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 .
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-6, 8-10, 12-14, 16—17, 20, and 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schedler et al. (WO 2018/210989) in view of Dickerson (US 5677276).
As to claim 1, Schedler et al. discloses a medical device comprising a substate and at least one functional layer that has biomimetic and/or bio-repulsive properties (see 0008 of the translation). The functional layer comprises sugar alcohols (saccharide) (see 0026 of the translation). Schedler further teaches the use of its coating on medical devices for endovascular, neurovascular or cardiovascular applications (see 0060). The device can be a permanent implant (see 0002).
Schedler et al. further teaches that its biomimetic and/or biorepulsive functional layer reduces thrombocyte recognition of the medical-device surface and thereby reduces platelet adhesion and aggregation. Schedler et al. attributes, at least a part, of the biorepulsive effect to steric repulsion and protein-repelling effects at the coated surface. (see 0055-56 of the translation).
Schedler et al. fails to teach the functional layer contains peptide sequences with integrin-binding motifs as required by claim 1.
Dickerson discloses conjugating saccharide polymers with peptides containing the integrin-binding motif Arg-Gly-Asp (RGD) for use as a coating a medical product to promote cell adhesion to biomaterial matrices (see abstract, col. 3, lines 50-55, and col. 6, lines 3-10). Dickerson teaches coating a prosthetic device with RGD-containing peptides promotes attachment of cells to the device.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to incorporate the integrin-binding peptides such as RGD of Dickerson into the functional coating of Schedler et al to provide the medical device surface with known integrin mediated cell interaction functionality taught by Dickerson. Dickerson further teaches association of the RGD peptides with saccharide polymers, thereby providing a known means of incorporating the peptide functionality into a saccharide-based biomaterial.
One would have been motivated to do so since both are directed to coating medical devices with saccharide based functional coatings and Dickerson further teaches that RGD peptides promote integrin-mediated cell attachment which would improve biological interaction of implant surfaces and conjugating such materials with saccharides. One of ordinary skill in the art would have had a reasonable expectation that the known RGD functionality would provide integrin-mediated cellular interaction when presented at the modified medical device surface because Dickerson teaches that peptides on the surface promotes cellular attachment, including attachment to a prosthetic device.
As to claim 2, the peptide sequence used is RGD (see Schedler- abstract).
As to claim 3, Schedler states the saccharide are chemically functionalized for polymerization/coating formation. Schedler states the monosaccharide is functionalized via at least one reactive group that is suitable for polymerization (see 0037 of translation). Dickerson teaches that integrin-binding peptides can be chemically coupled to saccharide matrices through reactive functional groups on the peptides such as amines or other nucleophilic groups. It would have been obvious to one having ordinary skill in the art to incorporate the peptides taught by Dickerson into the polymerizable saccharide coating chemistry of Schedler. One would have been motivated to do so since Schedler teaches functionalized saccharides capable of participating in coating forming reactions and Dickerson teach reactive peptide molecules capable of reacting with saccharide chemistry.
As to claim 5, Dickerson teaches coupling integrin-binding peptides to saccharide matrices through chemical reactions (see abstract, Figs. 1-3, cols. 3-6). It would have been obvious to one having ordinary skill in the art to first create the saccharide coating layer and subsequently react integrin-biding peptides with the saccharide matrix to form the functional layer.
As to claim 4, Schedler and Dickerson fail to teach copolymerization as claimed. Schedler teaches polymerizable saccharide monomers used to form the coating it would have been obvious to modify the peptides of Dickerson with polymerizable or reactive functional groups, so the peptides could participate in the same polymerization reaction as the saccharide components. Such modification would allow copolymerization thereby creating the polymerized coating layer.
As to claim 6, Dickerson teaches coupling integrin-binding peptides to saccharide matrices through chemical reactions (see abstract, Figs. 1-3, cols. 3-6). Dickerson fails to teach successive reactions of peptides functionalized with reactive groups with saccharides functionalized with polymerizable groups as claimed. Reversing the order of sequential functionalization steps would have been an obvious variation of surface modification technique. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946).
As to claim 8, the saccharides are monosaccharides (see 0031 of Schedler).
As to claim 9, Schedler states the saccharides in their non-functional form is a sugar alcohol (see 0034).
As to claims 10, 22, and 24, the saccharide has polymerizable groups that comprise reactive multiple bonds such as vinyl and allyl groups (See 0037).
As to claims 12, 13, and 23 the coating comprises a carrier layer located on the substrate (see 0032 of Scheler – translation) where the carrier layer has an adhesion promoter (see 0032). The functional layer is bonded to the carrier layer (see 0032). The adhesion promoter is a silane compound (see 0032).
As to claim 14, Schedler et al. states the bonds between the carrier and the substrate is a covalent bond (see 0032).
As to claim 16, the medical product can be formed of a metal such as nickel, titanium, platinum, iridium, gold, cobalt, etc. (See 0017 of translation – Schedler).
As to claim 17, the medical product can be formed of a plastic material such as polyamides, PTFE, ePTFE, polyolefins, etc. (See 0018)
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schedler et al. (WO 2018/210989) in view of Dickerson (US 5677276) as applied to claim 1 above, and further in view of Willis et al. (US 2009/0317443).
The teachings of Schedler et al. and Dickerson as applied to claim 1 are as stated above.
Schedler et al. and Dickerson fail to teach layer is created by polymerization of polymerizable molecules carrying a saccharide unit and a peptide unit as required by claim 7.
Schedler et al. teaches saccharide-based coatings having polymerizable saccharide chemistry where the coating is formed via polymerization. Dickerson teaches saccharide-peptide conjugates where the peptide has integrin binding motifs.
Willis et al. discloses a coated implant coated with a primer and a biocompatible polymer that forms a covalent bond with the primer layer (see abstract). Willis et al. teaches the coating is obtained by polymerizing monomers that include functional pendant groups (see 0026) such as reactive double bonds (acrylates, methacrylates).
It would have been obvious to one having ordinary skill in the art at the time of the invention to modify the saccharide-peptide molecules of Schedler modified by Dickerson et al. to include polymerizable functionality as taught by Willis et al. One would have been motivated to do so since in order to obtain a stable bioactive saccharide based functional layer having integrin-binding activity.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schedler et al. (WO 2018/210989) in view of Dickerson (US 5677276) as applied to claim 1 above, and further in view of Joner et al. (US 2009/0053280).
The teachings of Schedler et al. and Dickerson are as applied to claim 1 above.
Schedler et al. and Dickerson fail to teach the spacer between the polymerizable groups and the peptide as required by claim 15.
Joner et al. discloses a medical device (stent- see abstract), that has a coating where the coating has chemical entity having the formula P-S-A where P represents integrin selective peptide; S is a spacer (organic spacer); and A represents an anchor (see 0052-55). The coating prevents restenosis (see 0005- functional layer). Joner et al. states the spacer is positioned between the peptide and the anchor and is any molecule that allows the integrin selective peptide to bond to integrin (see 0072). The anchor is any component that is capable of binding to the surface of a base metal stent (see 0083). Joner teaches molecules having polymerizable groups such as acrylates, attachment of bioactive ligands to the polymerizable groups and polymerization of the molecules to form functional coating layers.
It would have been obvious to one having ordinary skill in the art to modify Schedler et al. and Dickerson to incorporate the space taught by Joner et al. One would have been motivated to do so since both are directed to coating medical devices with coatings having peptide sequences with integrin-binding motifs, where Joner et al. further teaches the uses of spacers between the anchor material (bound to the medical product) and the peptide in order to improve ligand accessibility (see 0072).
Response to Arguments
Applicant's arguments filed 07/13/2026 have been fully considered but they are not persuasive. Applicant argues that Schedler and Dickerson have opposite teachings because Schedler prevents cellular adhesion whereas Dickerson promotes cellular adhesion. Schedler does not teach the prevention of all cell interaction with the coated medical device. The biological response of Schedler is related to thrombocyte/platelet adhesion and aggregation. Schedler’s testing measures adhesion of CD61-positive platelets. Applicant therefore reads Schedler too broadly in characterizing it as teaching that no cellular attachment of any type is permissible.
Dickerson teaches controlled interaction of RGD-containing peptides with integrin receptors. Dickerson explains tha the effect depends upon presentation of the RGD peptide. RGD containing peptides may inhibit binding of cells such as fibronectin and fibrinogen, wherein RGD-containing peptides presented on a substrate may promote attachment of cells to the substrate such as in a coating of a prosthetic device.
Schedler’s teaching of reduced thrombocyte/platelet adhesion does not show that the use of an immobilized integrin-binding peptide for controlling other cell surface interactions is incompatible with Schedler’s medical device coating.
Applicant further argues that the proposed modification would defeat the intended purpose of Schedler because Schedler relies upon protein repulsion and the absence or reduction of suitable binding proteins at the surface. This argument is not persuasive because Applicant has not established that incorporation of the claimed peptide sequence necessarily eliminates Schedler’s platelet-resistant characteristics or causes increased thrombocyte adhesion or aggregation.
Applicant’s argument concerning would healing is also not persuasive. Although Dickerson describes wound healing and tissue regeneration embodiments, Dickerson teaches the use of RGD beyond a wound matrix, including coating prosthetic device to promote cell attachment. Dickerson is therefore relied upon for its broader teaching concerning the use of RGD-containing peptides to provide integrin-mediated interaction at a biomaterial or prosthetic device surface and for conjugating such peptides with saccharide polymers.
Applicant’s argument that Dickerson is non-analogous art is also not persuasive. Dickerson teaches RGD functionalized biomaterials and prosthetic device surfaces are pertinent to modifying the biological interaction of a functional coating on a medical device. The fact Dickerson additionally describes wound-healing applications does not negate those teachings.
Applicant further argues that there would have been no reasonable expectation of success. Dickerson teaches both conjugation of the RGD containing peptide with saccharide polymers and presentation of the peptides at surfaces to promote cellar attachment. Applicant had not presented evidence showing that the incorporation of such functionality into Schedler’s layer would prevent the resulting coating form performing the claimed function.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CACHET I. PROCTOR/
Examiner
Art Unit 1712
/CACHET I PROCTOR/Primary Examiner, Art Unit 1712
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