DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed on 8/12/25 has been entered; no amendments are indicated. Claims 119-146 are pending.
Election/Restrictions
Applicants’ election of Invention I, claims 119-131, in the reply filed on 8/12/25 is acknowledged. There is no indication of whether the election is with or without traverse, but because the response did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). Claims 132-146 (Invention II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elections of (1) ENPP1-Fc as the species of agent, and (2) saline as the species of carrier in the reply are also acknowledged. The elected species read on each claim in the elected invention.
Claims 119-131 are under consideration, as they read upon the elected species.
Specification
The disclosure is objected to because of the following informalities:
---The title of the invention is not descriptive, because (1) it is directed in part to compositions, but the claims are limited to methods, and (2) it is directed in part to any method for treating peripheral artery disease but the claims are limited to administration of an EPP1 or EPP3 agent. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Methods for Treating Peripheral Artery Disease with an ENNP1 or ENNP3 agent”.
Appropriate correction is required.
Claim Objections
Claims 119-131 are objected to because of the following informalities:
In claim 119, the term “ENNP” should be accompanied by the full terminology the first time it appears in a series of claims; e.g., “ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENNP1)”; see the specification at page 17.
In claim 127, line 3, “in mammal” should be “in a mammal”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Note on Prior Art Rejection(s)
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 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 119, 121-122, 125-128 and 130-131 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khan et al, WO 2019/067502 A1, published 4/4/2019 (cited on a 8/17/23 IDS). The earliest date to which the instant application claims priority is 5/7/20.
Independent claim 119 encompasses a method of treating a subject having peripheral artery disease (PAD) comprising administering to the subject an effective amount of an ENPP1 agent. Khan teaches “methods for treating a human patient having a cardiovascular disease” (CVD) comprising “administering to the patient one or more doses of a recombinant human soluble ectonucleotide pyrophosphatase phosphodiesterase (hsNPP1), active fragment or fusion protein thereof” (page 3, lines 8-11). NPP1 is another name for ENPP1, and therefore the protein administered by Khan is an ENPP1 agent. Khan further teaches that the exemplary CVDs to be treated include PAD (page 3, line 15). As such, the teachings of Khan anticipate claim 119.
Claim 121 encompasses a method of claim 119 wherein the ENPP1 agent is an ENPP1 polypeptide. The teachings of Khan that anticipate claim 119 are directed to administering soluble NPP1 (which is another name for ENPP1), an active fragment or a fusion protein thereof, each of which is polypeptide. As such, the teachings of Khan also anticipate claim 121.
Claim 122 encompasses a method of claim 119 wherein the subject does not have a deficiency of ENPP1. The subjects with CVD of Khan are not indicated to have a deficiency of ENPP1. As such, the teachings of Khan also anticipate claim 122.
Claim 125 encompasses a method of claim 121 wherein the ENPP1 polypeptide comprises an extracellular or catalytic domain of ENPP1. Khan further teaches that the soluble NPP1 of the invention has “a biologically active NPP1 domain” that is a “extracellular catalytic domain” (page 17, lines 13-15). As such, the teachings of Khan also anticipate claim 125.
Claim 126 encompasses a method of claim 121 wherein the ENPP1 polypeptide comprises amino acids 99-925 of SEQ ID NO: 1. Khan teaches a wild-type NPP1 protein having the amino acid sequence of SEQ ID NO: 1, which is identical to instant SEQ ID NO: 1. As such, the teachings of Khan also anticipate claim 126.
Claims 127, 128, 130 and 131 encompass a method of claim 121 wherein the ENPP1 polypeptide is fused to a heterologous protein that increases the circulating half-life of the ENPP1 in a mammal (claim 127) and further wherein the heterologous protein is an Fc region of an immunoglobulin IgG1 molecule (claim 128) that is carboxy terminal to the ENPP1 (claim 131). or wherein the ENPP1 agent is ENPP1-Fc. Khan further teaches the soluble NPP1 fused to the Fc region of an IgG1 molecule (page 17, lines 22-31), and further teaches that the preferred fusion proteins from “N-terminus to C-terminus” include “an NPP1 component, optionally a linker, an Fc region of an immunoglobulin” (page 24, lines 9-10). As such, the teachings of Khan also anticipate claims 127, 128, 130 and 131.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 120 is rejected under 35 U.S.C. 103(a) as being unpatentable over Khan et al, WO 2019/067502 A1, published 4/4/2019 (cited on a 8/17/23 IDS), as applied to claim 119 above, and further in view of Hardman et al, 2014. Semin Intervent Radiol. 31: 378-388.
Claim 120 encompasses a method of claim 119 wherein the subject has Stage III or Stage IV PAD.
The teachings of Khan that anticipate parent claim 119 are set forth above. While Khan teaches treatment of a subject having PAD, Khan does not further specify the stage of the PAD.
Hardman reviews “Classification Systems in Peripheral Artery Disease” (see title), teaching that the Fontaine system “grades the clinical presentation of patients to four stages”, based solely on symptoms, with Stage III having “[r]est pain, mostly in the feet” and Stage IV having “Necrosis and/or gangrene of the limb” (Table 1).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating a subject having PAD by administering an amount of an ENPP1 protein as taught by Khan and modify it to treat a subject having Stage III or IV PAD as taught by Hardman. Such a change represents taking a teaching directed to a genus (i.e., patients having PAD) and simply applying it to a subgenus that is well-recognized in the prior art and constitutes a large proportion of the patient population (i.e., patients having Stage III or IV PAD). The person of ordinary skill in the art would have had a reasonable expectation of success in treating PAD in such a subgenus because such merely represents treating the same disease in those subpopulations of the indicated disease having more severe symptoms. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 123 is rejected under 35 U.S.C. 103(a) as being unpatentable over Khan et al, WO 2019/067502 A1, published 4/4/2019 (cited on a 8/17/23 IDS), as applied to claim 119 above, and further in view of Slovut et al, 2012. Circulation. 126: 1127-1138.
Claim 123 encompasses a method of claim 119 wherein the subject having PAD has a condition that requires surgery on said peripheral artery (claim 123).
The teachings of Khan that anticipate parent claim 119 are set forth above. While Khan teaches treatment of a subject having PAD, Khan does not further teach that such a patient has a condition requiring surgery on said peripheral artery.
Slovut reviews “Surgical Technique and Peripheral Artery Disease” (Title), teaching that “Although the rate of bypass is decreasing, surgery remains an important component in the armamentarium for treating patients with advanced vascular disease. Surgical revascularization is indicated in patients with acceptable surgical risk who require a more durable repair, in those with lesions technically unsuitable for endovascular repair, and in patients who experienced failure of endovascular repair” (page 1127).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating a subject having PAD by administering an amount of an ENPP1 protein as taught by Khan and modify it to treat a subject having PAD and requiring surgery on a peripheral artery as taught by Slovut. Such a change represents taking a teaching directed to a genus (i.e., patients having PAD) and simply applying it to an art-recognized subgenus (i.e., patients having PAD and requiring surgery). The person of ordinary skill in the art would have had a reasonable expectation of success in treating PAD in such a subgenus because the necessity for surgery in such a patient does not obviate the need to treat the underlying condition, i.e., PAD. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 124 is rejected under 35 U.S.C. 103(a) as being unpatentable over Khan et al, WO 2019/067502 A1, published 4/4/2019 (cited on a 8/17/23 IDS), as applied to claim 119 above, and further in view of Olin et al, 2005, Vascular Medicine. 10: 241-246.
Claim 124 encompasses a method of claim 119 wherein the subject has hypertension.
The teachings of Khan that anticipate parent claim 119 are set forth above. Khan further teaches that the ENPP1 protein can be used for treatment of hypertension, e.g., at page 3, lines 21-25. While Khan teaches that the ENPP1 protein can be used for treatment of PAD or hypertension, Khan does not expressly teach treatment of subject having both PAD and hypertension.
Olin reviews the association between hypertension and PAD, teaching that “50-92% of patients with PAD have hypertension” (page 241).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating a subject having PAD by administering an amount of an ENPP1 protein as taught by Khan and modify it to treat a subject having both PAD and hypertension as taught by Olin. In view of the teachings of Olin, the person of ordinary skill in the art would have recognized that a majority of patients with PAD also have hypertension, and would have reasonably expected the therapy to also be beneficial in such patients in view of the teachings of Khan that the ENPP1 protein can be used for treatment of either condition. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 129 is rejected under 35 U.S.C. 103(a) as being unpatentable over Khan et al, WO 2019/067502 A1, published 4/4/2019 (cited on a 8/17/23 IDS), as applied to claim 119 above, and further in view of Slovut et al, 2012. Circulation. 126: 1127-1138, as applied to claim 123, and further in view of Thukkani et al, 2015. Circ Res. 116: 1599-1613.
Claim 129 encompasses a method of claim 123 wherein the subject having PAD and a condition that requires surgery on said peripheral artery, further requires the surgery due to a prior placement of a non-eluting stent in said artery, or a stent eluting a drug other than ENPP1 or ENNP3.
The method of parent claim 123 is obvious over the teachings of Khan in view of Slovut for the reasons set forth above. As described above, surgery is indicated for PAD patients “who experienced failure of endovascular repair”. Neither Khan nor Slovut further teach that such endovascular repair constitutes a prior placement of a stent.
Thukkani reviews “Endovascular Intervention for Peripheral Artery Disease”, teaching that stenting is a mainstay of endovascular therapy (see Abstract). Thukkani further teaches that “restenosis” remains one of the major limitations of stenting. Thukkani teaches that stents include bare-metal stents and drug-eluting stents (page 1603).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating a subject having PAD by administering an amount of an ENPP1 protein as taught by Khan and modify it to treat a subject having PAD and requiring surgery on a peripheral artery as taught by Slovut due to restenosis of a bare-metal (i.e., non-eluting) stent as taught by Thukkani. Such a change represents taking a teaching directed to a genus (i.e., patients having PAD) and simply applying it to an art-recognized subgenus (i.e., patients having PAD and requiring surgery due to restenosis of a bare-metal stent). The person of ordinary skill in the art would have had a reasonable expectation of success in treating PAD in such a subgenus because the necessity for surgery due to failure of a stent in such a patient does not obviate the need to treat the underlying condition, i.e., PAD. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Double Patenting
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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer (TD) 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 §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A TD must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains TD forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 (eTD) may be filled out completely online using web-screens. An eTD that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTDs, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 119, 121-123 and 125-131 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 166-179 of U.S. Application 18/058,712, filed 11/23/22, and claiming priority to 5/27/20, and which shares two applicants and three inventors with the instant application, and further in view of Slovut et al, 2012. Circulation. 126: 1127-1138 and Thukkani et al, 2015. Circ Res. 116: 1599-1613.
Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Instant independent claim 119 encompasses a method of reducing and/or preventing progression of vascular smooth muscle cell (VSMC) proliferation in a peripheral artery of a subject having peripheral artery disease (PAD) comprising administering to the subject an effective amount of an ENPP1 agent.
Independent claim 166 of ‘712 is directed to a method for reducing progression of VSMC in a subject having a tissue injury or a subject who has a condition requiring a surgery at a surgical site comprising administering an effective amount of an ENPP1 agent. Dependent claim 168 further limits the tissue injury to one that comprises “a prior stent placement in an artery”.
Slovut reviews “Surgical Technique and Peripheral Artery Disease” (Title), teaching that “Although the rate of bypass is decreasing, surgery remains an important component in the armamentarium for treating patients with advanced vascular disease. Surgical revascularization is indicated in patients with acceptable surgical risk who require a more durable repair, in those with lesions technically unsuitable for endovascular repair, and in patients who experienced failure of endovascular repair” (page 1127).
Thukkani reviews “Endovascular Intervention for Peripheral Artery Disease”, teaching that stenting is a mainstay of endovascular therapy (see Abstract). Thukkani further teaches that “restenosis” remains one of the major limitations of stenting. Thukkani teaches that stents include bare-metal stents and drug-eluting stents (page 1603).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of reducing progression of VSMC in a subject having a tissue injury comprising administering an effective amount of an ENPP1 agent of claim 166 of ‘712 and modify it to apply the method to a patient with PAD requiring surgery on a peripheral artery as taught by Slovut due to restenosis of a bare-metal (i.e., non-eluting) stent as taught by Thukkani. Such a change represents taking a teaching directed to a genus (i.e., patients having a tissue injury due to a prior placement of a stent in an artery) and simply applying it to an art-recognized subgenus (i.e., patients having PAD and having a tissue injury due to a prior placement of a stent in an artery). The person of ordinary skill in the art would have had a reasonable expectation of success in reducing the progression of VSMC in such a subgenus because the patient meets the criteria established by the claims of ‘712 (tissue injury due to a prior placement of a stent in an artery), and there is no suggestion that such a treatment would not be applicable to such patients. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Instant claims 121 depend from claim 119 and each further limit the method to embodiments that correspond to the further limitations of the method of the dependent claims of ‘712 in the following manner.
Instant Claim
Claim of ‘712
121
173
122
167
123
119
125
174
126
175
127
177
128
178
129
169
130
176
131
179
Claim 120 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 166-179 of U.S. Application 18/058,712, filed 11/23/22, and claiming priority to 5/27/20, and which shares two applicants and three inventors with the instant application, and further in view of Slovut et al, 2012. Circulation. 126: 1127-1138, and Thukkani et al, 2015. Circ Res. 116: 1599-1613, as applied to claim 119, and further in view of Hardman et al, 2014. Semin Intervent Radiol. 31: 378-388.
Claim 120 encompasses a method of claim 119 wherein the subject has Stage III or Stage IV PAD.
Hardman reviews “Classification Systems in Peripheral Artery Disease” (see title), teaching that the Fontaine system “grades the clinical presentation of patients to four stages”, based solely on symptoms, with Stage III having “[r]est pain, mostly in the feet” and Stage IV having “Necrosis and/or gangrene of the limb” (Table 1).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method obvious over claim 119 of ‘712 in view of the teachings of Slovut and Thukkani and modify it to apply it to a PAD patient having Stage III or IV PAD. Such a change represents taking a teaching directed to a genus (i.e., patients having PAD) and simply applying it to an art-recognized subgenus (i.e., patients having Stage III or IV PAD). The person of ordinary skill in the art would have had a reasonable expectation of success in treating PAD in such a subgenus because such merely represents treating the same disease in those subpopulations having more severe symptoms. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 124 is rejected under 35 U.S.C. 103(a) as being unpatentable over is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 166-179 of U.S. Application 18/058,712, filed 11/23/22, and claiming priority to 5/27/20, and which shares two applicants and three inventors with the instant application, and further in view of Slovut et al, 2012. Circulation. 126: 1127-1138, and Thukkani et al, 2015. Circ Res. 116: 1599-1613, as applied to claim 119, and further in view of Olin et al, 2005, Vascular Medicine. 10: 241-246.
Claim 124 encompasses a method of claim 119 wherein the subject has hypertension.
Olin reviews the association between hypertension and PAD, teaching that “50-92% of patients with PAD have hypertension” (page 241).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method obvious over claim 119 of ‘712 in view of the teachings of Slovut and Thukkani and modify it to treat a subject having both PAD and hypertension as taught by Olin. In view of the teachings of Olin, the person of ordinary skill in the art would have recognized that a majority of patients with PAD also have hypertension, and would have reasonably expected the therapy to also be beneficial in such patients in the absence of any evidence contraindicating replacement of stents in patients having co-morbid PAD and hypertension. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
The above rejections over the claims of ‘712 are provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
It is noted that while the above double patenting rejections are provisional, the instant application claims priority to the same “patent term filing date” (5/27/21) as the '712 application, taking into account any benefit under 35 U.S.C. 120, 121, 365(c), or 386(c)). Per MPEP 804.I.B.1.(b).(ii):
“If both the application under examination and the reference application have the same patent term filing date, the provisional nonstatutory double patenting rejection made in each application should be maintained until it is overcome. Provisional nonstatutory double patenting rejections are subject to the requirements of 37 CFR 1.111(b). Thus, applicant can overcome a provisional nonstatutory double patenting rejection by filing a reply that either shows that the claims subject to the rejection are patentably distinct from the claims of the reference application, or includes a compliant terminal disclaimer under 37 CFR 1.321 that obviates the rejection. If the reply is sufficient, the examiner will withdraw the nonstatutory double patenting rejection in the application in which it was submitted."
Thus, per MPEP 804, the provisional double patenting rejections set forth above should be maintained in the instant application unless overcome as indicated therein.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674