger populations or populations of patients differing in other physiological characteristics, e.g., gender, weight, physical condition, etc. or for other types of biological samples.
[0037] Thus, for purposes of this invention when using an ELISA, particularly the ELISA and reagents of the examples below, a diagnosis of IC may be obtained when a subject's urinary ET-1 is significantly elevated above 4.0 pg/ml. For example, the results of Example 3 demonstrate that the average urinary ET-1 concentration in IC patients was 10.7.+-.2.3 pg/ml. Thus, in one embodiment of the diagnostic method of this invention a diagnosis of IC may be made when a subject's urinary ET-1 level is greater than 4 pg/mI. In another embodiment of the diagnostic method of this invention a diagnosis of IC may be made when a subject's urinary ET-1 level is greater than 5 pg/ml. In yet another embodiment of the diagnostic method of this invention a diagnosis of IC may be made when a subject's urinary ET-1 level is or greater than 6 pg/ml. In yet another embodiment of the diagnostic method of this invention a diagnosis of IC may be made when a subject's urinary ET-1 level is or greater than 7 or 8 pg/ml. In yet another embodiment of the diagnostic method of this invention a diagnosis of IC may be made when a subject's urinary ET-1 level is or greater than 9 or 10 pg/ml, and so on.
[0097] Endothelin expression is quantitated at the protein level by enzyme linked immunosorbent assay (ELISA). ELISA is performed using the human big Endothelin-1 (ET-1) Enzyme Immunometric Assay kit (Assay Designs, Inc., Ann Arbor, Mich.) to determine human big ET-1 peptide levels in urine samples from five female IC patients. [ ]
[0099] The level of ET-1 in normal human urine is estimated to be in the range of 1.0 to 4.0 pg/ml, which falls easily in the linear range of this assay. The data from this analysis shows that urine of patients with IC demonstrates an elevation of ET-1 (FIG. 1). The average ET-1 level is 2.9.+-.1.9 pg/ml in urine from the normal control group, while the average ET-1 level increased to 10.7.+-.2.3 pg/ml in urine from the five IC patients. These data indicate that there is a greater than three-fold increase of Endothelin-1 in the urine of patients with IC than in the urine of healthy women. These data demonstrate a correlation between elevations of urinary ET-1 and IC that has not been shown before; thus a determination of urinary ET-1 serves as a biomarker for the diagnosis of IC.
Claims
4. The method according to claim 2, wherein the biological sample is urine and the level of expression of ET-1 is increased above 4 pg/ml.
The prima facie case of obviousness is maintained for the reasons of record, that it would have been obvious based on primary reference Roden to administer an ET-1 antagonist such as ambrisentan to a patient in need thereof having a nephropathy/kidney disease such a subclass thereunder of glomerulonephritis as claimed here, and using the now base claimed ET-1 level above about 4 pg/ml as a threshold for determining time for treatment, monitoring, and even diagnosing based on Roden alone or in view of Kopp (teaching the relevance of ET-1 to HIVAN - a known type of glomerulonephritis. Both Roden and Kopp teach the relevance of ET-1 levels in kidney disease which PHOSITA was aware in other kidney disorders (see also evidentiary reference to Chacko that about 4 pg/ml is the normal upper limit accepted by PHOSITA, above).
Double Patenting – Maintained,
No Response, Request for Abeyance Pending Allowable Subject Matter
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 38-40, 43-52 and 54-63 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Nos. 9255931 (FSGS), 10866249 (HIVAN), 11372005 (HIVAN), and 11877283 (IgA Nephropathy) – all species of the glomerulonephritis genus and all using the same ET-1 antagonists. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant invention is to the genus employing the same agents for treatment as the species in each of the earlier parents.
Claim Rejections - 35 USC § 112(a)(i)/(pre-AIA ) – Written Description – New,
Necessitated by Updated Search New Reference Uncovered (Wolf (1998)
The following is a quotation 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.
Claims 38-40, 43-52, and 54-63 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing/identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, applicant has claimed that any or all glomerulonephritis types/species are treatable with the claimed ET-1 antagonists in a subject in need thereof having a plasma ET-1 level of about 4 pg/ml.
The instant specification provides no test data for any type/species of glomerulonephritis as being treatable based on the claim scope above, thus lacking possession at the time of invention as to which type/species of glomerulonephritis may be treatable based on the instant claim scope.
Wolf et al. ((1998) Endothelin-1 and Endothelin-3 Levels in Different Types of Glomerulonephritis. Journal of Cardiovascular Pharmacology 31: p S482-S485. https://journals.lww.com/cardiovascularpharm/fulltext/1998/00001/Endothelin_1_and_Endothelin_3_Levels_in_Different.138.aspx) teach that for at least two (2) types/species of glomerulonephritis, plasma ET-1 levels were no different than controls – those without said type/species of glomerulonephritis (see test data results and discussion sections below):
“The plasma ET-1 levels in patients with MCN did not differ from those of controls(Fig. 1).”
Thus, based on Wolf (1998) plasma ET-1 levels would not guide PHOSITA as to diagnosing or when treatment should start of stop:
RESULTS
Endothelin-1
ET-1 levels in patients suffering from minimal change nephropathy (MCN) were enhanced in the spontaneous urine and in the 24-h urine compared to controls (all data are expressed as controls vs. GN): sp. urine, 157.2 ± 27 vs. 304 ± 70 pg/ml, p = 0.03; 24-h urine, 123 ± 12 vs. 224 ± 34 pg/ml, p = 0.01). The plasma ET-1 levels in patients with MCN did not differ from those of controls(Fig. 1).
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In the absence of sufficient recitation of distinguishing identifying characteristics between one type/species of glomerulonephritis and another, the specification does not provide adequate written description of the claimed genus for treating any glomerulonephritis based on the instant claim scope and a lack of test data thereof as originally filed to provide sufficient support/guidance and possession thereof.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111; clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry,whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Therefore, the full breadth of the claims are not presently deemed to have been in Applicant’s ‘possession’ and found to meet the written description provision of 35 U.S.C. §112.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAURY A AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on Monday-Thursday 8-630PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-272-0562. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAURY A AUDET/Primary Examiner, Art Unit 1654
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