DETAILED ACTION
Claims 1-20 are currently pending. Claims 1-12 are currently under examination.
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 .
Examiner’s Note
Applicant's amendments and arguments filed 10/20/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 10/20/2025, it is noted that claims 1-12 has been amended and no new matter or claims have been added.
New Rejections/Objections:
The following rejections have been newly applied based on Applicant’s claim amendments.
Claim Objections
Claim 6 is objected to because of the following informalities: Claim 6 contains a period after volume. A period should be found only once at the end of a claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 contains the limitation of “polymerizable reactive groups” and additionally contains the limitation of “the polymerizable active group”. It is unclear if the “reactive group” and the “active group” are intended to be the same group and lacks antecedent basis by not using the same language or if the active group and the reactive group are separate groups.
Claim 1 contains the limitation of “wherein the zwitterion has a specific structure as below” wherein multiple zwitterionic structures are listed and no conjunction is used. The lack of conjunction in the claim leads to unclear metes and bounds as it is unclear of if all structure is required “and”, it is in the alternative “or”, or there may be a combination used “and/or”.
Claim 2 contains the limitation “wherein the biological tissue introduced with the reactive group is added to a zwitterionic solution”. Instant claim 1 has been amended to recite active group grafted onto the biological tissue. It is unclear if the recitation of biological tissue and reactive group in claim 2 are before or after grafting.
Claims 3 and 10 recite the limitation “the biological material” in the last line, which does not have clear antecedent basis to the anticoagulant biological material.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) 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 as of the effective filing date of the later invention 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(s) 1-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Guo (previously applied) in view of US 2016/0263278 (previously applied) and US 2009/0155335.
Regarding claim 1, the limitation of a method for preparing a biological material, comprising following steps: introducing, on a biological tissue, a polymerization reactive group and conducting free radical copolymerization is met by Guo teaching bioprosthetic heart valves (BHVs) with radical polymerization-crosslinking method to improve extracellular matrix stability. Porcine pericardium (PP) tissue was decellularized, functionalized with methacryloyl groups and subsequently crosslinked by radical polymerization. Improved the stability is taught (abstract). Porcine pericardium methacryloyl was obtained by decellularized PP was blotted dry and then immersed in deionized water. MA was added dropwise into the tissue at 4 degrees C with a vigorous stirring and washed (page 45, second column, 2.3). Crosslinking is taught.
Regarding claims 2, 7 and 11, Guo teaches APS (ammonium persulfate) is present in a solution at 50 mM for 24 hours at 37 degrees C, the resulting crosslinked PPs were rinsed and treated with Glut (50 mM) at room temperature for 7 days (page 45, second column, 2.4).
Regarding claim 3, the limitation of wherein the biological tissue introduced with the reactive group is added to solution and soaked at 35 to 40 degrees C, an initiator is added to initiate the polymerization to obtain the biological material is met by Guo teaches APS (ammonium persulfate) is present in a solution at 50 mM for 24 hours at 37 degrees C, the resulting crosslinked PPs were rinsed and treated with Glut (50 mM) at room temperature for 7 days (page 45, second column, 2.4).
Regarding claim 4-6, the limitation of wherein the biological tissue is soaked in deionized water, and then the reactive group is added to provide a concentration of the reactive group is 3 to 10% by volume is met by porcine pericardium methacryloyl was obtained by decellularized PP was blotted dry and then immersed in deionized water. MA was added dropwise into the tissue at 4 degrees C with a vigorous stirring where the reaction is continued to 24 hours at 20-25 degrees C and washed (page 45, second column, 2.3). Concentrations of Ma:PP is taught to be 0.04, 0.2, 1.0 and 5.0 (page 45, second column, 2.3). As MPEP 2144.05 recites “where 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 optimization”.
Regarding claim 8, the limitation of wherein the biological tissue is pericardium is met by the Guo teaches porcine pericardium (abstract).
Regarding clam 9, the limitation of wherein the reactive group is methacrylic anhydride is met by Guo teaching methacryloyl (page 45, second column, 2.3).
Regarding claim 12, the limitation of wherein the initiator is a thermal initiator or a photo initiator is met by Guo teaching ammonium persulfate (page 45, second column, 2.4).
Guo does not specifically teach the claims zwitterion structures (claim 1).
Guo does not specifically teach the zwitterion solution having a final concentration of 20 to 500 mM (claim 2), specifically 500 mM (claim 7) wherein the zwitterion accounts for 1 to 30% by weight based on a total weight of biological material (claim 10).
The ‘278 publication teaches polymers which can be used as tissue supplements which can be used for prevention of adhesion formation (abstract). Figure 14 teaches a zwitterion which provides lubrication and compressive strength (Figure 14). A monomer incorporated into the polymer comprises chemical functionality selected from the group consisting of carboxylic acid, phosphate, phosphonate, ammonium and combinations thereof. Without limitations the monomers can be charged (i.e., a negative or positive charge). A solution of monomers and photo-initiators are first allowed to permeate into the tissue followed by in situ photopolymerization with light trough minimally invasive flexible fiberoptic cable. The monomers polymerize upon exposure to visible light into a hydrogel or polymer that is entangled [0015]. The IPN can change mechanical properties to any parameter so desired by the medical practitioners such a compressive modulus, lubrication, prevention of wear [0016]. The IPN is taught to contain polymerized 2-methacryloyloxyethyle phosphorylcholine (pMPC) (Figure 3). Use of a photo initiator is taught ([0133], [0135]). Explants were incubated for 24 hours in the dark in an aqueous solution containing MPC (20 w/v%), ethylene glycol dimethacrylate, eosin (0.1mM). Explants were removed from solution and irradiated with 514 nm ion laser and rinsed for 2 days [0284]. The polymer comprises a monomer that is charged but has no overall net charge, e.g. the monomer is zwitterionic. In some embodiments the monomer is a betaine. It is known that betaines are neutral chemical compounds with positively charged cationic functional groups such as quaternary ammonium cation and with a negatively charged functional group which as a carboxylate [0068]. The polymer is taught to contain a monomer with betaine [0220] wherein an acrylate backbone is taught [0219].
The ’335 publication teaches agents immobilized on a substrate with activity in relevant biological environment. The molecule structures may include hydrophilic tethers which provide flexibility and resistance to non-specific protein adsorption (abstract). Zwitterionic polymer such as sulfobetaine and carboxybetaine based polymers are highly resistant to protein adsorption, especially media such as plasma and serum [0015]. The zwitterionic compound can be surface modification on devices such as valves [0016] specifically heart valves [0096]. Zwitterionic moieties are taught to have non-fouling properties. Polysulfobetaine methacrylate (SBMA) and polycarboxybetaine methacrylate (CBMA) are non-fouling. These zwitterionic polymer grafted surfaces are highly resistant to nonspecific protein adsorption from plasma and serum, bacterial adhesion, biofilm formation and platelet adhesion. Polycarboxybetaine polymers also exhibit anticoagulant properties [0087]. Graft copolymerization of compounds with vinyl functionality by chemical initiation in the presence of viny monomers is taught [0118]. Growing the polymer on the surface through free radical polymerization is taught though the use of surface functionalization with the same moiety used for polymerization (e.g. vinyl groups for free radical polymerization [0129].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to react CBMA with the methacryloyl porcine pericardium as Guo teaches the desire for extracellular matrix stability though functionalization of porcine tissue and the ‘278 publication teaches improvement of compressive modulus and prevention of wear and improved lubrication and compressive strength through use of betaine monomers and the ‘335 publication specifically teaches CBMA, a betaine, which has anticoagulant properties. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘278 publication teaches polymerization through photopolymerization to tissue and Guo teaches polymerization using photo initiator through radical crosslinking onto tissue and the ‘335 publication teaches grafting onto a surface of a device using free radical polymerization of betaine containing acrylate groups such as CBMA. It would have been prima facie obvious to one of ordinary skill in the art to use CBMA on the methacryloyl porcine treated tissue of Guo as Guo teaches the desire for further treatment for matrix stability and the ‘278 publication teaches specific betaines to be used to treat tissue to obtain the desired functionality such as compressive strength and lubriciously. One of ordinary skill in the art would be motivated to specifically use CMBA as the ‘335 publication teaches the zwitterionic polymer grafted surfaces are highly resistant to nonspecific protein adsorption from plasma and serum, bacterial adhesion, biofilm formation and platelet adhesion with polycarboxybetaine polymers also exhibit anticoagulant properties and use on heart valves wherein Guo teaches a heart valve. It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to optimize the concentration of the zwitterionic compound to obtain the desired porcine pericardium tissue as the ‘278 publication teaches changing the properties to obtain the desired mechanical properties and Guo teaches multiple concentrations thus teaching an optimizable parameter. As MPEP 2144.05 recites “where 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 optimization”.
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); 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.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/666,839 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the ‘839 application are directed to preparation of biological material by treating with methacrylate followed by treatment with 3-[[2-(methacryloyloxy)ethyl]dimethylammonium]propionate (CBMA), wherein the same structure and method steps are taught and thus would have the same anticoagulant properties absent factual evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,097,113. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the ‘113 patent are directed to preparation of a bioprosthetic valve and functional biologic tissue material treated with methacrylamide and CBMA by soaking the tissue in water to obtain a first mixture, adding an active group then performing polymerization with a second mixture containing the MPC, wherein overlapping times and concentrations are taught, thus rendering the method of preparing the biological material obvious. Wherein the same structure and method steps are taught and thus would have the same anticoagulant properties absent factual evidence to the contrary.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
Applicant argues Guo nowhere mentions or attempts to solve the problem of anticoagulation for blood contacting materials. Guo discloses only the homopolymerization of methacryloyl groups that are covalently attached to the tissue rather than copolymerization of methacryoyl groups with other groups let along copolymerization with the zwitterion. The ‘278 publication teaches zwitterionic monomers like MPC however only mentions as a tissue supplement primary to provide lubricity and compressive strength and does not mention anticoagulant properties.
In response, the combination of references teaches the method steps claimed and the specific zwitterionic structure and thus would have the anticoagulant activity absent factual evidence to the contrary. Further newly applied ‘335 publication teaches Polysulfobetaine methacrylate (SBMA) and polycarboxybetaine methacrylate (CBMA) are non-fouling. These zwitterionic polymer grafted surfaces are highly resistant to nonspecific protein adsorption from plasma and serum, bacterial adhesion, biofilm formation and platelet adhesion. Polycarboxybetaine polymers also exhibit anticoagulant properties [0087].
Applicant argues the ‘278 publication discloses an interpenetrating polymer network where the monomers permeate into the tissue followed by in situ photopolymerization and the pMPC is entangled within the tissue matrix. Even when crosslinked, the bonding occurs within the polymer network itself rather than forming a covalent chemical bond with the tissue matrix. A person would have no motivation to combine Guo and the ‘278 publication because they address fundamentally different problems.
In response, Guo teaches heart valve replacements wherein the porcine pericardium tissue is decellularized, functionalized with methacyrloyl groups and subsequently crosslinked by radial polymerization. Thus Guo teaches the modification of tissue with reaction to the functionalized tissue surface. The ‘278 publication teaches the use of zwitterionic for lubrication and compressive strength (Figure 14) wherein the monomers are polymerized [0015] and the polymerized can be used for tissue supplements (abstract). The polymer is taught to contain a monomer with betaine [0220] wherein an acrylate backbone is taught [0219]. The ‘335 publication teaches the zwitterionic compound can be surface modification on devices such as valves [0016] specifically heart valves [0096]. Polysulfobetaine methacrylate (SBMA) and polycarboxybetaine methacrylate (CBMA) are non-fouling. These zwitterionic polymer grafted surfaces are highly resistant to nonspecific protein adsorption from plasma and serum, bacterial adhesion, biofilm formation and platelet adhesion. Polycarboxybetaine polymers also exhibit anticoagulant properties [0087]. Graft copolymerization of compounds with vinyl functionality by chemical initiation in the presence of viny monomers is taught [0118]. Thus it would have been prima facie obvious to one of ordinary skill in the art to use CBMA on the methacryloyl porcine treated tissue of Guo as Guo teaches the desire for further treatment for matrix stability and the ‘278 publication teaches specific betaines to be used to treat tissue to obtain the desired functionality such as compressive strength and lubriciously. One of ordinary skill in the art would be motivated to specifically use CMBA as the ‘335 publication teaches the zwitterionic polymer grafted surfaces are highly resistant to nonspecific protein adsorption from plasma and serum, bacterial adhesion, biofilm formation and platelet adhesion with polycarboxybetaine polymers also exhibit anticoagulant properties and use on heart valves wherein Guo teaches a heart valve.
Applicant argues the test results of the present disclosure demonstrate zwitterion modified tissues have superior and unexpected technical effect compared wot hose modified only with methacrylic anhydride (Guo). The initially grafted reactive groups being short enable only short distance molecular crosslinking. While in the present disclosure long-chain zwitterionic branches are further grafted onto this polymer. Due to their hydrophilic nature these long zwitterionic chins spontaneously arrange to form a hydration layer and have excellent anticoagulant properties of the present tissue.
In response, the anticoagulant effect is not considered unexpected as the ‘335 publication specifically teaches the zwitterionic compound can be surface modification on devices such as valves [0016] specifically heart valves [0096]. Polysulfobetaine methacrylate (SBMA) and polycarboxybetaine methacrylate (CBMA) are non-fouling. These zwitterionic polymer grafted surfaces are highly resistant to nonspecific protein adsorption from plasma and serum, bacterial adhesion, biofilm formation and platelet adhesion. Polycarboxybetaine polymers also exhibit anticoagulant properties [0087]. Thus the anticoagulant effect from surface modification is not considered unexpected.
Double Patenting:
Applicant argues claim 1 has been amended and thus the rejections should be withdrawn.
In response, the double patenting rejections have been modified in view of Applicant’s amendments to instant claim 1.
Conclusion
No claims are allowed.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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