DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Status of the Claims
Claims 1-17 are pending and under consideration in this action.
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.
Claim 1 is 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 recites the limitation "the sulfur content of the anionic polymer" in line 14. There is insufficient antecedent basis for this limitation in the claim because there is no previous mention of a sulfur content or that the anionic polymer is one containing sulfur. It is noted the limitation that the anionic polymer is dextran sulfate is first introduced in line 16.
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.
Claims 1-10 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Biran et al. (Biran) (Advanced Drug Delivery Reviews; available online Dec. 29, 2016) and McKay (US 2014/0135285 A1; published May 15, 2014).
With regards to Claims 1, 4-10, and 14, Biran discloses that blood contact with biomaterials triggers activation of multiple reactive mechanisms that can impair the performance of implantable medical devices and potentially cause adverse clinical events. This includes thrombosis and thromboembolic complications due to activation of platelets and the coagulation cascade, activation of the complement system, and inflammation. Numerous surface coatings have been developed to improve blood compatibility of biomaterials. Biran thus discloses a review of the fundamental principles of non-eluting heparin coatings, mechanisms of action, and clinical applications with focus on those technologies which have been commercialized, with an emphasis on the CARMEDA® BioActive Surface (CBAS® Heparin Surface), a widely used commercialized technology for the covalent bonding of heparin (abstract; p.14, Table 1).
The CARMEDA® BioActive Surface provides heparin covalently bonded by endpoint attachment to a base matrix (p.14, Table 1). The Carmeda heparin binding approach employs a single covalent bond between the reducing end of the heparin molecule and the material substrate. Unfractionated heparin is first partially depolymerized by nitrous acid deamination. The process yields heparin molecules of a reduced molecular weight that contain single reactive aldehyde groups at their reducing terminus. The depolymerized heparin is subsequently covalently bonded by reductive amination to a substrate that contains amine functional groups. The amines are introduced onto the surface by application of base matrix that consists of alternating layers of the anionic polysaccharide dextran sulfate and the cationic polymer polyethyleneimine. As shown in Figure 2, the cationic polymer is the most outer coating layer, and the heparin molecules are end-point attached by covalent bonding to amines in the base matrix. The base matrix can be deposited on diverse types of materials (polymers, metals, glass). The end result is a permanently immobilized, stable, non-leaching coating that is a few hundred nanometers thick (p.16, Fig.2, 4.8. CARMEDA® BioActive Surface (CBAS® Heparin Surface)).
With regards to Claims 13 and 17, Biran discloses that the coating is known to be applied to extracorporeal circulation devices, hemodialysis catheters, ventricular assist devices, vascular grafts, stent-grafts, and peripheral and coronary vascular stents (p.14, Table 1; p.16, 4.8 CARMEDA® BioActive Surface (CBAS® Heparin Surface), para.1; p.19, 9. Performance of CBAS Heparin Surfaces in vivo).
Biran does not appear to explicitly disclose (i) the sulfur content of the anionic polymer (Claims 1 and 14) or (ii) the molecular weight of the anionic polymer (Claims 1-3 and 14-16). McKay is relied upon for these disclosures. The teachings of McKay are set forth herein below.
McKay discloses an implantable device for reducing or preventing adhesion formation at a post-operative tissue site in a patient, wherein the implantable device comprises dextran sulfate (McKay claims 1 and 2).
McKay discloses that dextran is used medicinally as an antithrombotic (anti-platelet) to reduce blood viscosity, and as a volume expander in anemia. The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium, increasing their electronegativity and thus reducing erythrocyte aggregation and platelet adhesiveness (par.0036).
Dextran used in the matrix can have a wide range of average molecular weights from about 1,000 Daltons to about 1,000,000 Daltons. In some embodiments, the dextran can have an average molecular weight of about 1.5 million to about 2.5 million Daltons (para.0037). In some embodiments, the dextran can have an average molecular weight of about 500,000 to about 1,000,000 and more particularly about 500,000 to about 750,000 Daltons (par.0038).
In some embodiments, the dextran comprises dextran sulfate. In some embodiments, the sulfur content of the dextran can be increased, e.g., the number of sulfur groups per glucosyl residue in the dextran chain. The average sulfur content for dextran may be about 10 to 25%, such as 16 to 19%, corresponding to about two sulfate groups per glucosyl residue (para.0039).
As discussed above, Biran discloses that blood contact with biomaterials triggers activation of multiple reactive mechanisms, such as thrombosis and thromboembolic complications, that can impair the performance of implantable medical devices and potentially cause adverse clinical events. Biran discloses that the Carmeda coating, which includes dextran sulfate, is known to be a coating that that was developed to improve blood compatibility of biomaterials. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the teachings of Biran and McKay and use dextran sulfate with a molecular weight and sulfur content as disclosed by McKay (e.g., molecular weights of about 1.5 million to about 2.5 million Daltons, or about 500,000 to about 750,000 Daltons; and about 10 to 25% sulfur content or 16 to 19% sulfur content) as the dextran sulfate in Biran’s Carmeda coating discussed above. One of ordinary skill in the art would have been motivated with a reasonable expectation of success in doing so as both Biran and McKay recognize that thrombotic mechanisms can impair the performance of implantable medical devices, and Biran discloses the use of dextran sulfate in their coating to prevent thrombosis and coagulation, and McKay discloses that dextran sulfates with the aforementioned molecular weights and sulfur contents are known to be used medicinally as an antithrombotic, and known to be suitable for use on implantable devices to reduce or prevent adhesion.
Furthermore, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05.
It is noted that Claim 1 is directed to a product-by-process claim. With regards to the process limitations of Claims 1 and 4-7, Note MPEP 2113: “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The MPEP also indicates that “the structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979).
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Biran et al. (Biran) (Advanced Drug Delivery Reviews; available online Dec. 29, 2016) and McKay (US 2014/0135285 A1; published May 15, 2014) as applied to Claims 1-10 and 13-17 set forth above, further in view of Oscarson et al. (Oscarson) (US 2010/0074938 A1; published Mar. 25, 2010).
The teachings of Biran and McKay and the motivation for their combination as they apply to Claims 1-10 and 13-17 are set forth above and incorporated herein.
The combined teachings of Biran and McKay do not appear to explicitly disclose wherein the anticoagulant is a full length heparin (Claim 11), or wherein the anticoagulant entity is covalently attached via a linker (Claim 12). Oscarson is relied upon for these disclosures. The teachings of Oscarson are set forth herein below.
Oscarson discloses a medical device having a surface which comprises a coating layer, said coating layer being biocompatible composition comprising an anti-coagulant entity capable of interacting with mammalian blood to prevent coagulation or thrombus formation, which entity is covalently attached to said surface through a link comprising a 1,2,3-triazole (abstract; para.0018).
The surface comprises two or more coating layers, with only the outer coating layer being attached to the entity (Oscarson claims 1 and 6). In particular, the outermost layer is a cationic polymer, such as polyamine, covalently attached to the entity (Oscarson claims 7 and 11). An exemplary polyamine is polyethyleneimine (para.0053). To prepare the non-thrombogenic device, the medical device is treated to present a cationic polymer surface layer which has been functionalized to bear alkyne groups. Said cationic polymer surface layer is then reacted with an anti-coagulant entity, such as a heparin moiety, which is functionalized to bear an azido group; thereby attaching the anti-coagulant entity to the device through a link comprising a 1,2,3-triazole (Oscarson claims 20-22; para.0031, 0036-0046).
The preferred anti-coagulant entities are heparin moieties, and especially full length heparin (i.e., native heparin) (para.0022, 0023). Oscarson discloses that it is preferred the heparin moiety is single point attached, preferably end point attached. It is also preferred the end point attached heparin is connected through its reducing end (C1 position). The advantage of end point attachment, especially reducing end point attachment is that it is expected that the biological activity of the heparin moiety is maximized due to enhanced availability of the thrombin interaction sites as compared with attachment elsewhere in the heparin moiety (par.0024).
Oscarson discloses that the link between the heparin moiety and the surface is a non-biodegradable link in order that the coated medical device is non-thrombogenic for a long period of time (para.0028).
With regards to Claims 11 and 12, as discussed above, Biran discloses that blood contact with biomaterials triggers activation of multiple reactive mechanisms, such as thrombosis and thromboembolic complications, that can impair the performance of implantable medical devices and potentially cause adverse clinical events. Biran discloses that in the multi-layered Carmeda coating, heparin is covalently bonded by endpoint attachment to the top cationic polymer (polyethyleneimine). One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to further combine the teachings of Biran and McKay with the teachings of Oscarson and end-point attach full length heparin (native heparin) covalently to the outer polyethyleneimine layer of the coating of the combined teachings of Biran and McKay discussed above via a linker as disclosed by Oscarson. One of ordinary skill in the art would have been motivated with a reasonable expectation of success in doing so as both Biran and Oscarson are directed to multi-layer coatings having heparin covalently bonded thereon for application to medical devices to prevent coagulation or thrombus formation, and Oscarson discloses an art recognized method of covalently attaching heparin at its endpoint to enhance the availability of the thrombin interaction site of the heparin and providing a long duration of non-thrombogenic activity to the medical device.
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
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.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,016,978 B2 (USPN 978) in view of Biran et al. (Biran) (Advanced Drug Delivery Reviews; available online Dec. 29, 2016).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a solid object having a thromboresistant surface which is a layered coating of cationic and anionic polymer, wherein the outer coating layer is the cationic polymer and has covalently attached thereon an anticoagulant entity, such as heparin. Although USPN 978 is directed to a process, the process results in the solid object of the present application.
The primary difference between the instant claims and USPN 978 is that USPN 978 does not appear to explicitly claim what the solid object is, as is recited in the instant claims 13 and 17. Biran is relied upon for this disclosure. The teachings of Biran are set forth above and incorporated herein.
Biran discloses a multilayer coating for medical devices (e.g., Carmeda) to protect against thrombosis that would impair the performance of implantable medical devices and potentially cause adverse clinical events. As USPN 978 is directed to a process of making a coating that would provide thromboresistant surface for solid objects, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the claims of USPN 978 and the teachings of Biran, and apply the method of USPN 978 to Biran’s listed medical devices. One of ordinary skill in the art would have been motivated to do so in order to provide a thromboresistant surface of medical devices, which Biran discloses as being known to be negatively impacted by thrombotic activity. One of ordinary skill in the art would have had a reasonable expectation of success in doing so as Biran discloses that implantable medical devices are known to be applied thereon a thromboresistant coating.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11,850,334 B2 (USPN 334) in view of McKay (US 2014/0135285 A1; published May 15, 2014).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a solid object having a thromboresistant surface which is a layered coating of cationic and anionic polymer, wherein the anionic polymer is dextran sulfate, and wherein the outer coating layer is the cationic polymer and has covalently attached thereon an anticoagulant entity, such as heparin.
The primary difference between the instant claims and the claims of USPN 334 is that the claims of USPN 334 do not appear to explicitly claim the molecular weight and sulfur content of the dextran sulfate. McKay is relied upon for this disclosure. The teachings of McKay are set forth above and incorporated herein.
The claims of USPN 334 are directed to providing an anticoagulant surface comprising a multilayer coating of cationic and anionic polymers wherein the anionic polymer is dextran sulfate. The anticoagulant surface is for application onto medical devices. With regards to the molecular weight of the dextran sulfate and the sulfur content of the dextran sulfate, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the claims of USPN 334 and teachings of McKay and use dextran sulfate with a molecular weight and sulfur content as disclosed by McKay (e.g., molecular weights of about 1.5 million to about 2.5 million Daltons, or about 500,000 to about 750,000 Daltons; and about 10 to 25% sulfur content or 16 to 19% sulfur content) as the dextran sulfate in USPN 334’s claimed coating. One of ordinary skill in the art would have been motivated with a reasonable expectation of success in doing so as both USPN 334 and McKay are directed to providing anticoagulant activity to medical devices, and USPN 334 claims the use of dextran sulfate in their coating for such purposes, and McKay discloses that dextran sulfates with the aforementioned molecular weights and sulfur contents are known to be used medicinally as an antithrombotic, and known to be suitable for use on implantable devices to reduce or prevent adhesion.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,064,978 B2 (USPN 978) in view of McKay (US 2014/0135285 A1; published May 15, 2014).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a solid object having a thromboresistant surface which is a layered coating of cationic and anionic polymer, wherein the anionic polymer is dextran sulfate, and wherein the outer coating layer is the cationic polymer and has covalently attached thereon an anticoagulant entity, such as heparin. Although USPN 978 is directed to a process, the process results in the solid object (e.g., medical device) of the present application.
The primary difference between the instant claims and the claims of USPN 978 is that the claims of USPN 978 do not appear to explicitly claim wherein the anionic polymer is dextran sulfate, and the molecular weight and sulfur content of the dextran sulfate. McKay is relied upon for this disclosure. The teachings of McKay are set forth above and incorporated herein.
The claims of USPN 978 are directed to providing a medical device with a non-thrombogenic coating, which comprising a multilayer coating of cationic and anionic polymers. With regards to the specific anionic polymer, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the claims of USPN 978 and teachings of McKay and use dextran sulfate with a molecular weight and sulfur content as disclosed by McKay (e.g., molecular weights of about 1.5 million to about 2.5 million Daltons, or about 500,000 to about 750,000 Daltons; and about 10 to 25% sulfur content or 16 to 19% sulfur content) as the anionic polymer in USPN 978’s claimed coating. One of ordinary skill in the art would have been motivated with a reasonable expectation of success in doing so as both USPN 978 and McKay are directed to providing non-thrombogenic activity to medical devices, and McKay discloses that dextran sulfates (anionic polymer) with the aforementioned molecular weights and sulfur contents are known to be used medicinally as an antithrombotic, and known to be suitable for use on implantable devices to reduce or prevent adhesion.
Conclusion
Claims 1-17 are rejected. No claims are allowed.
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/MONICA A SHIN/Primary Examiner, Art Unit 1616
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