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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/19/2025 has been entered.
Claims Status
Claims 1 and 3-11 are pending. Claim 1 is amended.
Response to Amendment /Argument
Applicant's arguments and claim amendment filed 12/19/2025 with respect to (1) the rejection of present claim(s) 1, 7 and 11 under 35 U.S.C. 103 as being unpatentable over WO 2010/059280 to David et al. (“David”) in view of Sanchez et al. (entitled “Alendronate-Functionalized Poly(2-oxazoline)s with Tunable Affinity for Calcium Cations”, Biomacromolecules, 2019; “Sanchez”), and (2) with respect to the rejection of present claims 2 and 4-5 under 35 U.S.C. 103 as being unpatentable over David in view of Sanchez as applied to claim 1 above, further in view of WO 2007/063820 to Kazuyoshi et al. (“Kazuyoshi”), and (3) with respect to rejection of present claim(s) 1 and 3-11 under 35 U.S.C. 103 as being unpatentable over WO 2013/137736 to Bender et al. (“Bender”) in view of Roberts et al. (US 6,436,386, “Roberts”) have been carefully studied, and fully considered but they are not found persuasive for at least the following reasons.
Applicant contends that (1) the cited references does not teach a biocompatible, flexible, bone-adhesive sheet as instantly claimed in instant claim 1 having the following limitations (see Remarks, page 4, last para, to page 5, first para).
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In response to contention (1), Applicant's arguments have been carefully studied and fully considered but they are not found persuasive. The examiner disagrees with applicant’s characteristic and interpretations of instant claim 1. In the present, it is noted that claim 1 is amended to remove the non-elected species (ii), in particular, to remove the following recitations “… or (ii) a plurality of reactive particles comprising an electrophilically activated water soluble polymer and a plurality of bisphosphonate particles comprising nitrogenous bisphosphonate”. The recitation of “the electrophilically activated water-soluble polymer” of instant claim 1 is part of the previously recited non-elected species (ii), and is not a limitation required by instant claim 1, contrary to applicant’s assertion.
Applicant contends that (2) David teaches “fibrous tissue sealant in the form of an anhydrous fibrous sheet having a first component that is a fibrous polymer containing electrophilic or nucleophilic groups and a second component that is capable of crosslinking the first component when the sheet is exposed to an aqueous medium, thereby forming a crosslinked hydrogel that is adhesive to biological tissue…” (remarks, page 5, second para). Per applicant, in David, the reactive groups described therein are intended to bond with one another due to the interaction with free amine groups on the tissue, and thus, there is no motivation to replace the amine-binding moieties of David with calcium binding moieties of Sanchez (remarks, page 5, second and third para).
In response to contention (2), Applicant's arguments have been carefully studied and fully considered but they are not found persuasive for at least the following reasons.
The examiner disagrees with applicant’s characteristic of David. As an initial matter, there is no dispute that David teaches a fibrous sheet having a first component that is a fibrous polymer containing electrophilic or nucleophilic groups and a second component that is capable of crosslinking the first component. While David teaches a fibrous adhesive system with water compatible polymer components having selectable functionalities, David does not teach or require the amine-reactive groups be the sole mechanism of adhesion, contrary to applicant’s assertion.
In response to applicant's argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). MPEP 2141.
In this case, David teaches the inclusion of water-soluble polymer (page 17, lines 16-31, and page 18, lines 1-20). However, David does not specifically teach the inclusion of a water-soluble polymer specifically comprising a calcium-binding polymer, said water-soluble calcium-binding polymer carrying at least one calcium-binding group, wherein the water-soluble calcium-binding polymer is a polyoxazoline, as instantly claimed.
Sanchez teaches alendronate-functionalized polyoxazoline with calcium-binding capacity, and Sanchez teaches the alendronate-functionalized polyoxazoline polymers with their strong and tunable affinity for calcium cations render these polyoxazoline polymers promising candidates for various biomedical applications (abstract, page 2913, left column). Sanchez further teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
It would have been obvious to one of ordinary skill in the art to modify the sheet of David in view the teachings of Sanchez, to select the water-soluble calcium-binding alendronate-functionalized polyoxazoline as taught by Sanchez, to provide an improved biocompatible, flexible, adhesive sheet that is capable of binding to, or otherwise exhibiting a strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue as taught by Sanchez, which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. There would be reasonable expectation of success for such modification since Sanchez teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
Applicant contends that (3) Bender is directed to a biocompatible medical comprising a covalently cross-linked, polymer that is obtained by reacting a nucleophilically activated polyoxazoline (NU-POX) with an electrophilic cross-linking agent other than an electrophilically activated polyoxazoline (EL-POX). The objective of Bender is to have co-reactive components. There is no suggestion to replace a portion of the reactive groups with functional groups that bind to calcium agents rather than being capable of reacting with the corresponding reactive component (remarks, page 5, last para).
In response to contention (3), Applicant's arguments have been carefully studied and fully considered but they are not found persuasive for at least the following reasons.
The examiner disagrees with applicant’s characteristic of Bender.
As an initial matter, there is no dispute that Bender teaches a biocompatible medical product comprising a covalently cross-linked, polymer that is obtained by reacting co-reactive components. However, the teaching of Bender is not limited to a single reaction scheme, indeed, Bender broadly teaches a polyoxazoline-based polymer having selectable substitution of functional groups as desired to achieve desired properties/adhesion properties.
In response to applicant's argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). MPEP 2141.
In this case, Bender teaches the inclusion of suitable electrophilically activated water-soluble polymer (page 6, line 25-33, page 7 lines 1-16, page 20, lines 24-34, and page 21, lines 12, page 20, lines 5-10). However, Bender does not specifically teach the inclusion of a water-soluble polymer specifically comprising a calcium-binding polymer, said water-soluble calcium-binding polymer carrying at least one calcium-binding group, wherein the water-soluble calcium-binding polymer is a polyoxazoline, as instantly claimed.
Sanchez teaches alendronate-functionalized polyoxazoline with calcium-binding capacity, and Sanchez teaches the alendronate-functionalized polyoxazoline polymers with their strong and tunable affinity for calcium cations render these polyoxazoline polymers promising candidates for various biomedical applications (abstract, page 2913, left column). Sanchez further teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
It would have been obvious to one of ordinary skill in the art to modify the sheet of Bender in view the teachings of Sanchez, to select the water-soluble calcium-binding alendronate-functionalized polyoxazoline as taught by Sanchez, to provide an improved biocompatible, flexible, adhesive sheet that is capable of binding to, or otherwise exhibiting a strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue as taught by Sanchez, which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. There would be reasonable expectation of success for such modification since Sanchez teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
Any rejections and/or objections, made in the previous Office Action, and not repeated in the present Office Action, are hereby withdrawn.
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.
Claims 1 and 3-11 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant claim 1 includes the recitation that "the electrophilically activated water-soluble polymer is a polyoxazoline" in lines 11-12. There is insufficient antecedent basis for this limitation in the claim. It is noted that claim 1 is amended to remove the non-elected species (ii), in particular, to remove the following recitations “… or (ii) a plurality of reactive particles comprising an electrophilically activated water soluble polymer and a plurality of bisphosphonate particles comprising nitrogenous bisphosphonate”. The recitation of “the electrophilically activated water-soluble polymer” of instant claim 1 is part of the previously recited non-elected species (ii), and is not a limitation required by instant claim 1, and such recitation should be removed for clarity. For purpose of examination, the examiner considers that claim 1 does not recite or require the inclusion of such “electrophilically activated water-soluble polymer”. Claims 3-11 are rejected due to their dependency of claim 1.
Appropriate correction and clarification are required.
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.
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, 4-7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010/059280 to David et al. (“David”) in view of Sanchez et al. (entitled “Alendronate-Functionalized Poly(2-oxazoline)s with Tunable Affinity for Calcium Cations”, Biomacromolecules, 2019; “Sanchez”) and WO 2007/063820 to Kazuyoshi et al. (“Kazuyoshi”).
Regarding claim 1, David teaches a biocompatible, flexible, bone-adhesive sheet comprising (page 8, lines 18-29, the biocompatible, flexible, fibrous sheet suitable as tissue adhesive for various medical applications):
- a cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space (page 8, line 30, page 13, lines 8-30, page 25, lines 20-31, page 28, lines 1-9, the first component/carrier structure of David that is of fibrous polymer, prepared by spinning method such as electro-spinning, which is the same method as that of the instant application for the carrier structure comprising a three-dimensional interconnected interstitial space, see instant specification, para [0068], i.e., produced by electrospinning, etc.); and
- distributed within the interstitial space, (i) a plurality of polymer particles comprising a water-soluble polymer (page 17, lines 16-31, and page 18, lines 1-20, the second component of polymer having electrophilic groups is distributed within the interstitial space of the first component).
David teaches the inclusion of water-soluble polymer (page 17, lines 16-31, and page 18, lines 1-20). However, David does not specifically teach the inclusion of a water-soluble polymer specifically comprising a calcium-binding polymer, said water-soluble calcium-binding polymer carrying at least one calcium-binding group, wherein the water-soluble calcium-binding polymer is a polyoxazoline, as instantly claimed.
Sanchez teaches alendronate-functionalized polyoxazoline with calcium-binding capacity, and Sanchez teaches the alendronate-functionalized polyoxazoline polymers with their strong and tunable affinity for calcium cations render these polyoxazoline polymers promising candidates for various biomedical applications (abstract, page 2913, left column). Sanchez further teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
It would have been obvious to one of ordinary skill in the art to modify the sheet of David in view the teachings of Sanchez, to select the water-soluble calcium-binding alendronate-functionalized polyoxazoline as taught by Sanchez, to provide an improved biocompatible, flexible, adhesive sheet that is capable of binding to, or otherwise exhibiting a strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue as taught by Sanchez, which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. There would be reasonable expectation of success for such modification since Sanchez teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
As discuss above, David teaches the inclusion of cohesive fibrous carrier structure, but David does not specifically teach the mean diameter of the fibres in the fibrous carrier structure, as instantly claimed.
It is noted that David teaches its carrier structure of fibrous polymer is prepared by spinning method such as electro-spinning (page 8, line 30, page 13, lines 8-30, page 25, lines 20-31, page 28, lines 1-9, the first component/carrier structure of David that is of fibrous polymer, prepared by spinning method such as electro-spinning), which is the same method as that of the instant application for the carrier structure comprising a three-dimensional interconnected interstitial space, see instant specification, para [0068], i.e., produced by electrospinning).
Kazuyoshi teaches biocompatible material having biocompatible nano- or microfiber nonwoven fabric formed by electrospinning method (para [0001]). Kazuyoshi teaches electrospinning method producing fiber having suitable diameter of 1 µm or more and less than 1 mm (para [0009]), which range overlaps with the instantly claimed range of mean diameter of 1-500 µm. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art to modify the sheet of David in view the teachings of Kazuyoshi, to select and include the fibres in the fibrous carrier structure with suitable diameter such as those taught by Kazuyoshi made via electrospinning method (as discussed above, having fiber diameter overlaps with the instantly claimed range), which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. The selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination. See MPEP 2144.05.
Regarding claim 4, modified David does not specifically teach the fibrous carrier structure has the claimed mean thickness.
Kazuyoshi teaches biocompatible material having biocompatible nano- or microfiber nonwoven fabric formed by electrospinning method (para [0001]). Kazuyoshi teaches electrospinning method producing fiber having suitable diameter of 1 µm or more and less than 1 mm (para [0009]). Kazuyoshi teaches suitable thickness of the fibrous carrier structure i.e., the biocompatible nonwoven fabric, is about 100 to 1000 µm, 0.1 to 1 mm (para [0020 on page 6), which range overlaps with the instantly claimed mean thickness range of 0.1-25 mm. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art to modify the modified sheet of David in view the teachings of Kazuyoshi, to select and include the fibrous carrier structure with suitable thickness such as those taught by Kazuyoshi (as discussed above), which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. The selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination. See MPEP 2144.05.
Regarding claim 5, modified David does not specifically teach the fibrous carrier structure has the claimed density.
Kazuyoshi teaches biocompatible material having biocompatible nano- or microfiber nonwoven fabric formed by electrospinning method (para [0001]). Kazuyoshi teaches electrospinning method producing fiber having suitable diameter of 1 µm or more and less than 1 mm (para [0009]). Kazuyoshi teaches suitable thickness of the fibrous carrier structure i.e., the biocompatible nonwoven fabric, is about 100 to 1000 µm, 0.1 to 1 mm (para [0020 on page 6). Kazuyoshi teaches the fibrous carrier structure has high porosity of about 95%, i.e., low bulk density (para [0022]). Kazuyoshi teaches the shape, size, porosity, density, thickness of the fibrous carrier structure i.e., the biocompatible nonwoven fabric, can be realized/controlled as desired by appropriately setting conditions in the electrospinning process (para [0024]).
It would have been obvious to one of ordinary skill in the art to modify the modified sheet of David in view the teachings of Kazuyoshi, to select and include the fibrous carrier structure with suitable density as taught by Kazuyoshi (as discussed above). It would have been obvious to a person of ordinary skill in the art at the time of the invention to adjust the density through routine experimentation in order to achieve the desired properties (i.e., flexibility, compressive strength, and/or easier to deform or compress, etc.) of the fibrous carrier structure of the bone-adhesive sheet once produced, which would have arrived at a workable density that falls within the broad range as instantly claimed, i.e., less than 1 g/cm3. It has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Regarding claim 6, David teaches its fibrous carrier structure is of fibrous fiber-forming polymer and prepared by spinning method such as electro-spinning (page 8, line 30, page 13, lines 8-30, page 25, lines 20-31, page 28, lines 1-9, the first component/carrier structure of David), and David teaches the such suitable materials includes polyvinyl alcohol, i.e., 100% fiber containing polyvinyl alcohol (page 9, lines 20-25, page 27, lines 17-18), meeting the claimed material limitation.
Regarding claims 7 and 11, Sanchez teaches water-soluble alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are calcium-binding polymer of which the calcium binding groups include bisphosphonate (BP/ bisphosphonate groups such as alendronate (Ale) , page 2913, left column, second para, and page 2914, left column, first para), meeting the claimed material limitation of claims 7 and 11.
It would have been obvious to one of ordinary skill in the art to modify the sheet of David in view the teachings of Sanchez, to select the water-soluble calcium-binding alendronate-functionalized polyoxazoline of which the calcium binding groups include bisphosphonate as taught by Sanchez, to provide an improved biocompatible, flexible, adhesive sheet that is capable of binding to, or otherwise exhibiting a strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue as taught by Sanchez, which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. There would be reasonable expectation of success for such modification since Sanchez teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
Claim(s) 1 and 3-11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2013/137736 to Bender et al. (“Bender”) in view of Roberts et al. (US 6,436,386, “Roberts”) and WO 2007/063820 to Kazuyoshi et al. (“Kazuyoshi”).
Regarding claim 1, Bender teaches biocompatible medical products having excellent implant and sealing characteristics and combine cohesiveness with adhesiveness (page 1, lines 5-15, page 19, lines 15-25) and in particular, Bender teaches the medical product may be produced in the form of fibers or a fibrous fleece (page 20, lines 20-30). Bender teaches a biocompatible, flexible, bone-adhesive sheet comprising a carrier having the polymer particles are distributed thereof (see page 16, line 18 to page 17, line 8; page 19, line 25 to page 20, line 4; page 24, lines 9-29), in particular, the carrier comprising a three- dimensional interconnected interstitial space (page 20, lines 5-10, i.e., the carrier is preferably a biodegradable three-dimensional bioresorbable porous structure with attaching properties to bone material and appropriate mechanical properties to guide cellular attachment and subsequent tissue formation); and
- distributed within the interstitial space of the carrier are a plurality of reactive particles comprising an electrophilically activated water-soluble polymer and a plurality of bisphosphonate particles comprising nitrogenous bisphosphonate (page 6, line 25-33, page 7 lines 1-16, page 20, lines 24-34, and page 21, lines 12, page 20, lines 5-10, i.e., the carrier is preferably a biodegradable three-dimensional bioresorbable porous structure with attaching properties to bone material and appropriate mechanical properties to guide cellular attachment and subsequent tissue formation).
Bender teaches the inclusion of suitable electrophilically activated water-soluble polymer (page 6, line 25-33, page 7 lines 1-16, page 20, lines 24-34, and page 21, lines 12, page 20, lines 5-10). However, Bender does not specifically teach the inclusion of a water-soluble polymer specifically comprising a calcium-binding polymer, said water-soluble calcium-binding polymer carrying at least one calcium-binding group, wherein the water-soluble calcium-binding polymer is a polyoxazoline, as instantly claimed.
Sanchez teaches alendronate-functionalized polyoxazoline with calcium-binding capacity, and Sanchez teaches the alendronate-functionalized polyoxazoline polymers with their strong and tunable affinity for calcium cations render these polyoxazoline polymers promising candidates for various biomedical applications (abstract, page 2913, left column). Sanchez further teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
It would have been obvious to one of ordinary skill in the art to modify the sheet of Bender in view the teachings of Sanchez, to select the water-soluble calcium-binding alendronate-functionalized polyoxazoline as taught by Sanchez, to provide an improved biocompatible, flexible, adhesive sheet that is capable of binding to, or otherwise exhibiting a strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue as taught by Sanchez, which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. There would be reasonable expectation of success for such modification since Sanchez teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
As discuss above, Bender teaches the inclusion of cohesive fibrous carrier structure. However, Bender does not specifically teach the mean diameter of the fibres in the fibrous carrier structure. It is noted that Bender teaches its carrier structure of fibrous polymer is prepared by spinning method such as electro-spinning (page 20, lines 21-23), which is the same method as that of the instant application for the carrier structure comprising a three-dimensional interconnected interstitial space, see instant specification, para [0068], i.e., produced by electrospinning).
Kazuyoshi teaches biocompatible material having biocompatible nano- or microfiber nonwoven fabric formed by electrospinning method (para [0001]). Kazuyoshi teaches electrospinning method producing fiber having suitable diameter of 1 µm or more and less than 1 mm (para [0009]), which range overlaps with the instantly claimed range of mean diameter of 1-500 µm. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art to modify the sheet of Bender in view the teachings of Kazuyoshi, to select and include the fibres in the fibrous carrier structure with suitable diameter such as those taught by Kazuyoshi made via electrospinning method (as discussed above, having fiber diameter overlaps with the instantly claimed range), which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. The selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination. See MPEP 2144.05.
Regarding claim 3, Bender teaches the fibrous carrier structure has a felt structure (page 20, lines 20-30, a fibrous fleece).
Regarding claim 4, modified Bender does not specifically teach the fibrous carrier structure has the claimed mean thickness.
Kazuyoshi teaches biocompatible material having biocompatible nano- or microfiber nonwoven fabric formed by electrospinning method (para [0001]). Kazuyoshi teaches electrospinning method producing fiber having suitable diameter of 1 µm or more and less than 1 mm (para [0009]). Kazuyoshi teaches suitable thickness of the fibrous carrier structure i.e., the biocompatible nonwoven fabric, is about 100 to 1000 µm, 0.1 to 1 mm (para [0020 on page 6), which range overlaps with the instantly claimed mean thickness range of 0.1-25 mm. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art to modify the modified sheet of Bender in view the teachings of Kazuyoshi, to select and include the fibrous carrier structure with suitable thickness such as those taught by Kazuyoshi (as discussed above), which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. The selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination. See MPEP 2144.05.
Regarding claim 5, modified Bender does not specifically teach the fibrous carrier structure has the claimed density.
Kazuyoshi teaches biocompatible material having biocompatible nano- or microfiber nonwoven fabric formed by electrospinning method (para [0001]). Kazuyoshi teaches electrospinning method producing fiber having suitable diameter of 1 µm or more and less than 1 mm (para [0009]). Kazuyoshi teaches suitable thickness of the fibrous carrier structure i.e., the biocompatible nonwoven fabric, is about 100 to 1000 µm, 0.1 to 1 mm (para [0020 on page 6). Kazuyoshi teaches the fibrous carrier structure has high porosity of about 95%, i.e., low bulk density (para [0022]). Kazuyoshi teaches the shape, size, porosity, density, thickness of the fibrous carrier structure i.e., the biocompatible nonwoven fabric, can be realized/controlled as desired by appropriately setting conditions in the electrospinning process (para [0024]).
It would have been obvious to one of ordinary skill in the art to modify the modified sheet of Bender in view the teachings of Kazuyoshi, to select and include the fibrous carrier structure with suitable density as taught by Kazuyoshi (as discussed above). It would have been obvious to a person of ordinary skill in the art at the time of the invention to adjust the density through routine experimentation in order to achieve the desired properties (i.e., flexibility, compressive strength, and/or easier to deform or compress, etc.) of the fibrous carrier structure of the bone-adhesive sheet once produced, which would have arrived at a workable density that falls within the broad range as instantly claimed, i.e., less than 1 g/cm3. It has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Regarding claim 6, Bender teaches the carrier structure could be in the form of fibers (page 20, lines 20-30, fibres), and Bender teaches the suitable materials for the fibrous carrier structure includes cellulose, dextran, among others, i.e., 100% fibers of cellulose and/or dextran (page 19, lines 25-34 and page 20, lines 20-30), meeting the claimed material limitation.
Regarding claims 7 and 11, Sanchez teaches water-soluble alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are calcium-binding polymer of which the calcium binding groups include bisphosphonate (BP/ bisphosphonate groups such as alendronate (Ale) , page 2913, left column, second para, and page 2914, left column, first para), meeting the claimed material limitation of claims 7 and 11.
It would have been obvious to one of ordinary skill in the art to modify the sheet of Bender in view the teachings of Sanchez, to select the water-soluble calcium-binding alendronate-functionalized polyoxazoline of which the calcium binding groups include bisphosphonate as taught by Sanchez, to provide an improved biocompatible, flexible, adhesive sheet that is capable of binding to, or otherwise exhibiting a strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue as taught by Sanchez, which would have predictably arrived at a satisfactory adhesive sheet that is the same as instantly claimed. There would be reasonable expectation of success for such modification since Sanchez teaches alendronate-functionalized polyoxazoline that are calcium-binding alendronate-functionalized polyoxazoline and are water-soluble calcium-binding polymer (page 2914, left column, first para) with a strong capacity for self-healing and excellent biocompatibility suitable for various biomedical applications, Sanchez teaches using alendronate-functionalized for their strong binding affinity for calcium cations as present in calcium phosphate nanocrystals, the major component of bone tissue (page 2913, left column and page 2916, left column, first para, page 2920, left column).
Regarding claim 8, Bender teaches the fibrous carrier structure contains about at least 25% of the polymer particles, preferably 50 to 100% of the polymer particles (page 16, lines 13-17, page 20, lines 4-5), which range overlaps with the instantly claimed range of 5 to 90%. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Regarding claim 9, Bender teaches the fibrous carrier structure contains about at least 25% of the polymer particles, preferably 50 to 100% of the polymer particles (page 16, lines 13-17, page 20, lines 4-5), which range overlaps with the instantly claimed range of at least 10%. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Regarding claim 10, Bender teaches the suitable polymer articles has a weighted mean diameter of 0.01 to 1000 µm (page 23, lines 25-30), which range overlaps with the instantly claimed range of 10 to 100 µm. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Conclusion
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/YAN LAN/Primary Examiner, Art Unit 1782