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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/15/25 has been entered.
Claims Status
Claims 1,2,4,6,9,16-19,21,22,28 and 32-37 are pending in the application. Claims 21,22,28 and 32-36 are withdrawn from further consideration. Claims 11,14 and 20 are cancelled in the amendment filed 10/15/25.
Declaration/Affidavit
The declaration under 37 CFR 1.132 filed 10/15/25 is insufficient to overcome the rejection of claim 1,2,4,6,9,16-19 and 37 based upon 35 U.S.C. 103 as set forth in the last Office action because: the declaration describes the stent comprising CoCr oxide material that leads to P-O-Cr bonds The instant claim 6 is drawn to titanium oxide and/or nickel titanium oxide material. Therefore, the instant claim 6 is not commensurate in scope.
The declaration states that the coated stents showed remarkable stability even after 60 days,
marked reduction in platelet activation in comparison to control (bare metal) stents and complete patency without any systemic anti-platelet therapy for 90 days. Therefore, the coated stents of the disclosure perform significantly better than uncoated, bare metal stents. When compared to drug-eluting stents, the coated stents performed at least as well without systemic dual antiplatelet therapy, indicating non-inferiority and eliminating the bleeding risk associated systemic antiplatelet administration.
These statements are subjective and do not provide quantitative data.
Claim Rejections - 35 USC § 103
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 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1,2,4,6,9,16-19 and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 2006/0194008A1) in view of Agrawal et al. (US 2009/0123516A1) and in further view of Han et al. (US 2017/0087280A1).
Schwartz et al. (US 2006/0194008A1) discloses implantable substrates/devices comprising a native oxide, such as titanium metal, cobalt-chromium, stainless steel, etc. (p4, [0044]; p24, [0175]; p25,
[0186]) wherein the native metal oxide encompasses the metal oxide of the instant claims 1 and 37.
The titanium oxide encompasses the titanium oxide of the instant claim 6.
The implantable substrate comprises a phosphonate coating, such as organic phosphonic acids (p4, [0047]) comprising an alkylene between about 2 and about 40 carbon atoms (p4, [0048]; p11, [0101]).
The phosphorus-based coating forms self-assembled monolayers (FIG. 5; p1, [0005]; p33, [0231]) that encompass the phosphonic acid self-assembled monolayers of the instant claims 1 and 37.
The phosphorus-based coating has a first, inner surface and a second, outer surface. The first,
inner surface comprises organophosphate moieties bonded to the oxide surface of the implantable substrate p3, [0027]; p4, [0051]; p6, [0060]). The IR spectra demonstrated ordered phosphonate films in which substantially all the phosphonates were covalently bound by at least on one oxygen to the oxide surface (p37, [0263]).
The first inner surface encompasses the phosphonic head portion bonded to at least one oxygen on the surface of the metal oxide of the instant claims 1 and 37.
The second, outer surface exhibits functional groups at a position remote to or omega to the organophosphate moieties. The functional groups comprise amino groups for further chemical modification (p3, [0027]; p4, [0051]; p6, [0060]).
The amino outer surface functional group of the organophosphate encompasses the amine group opposite the head portion and spaced from the surface of the body of the instant claims 1 and 37.
The self-assembled monolayers may be derivatized with active agents, such as sirolimus, tacrolimus, fondaparinux, heparin, etc. or combinations thereof (p13, [0120]; p16, [0132]; p20, [0146-0147]) that encompass the sirolimus, tacrolimus and fondaparinux of the instant claim 1.
The organophosphate moieties of the self-assembled monolayers may also be unfunctionalized where the portion of the molecules remote to the end covalently bonded to the oxide surface has a
terminal group that contains a usually-non-reactive moiety (p23, [0166]).
The unfunctionalized end of the self-assembled monolayers encompasses the tail portion that are non-reactive with a therapeutic agent of the instant claim 17.
The implantable devices comprise vascular grafts, stents, valves, etc. (p25, [0186]; claim 25) that encompass the blood contacting device of the instant claim 2 and stent of the instant claim 4.
With regards to the instant claim 4, Schwartz et al. does not explicitly disclose that the stent comprises a plurality of interconnected elongated members that are optionally one or more of closed or open cells, helical coils, or radially expandable rings.
Agrawal et al. (US 2009/0123516A1) discloses a medical device comprising one or more self-
assembled monolayer (SAM) molecules attached to the surface of the medical device (abstract; p2, [0021]).
The medical device comprises an implant made of titanium, stainless steel (316L), cobalt, chromium, etc. (p2, [0023]; p3, [0026-0027]; p33-34, [0178]). The titanium comprises titanium oxide (p28, [0109]).
The SAM includes three parts- a middle portion and two end portions (covalently attached to each end of the middle portion) (p7, [0096]) wherein the two end portions comprise a first functional group and a second functional group (abstract; p3, [0024]). The SAM molecules can be attached to the surface of the device via a phosphonic acid, etc. (p3, [[0032]; p6, [0091-0092]; p7, [0103]).
One or more therapeutic agents, such as everolimus, tacrolimus, etc. are attached to the one or more SAMs (p2, [0023], p4, [0036],[0041]; p37, [0226])
The medical devices include a stent, etc. (p4, [0037]) that are small, expandable device inserted into a narrowed artery that are classified based on their pattern of metal construction (slotted tube, coil, or mesh) (p33, [0170]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention that the vascular stents of Schwartz et al. are expandable devices that may be formed of coils, etc. as Agrawal et al. teaches that vascular stents comprising analogous drug-containing phosphonate SAMs comprise small coils that are expandable in a narrowed artery.
With regards to the instant claims 9 and 37, Schwartz et al. does not explicitly disclose the SAM molecule comprises 12-aminododecylphosphonic acid.
Agrawal et al. discloses that the SAM molecules comprise an opposite end portion group, such as amine, etc. (p7, [0103]) including (12-aminododecyl)phosphonic acid (p10, right column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize 12-aminododecylphosphonic acid comprising a 12 carbon atom chain for the SAMs as Schwartz et al. teaches that the organic phosphonic acids have an alkylene between about 2 and about 40 carbon atoms and comprise an amino outer surface functional group for derivatization with a therapeutic agent.
With regards to the instant claim 19, Schwartz et al. does not explicitly disclose at least two different therapeutic molecules covalently bonded to the tail portion of each of the plurality of molecules of the self-assembled monolayer.
Schwartz et al. discloses that the self-assembled monolayers may be derivatized with active agents, such as sirolimus, tacrolimus, fondaparinux, etc. or combinations thereof (p13, [0120]; p16, [0132]; p20, [0146-0147]).
Agrawal et al. discloses that one or more therapeutic agents is attached to the one or more self-assembled monolayer molecules (p2, [0023], p4, [0041]; p37, [0226]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to bind one or more therapeutic agents to the SAMs of Schwartz et al. as Schwartz et al. teaches of the combination of drugs bound to the SAMs and as Agrawal et al. teaches one or more therapeutic agents attached the SAMs so that the drugs present at the implant interface provides a level of precision for highly consistent dose delivery of drugs.
With regards to the instant claim 18, Schwartz et al. does not explicitly disclose the ratio of molecules which are reactive with the therapeutic agent and the spacer molecules, which are non-reactive with the therapeutic agent is about 9:1.
Schwartz et al. further discloses that the functionalized self-assembled monolayers and the
unfunctionalized self-assembled monolayers may each comprise a surface functional group density of at least about 5 times, about 10 times, about 25 times, etc. (p23-24, [0168-0170]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to vary the ratio of functionalized self-assembled monolayers reactive with a therapeutic agent and the unfunctionalized self-assembled monolayers that are nonreactive with the therapeutic agent provided in the composition, according to the guidance provided by Schwartz et al., to provide a composition having the desired ratios and concentrations of therapeutic agents attached to the stents for the effective treatment of various conditions. It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regards to the instant claims 16 and 37, Schwartz et al. does not explicitly disclose that one of the two different therapeutic molecules is ticagrelor.
Han et al. (US 2017/0087280A1) discloses drug eluting stents made of titanium, stainless steel, cobalt-chromium, etc. (p2, [0017]; p3, [0041]) comprising multiple drugs, such as the antithrombotic agent ticagrelor, heparin, etc.(p2, [0025]; p3, [0037]) for preventing thrombosis and inhibit inflammation (p4, [0054]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the antithrombotic/anti-platelet agents fondaparinux or heparin of
Schwartz et al. for the antithrombotic agent ticagrelor of Han et al. as heparin and ticagrelor are used analogously as antithrombotic agents for the advantage of preventing thrombosis during implantation of the stent for the treatment of cardiovascular disease.
Response to Arguments
Applicant's arguments filed 10/15/25 have been fully considered but they are not persuasive.
Applicant asserts that the claimed device provides unexpected results: the coated stents showed remarkable stability even after 60 days, marked reduction in platelet activation in comparison to control (bare metal) stents and complete patency without any systemic anti-platelet therapy for 90 days. Therefore, the coated stents of the disclosure perform significantly better than uncoated, bare metal stents. When compared to drug-eluting stents, the coated stents performed at least as well without systemic dual antiplatelet therapy, indicating non-inferiority and eliminating the bleeding risk associated systemic antiplatelet administration.
These statements are subjective and do not provide quantitative data.
Applicant asserts that the effects are not reasonably predictable based on the disclosure of Agrawal, which discloses hundreds of potential SAM molecules without any particular guidance to select a SAM molecule
The reference of Schwartz specifically discloses organophosphonic acid SAM moieties comprising an alkylene chain of 4 to 20 atoms carbon which is a finite number of carbon atoms. The dodecylphosphonate is an exemplified carbon chain length, for example 12-phosphonododecylphosphonate.
The reference of Schwartz specifically discloses organophosphonic acid SAM moieties
comprising functional groups, such as hydroxyl, phosphonate, phosphate, amino and thiol groups from a finite list of functional groups.
The reference of Agrawal was used to teach of the 12-aminododecylphosphonate SAM derivative.
Applicant asserts that Agrawal discloses hundreds of potential therapeutic agents, ranging from anti-cancer agents, hormones, anesthetics, vasodilators, anti-coagulants, anti-inflammatories, anti-coagulants/anti-platelets, antibiotics, antifungals, analgesics, and opiates.
The references of Agrawal was not explicitly used to teach of the therapeutic agents but it would have been predictable to one of ordinary skill in the art to substitute one known therapeutic agent for another known therapeutic agent as long as it contains a reactive moiety capable of binding to the amino functional groups of the SAMs.
The reference of Schwartz was used to teach that self-assembled monolayers may be derivatized with active agents, such as sirolimus, tacrolimus, fondaparinux, heparin, etc. or combinations thereof. Also, it would have been predictable to one of ordinary skill in the art to substitute one known therapeutic agent for another known therapeutic agent as long as it contains a reactive moiety capable of binding to the amino functional groups of the SAMs.
Applicant asserts that in the cited references the combination of SAM and therapeutic agents can provide an organized tightly packed coating.
The reference of Schwartz teaches that the stability of the SAMs is due to the highly ordered packing of the alkyl chains in the monolayer (p40, [0284]).
The IR spectra demonstrated ordered phosphonate films in which substantially all the phosphonates were covalently bound by at least on one oxygen to the oxide surface (p37, [0263]).
The greater van der Waals interactions between longer chains may help facilitate ordered SAM
formation which may lead to greater surface densities for dodecane chain than for its C-4 analog (p38,
[0269]).
Therefore, the longer chain length SAMs of Schwartz are ordered and tightly packed.
Conclusion
No claims are allowed at this time.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618