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 . Claims included in the prosecution are claims 1-4, 7-13, and 16-19.
Applicants' arguments, filed 01/05/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
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.
1. Claims 1, 7-13, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Bender et al. (WO 2016/056901, Apr. 14, 2016) (hereinafter Bender 1) in view of Sehl et al. (US 2010/0233246, Sep. 16, 2010) (hereinafter Sehl) and Bender et al. (US 2015/0045507, Feb, 12, 2015) (hereinafter Bender 2).
Bender 1 discloses a tissue-adhesive haemostatic product coated with an electrophilically activated polyoxazoline (EL-POX) containing at least 2 reactive electrophilic groups, wherein the product is a coated mesh. The porous substrate absorbs body fluids, such as blood (abstract). A mesh (i.e., structure comprising a three-dimensional interconnected interstitial space) is a sheet made from woven or non-woven fibres. The fibres contained in the mesh are preferably made of biocompatible polymers (page 12, lines 22-23). The mesh may contain at least 50% oxidized regenerated cellulose (page 9, lines 14-16). The electrophilic groups present in the EL-POX include carboxylic acid esters, sulfonate esters, phosphonate esters, and combinations thereof (page 8, lines 8-25). An example of EL-POX is star-shaped POX-polymers end-functionalized with NHS-esters (page 8, lines 5-6). The coating may include a nucleophilic cross-linking agent (page 15, lines 27-28). The nucleophilic cross-linking agent preferably contains at least 3 reactive nucleophilic groups (page 16, lines 1-2). Examples of nucleophilic cross-linking agents include nucleophilically activated POX (NU-POX), chitosan, chitosan derivatives, and combinations thereof (page 16, lines 17-19). As noted in the specification on page 22, line 10, NU-POX is poly(2-ethyl/aminoethylamidoethyl-2-oxazoline) copolymer). The EL-POX coating typically represents 5-75% of the haemostatic product (page 19, line 30). The EL-POX coated haemostatic product has excellent adhesive properties due to the presence of electrophilic reactive groups that are capable of reacting with e.g., amine groups that are naturally present in tissue, under the formation of covalent bonds (page 3, line 33-34 – page 4, lines 1-2).
Bender 1 differs from the instant claims insofar as not disclosing wherein the EL-POX and the nucleophilic cross-linking agent are present together in a particle and wherein the particles are distributed within the interstitial space.
However, Sehl discloses a crosslinkable, biocompatible, adhesive composition comprising a hydrophilic polymer, a crosslinkable component A having m nucleophilic groups, and a crosslinkable component B having n electrophilic groups (¶ [0020]). Each of the crosslinkable components may be polymeric. Alternatively, one or two of the crosslinkable components A and B may be a low molecular weight crosslinking agent (¶ [0021]). The crosslinkable composition can be coated on a suitable fibrous material (¶ [0049]). The adhesive composition components may be in dry form when coated on a patch (¶ [0068]). The reactive components may be in powder form (¶ [0071]). A collagen sheet may be impregnated with the crosslinkable composition in powder form (claim 28).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have provided the electrophilically activated polyoxazoline (EL-POX) and the nucleophilic cross-linking agent of Bender 1 as a composition in powder form since this is a known and effective alternate method of providing a coating of electrophilic polymer and nucleophilic crosslinking agent to a fibrous material to form an adhesive product as taught by Sehl.
It would have been prima facie obvious to one of ordinary skill in the art to have coated the interstitial space of the mesh of Bender I with the powders since it is desirable in the art to have sheets impregnated with the electrophilic polymer and nucleophilic crosslinking agent as taught by Sehl.
The combined teachings of Bender 1 and Sehl do not disclose wherein the particles have a diameter of 0.5-100 µm and wherein particles are in the form of an agglomerate comprising electrophilic particles and nucleophilic particles.
However, Bender 2 discloses a kit for producing a biocompatible, cross-linked polymer, said kit comprising a NU-POX and an electrophilic crosslinking agent of claim 33, wherein the kit comprises a powder consisting of particles having a weight averaged mean diameter of 0.01-1000 µm, said particles including particles containing NU-POX and particles containing the electrophilic crosslinking agent (claim 43). The NU-POX and the electrophilically activated cross-linking agent may be contained in the same particles or they may be contained in different particles within the same powder (¶ [0129]).
As discussed above, it would have been obvious to one of ordinary skill in the art to have provided the electrophilically activated polyoxazoline (EL-POX) and the nucleophilic cross-linking agent of Bender 1 as a composition in powder form. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the powders as powder agglomerates comprising particles of EL-POX and particles of the nucleophilic cross-linking agent since containing NU-POX and EL-POX in the same particle is another known and effective alternate method of providing NU-POX and EL-POX particles as taught by Bender 2.
In regards to instant claim 1 reciting wherein the particles have a diameter of 0.5-100 µm, since it was known in the art that electrophilic particles and nucleophilic particles each have a diameter of 0.01-1000 µm as taught by Bender 2, combining the particles would produce a powder with a diameter that overlaps with the claimed range. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. MPEP 2144.05 A.
In regards to instant claim 1 reciting a flexible sheet, since the instant specification discloses on page 10 wherein the claimed fibrous carrier structure comprises at least 50 wt. % oxidized regenerated cellulose and Bender 1 discloses substantially the same fibrous carrier structure, the product of Bender 1 would necessarily be flexible like the claimed invention.
In regards to instant claim 1 reciting a water-resistant fibrous carrier, since the product of Bender 1 absorbs blood and blood comprises mostly of water, it would have been obvious to one of ordinary skill in the art that product of Bender 1 is water-resistant.
In regards to instant claim 1 reciting a cohesive fibrous carrier, Bender 1 discloses a mesh and a mesh is a cohesive.
In regards to instant claim 1 reciting wherein the fibrous carrier structure does not contain a polymer carrying reactive nucleophilic groups or a nucleophilic cross-linking agent containing two or more reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the water-soluble electrophilic polymer, Bender 1 discloses wherein the EL-POX and nucleophilic cross-linking agent are coated on the tissue-adhesive haemostatic product and not wherein they are within the fibers of the mesh. Therefore, the EL-POX and nucleophilic cross-linking agent are not contained in the fibrous carrier structure. In regards to instant claim 1 reciting wherein the particles are present in an amount of at least 3%, this would have been obvious since Bender 1 discloses wherein the coating represents 5-75% of the haemostatic product.
In regards to instant claim 8 reciting wherein the particles comprise at least 10 wt. % of the electrophilic polymer, since Bender 1 discloses wherein EL-POX provides the haemostatic product with excellent adhesive properties, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount based on the level of adhesiveness desired. 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 experimentation. See 2144.05(II)(A).
In regards to instant claim 19, this is a product-by process claim. Even 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. See MPEP 2113. In the instant case, instant claim 19 recite the process of forming the particle agglomerate. As discussed in the rejection, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the powders as powder agglomerates comprising particles of EL-POX and particles of the nucleophilic cross-linking agent from the teachings of Bender 2. Thus, since powder agglomerates would have been obvious from the prior art, the claim is unpatentable even though the prior art does not disclose forming the powder agglomerate in the same manner as recited in instant claim 19.
Response to Arguments
Applicant argues that the substrate in Bender 1 comprises nucleophilic polymer which is in part covalently bonded to the EL-POX group. Conversely, the fibers contained in fibrous carrier structure of the claimed biocompatible, flexible, haemostatic sheet, do not contain a polymer carrying reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the water-soluble electrophilic polymer under the formation of a covalent bond.
The Examiner does not find Applicant’s argument to be persuasive. Bender 1 discloses wherein the coating may include a nucleophilic cross-linking agent. Fibers coated with a nucleophilic cross-linking agent is not the same as fibers containing a nucleophilic cross-linking agent. As evidenced by Merriam-Webster, the term “contain” means to have within. Bender 1 does not disclose wherein the nucleophilic cross-linking agent is within the fibers. Therefore, Bender 1 does not teach a fiber containing a polymer carrying reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the water-soluble electrophilic polymer under the formation of a covalent bond. Furthermore, if coating were to mean the same as containing, the claims would be indefinite. The claims recite a nucleophilic cross-linking agent distributed within the interstitial space. The nucleophilic cross-linking agent must touch the fibers when distributed within the interstitial space in order to have the sheet still comprise of the nucleophilic cross-linking agent and not have the nucleophilic cross-linking agent fall out. Touching the fibers is no different than coating the fibers. As such, coating and containing are not synonymous and Applicant’s argument is unpersuasive.
Applicant argues that Sehl fails to cure the deficiencies of Bender 1 because, like Bender 1, Sehl too discloses a collagen sponge or sheet impregnated with a reactive powder comprising a crosslinkable component A having m nucleophilic groups, and a crosslinkable component B having n electrophilic groups, which react to form covalent bonds.
The Examiner does not find Applicant’s argument to be persuasive. As discussed above, Bender 1 teaches a fibrous carrier structure not containing a nucleophilic cross-linking agent. Furthermore, Sehl does not teach away from the claims. Impregnating means to fill. A sponge has pores. Therefore, a sponge impregnated with the reactive powder would have the sponge filled with the reactive powder in the pores. This is not the same as having fibers containing the reactive powder, which has the reactive powder within the fibers. As such, Sehl does not teach away and Applicant’s argument is unpersuasive.
Applicant argues that the coated mesh/foam/powder and collagen sponges/sheets are not encompassed by the fibrous carrier structure recited in the present claims. Example 1 of the specification shows that in comparison to the fibrous carrier structure of the present invention which contained homogenously dispersed blue NHS-Pox powder, both the gelatin and collagen sponge/foam constructs failed to allow for distribution throughout the construct. Thus, Bender 1 and Sehl fail to teach or suggest distribution of plurality of reactive polymer particles within the interconnected interstitial space of a fibrous carrier structure.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has only compared the claimed invention against a sponge and has not shown wherein the claimed invention is superior over the product of Bender 1, which is a mesh. The claimed invention must be compared with the closest prior art to be effective to rebut a prima facie case of obviousness. See MPEP 716.02(e). The mesh of Bender 1 appears to be the closest prior art since, like the claimed invention, it is a fibrous carrier structure comprising a three-dimensional interconnected interstitial space. As such, Applicant’s argument is unpersuasive.
Applicant argues that Bender 1 prefers using liquid coating solutions. See Example 7 of Bender 1.
The Examiner does not find Applicant’s argument to be persuasive. Bender 1 using a liquid coating in an Example does not mean that Bender 1 teaches away from modifying the coating to be in a different form; especially when Bender 1 does not disclose wherein having a liquid form is required or necessary. As such, Applicant’s argument is unpersuasive.
Applicant argues that there is no evidence that the mere mixture of components in Bender 2 would form an agglomerate.
The Examiner does not find Applicant’s argument to be persuasive. Bender 2 specifically discloses in paragraph [0129] wherein the NU-POX and the electrophilically activated cross-linking agent may be contained in the same particles or they may be contained in different particles within the same powder. When NU-POX and the electrophilically activated cross-linking agent are contained in different particles within the same powder, particles of NU-POX and particles of the electrophilically activated cross-linking agent are mixed to form a powder. When NU-POX and the electrophilically activated cross-linking agent are contained in the same particles, they are agglomerated. An agglomerate is a cluster of disparate elements. Having NU-POX and the electrophilically activated cross-linking agent contained in the same particles is a cluster of disparate elements. As such, Bender 2 does teach agglomerates and Applicant’s argument is unpersuasive.
Applicant argues that the particle agglomerates in the claimed haemostatic powder are formed by wet granulation by wetting the electrophilic polyoxazoline particles with the non-aqueous granulation liquid, followed by combining the wetted polyoxazoline particles with the nucleophilic polymer particles.
The Examiner does not find Applicant’s argument to be persuasive. In regards to instant claim 19, this is a product-by process claim. Even 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. See MPEP 2113. In the instant case, instant claim 19 recite the process of forming the particle agglomerate. As discussed in the rejection, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the powders as powder agglomerates comprising particles of EL-POX and particles of the nucleophilic cross-linking agent from the teachings of Bender 2. Thus, since powder agglomerates would have been obvious from the prior art, the claim is unpatentable even though the prior art does not disclose forming the powder agglomerate in the same manner as recited in instant claim 19. As such, Applicant’s argument is unpersuasive.
Applicant argues that Bender 2 discloses 0.01-1000 µm wight averaged mean diameter for Nu-Pox and an electrophilic cross-linking agent and not for reactive polymer particles containing a water-soluble EL-POX and a nucleophilic cross-linking agent.
The Examiner does not find Applicant’s argument to be persuasive. As discussed in the rejection, since it was known in the art that electrophilic particles and nucleophilic particles each have a diameter of 0.01-1000 µm as taught by Bender 2, combining the particles would produce a powder with a diameter that overlaps with the claimed range. Applicant has not addressed why this wouldn’t make the claim obvious. As such, Applicant’s argument is unpersuasive.
2. Claims 2-4 are rejected under 35 U.S.C. 103 as being unpatentable over Bender et al. (WO 2016/056901, Apr. 14, 2016) (hereinafter Bender 1) in view of Sehl et al. (US 2010/0233246, Sep. 16, 2010) (hereinafter Sehl), Bender et al. (US 2015/0045507, Feb, 12, 2015) (hereinafter Bender 2), and further in view of Arthur et al. (US 20130337036, Dec. 19, 2013) (hereinafter Arthur).
The teachings of Bender 1, Sehl, and Bender 2 are discussed above. Bender 1, Sehl, and Bender 2 do not disclose wherein the fibers of the mesh have a mean diameter of 1-500 µm and wherein the mesh is a felt structure.
However, Arthur discloses a fibrous tissue sealant in the form of an anhydrous fibrous sheet comprising a first component which is a fibrous polymer containing electrophilic or nucleophilic groups and a second component capable of crosslinking the first component when the sheet is exposed to an aqueous medium. The fibrous tissue sealant may be useful as a general tissue adhesive for medical applications (abstract). The fibrous polymer sheet may have a fiber diameter of about 1-3 µm (¶ [0187]). The fibers may be laid down to give a fine felt (¶ [0220]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the fibers of the mesh to have a diameter of about 1-3 µm since Bender 1 does not disclose a fiber diameter for the mesh and this is a known and effective diameter for fibers forming a sheet for tissue adhesion as taught by Arthur.
Bender 1 discloses wherein a mesh is a sheet made of fibers. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have laid down the fibers to give a fine felt since this is another known and effective configuration to formulate a sheet for tissue adhesion as taught by Arthur.
Response to Arguments
Applicant argues that Arthur does not remedy the deficiencies of Bender 1, Sehl, and Bender 2.
The Examiner submits that arguments regarding Bender 1, Sehl, and Bender 2 have been discussed above and are unpersuasive. Therefore, the rejection is maintained.
3. Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Bender et al. (WO 2016/056901, Apr. 14, 2016) (hereinafter Bender 1) in view of Sehl et al. (US 2010/0233246, Sep. 16, 2010) (hereinafter Sehl), Bender et al. (US 2015/0045507, Feb, 12, 2015) (hereinafter Bender 2), and further in view of Nur et al. (US 2011/0045034, Feb. 24, 2011) (hereinafter Nur).
The teachings of Bender 1, Sehl, and Bender 2 are discussed above. Bender 1, Sehl, and Bender 2 do not disclose wherein the product is in a sealed package.
However, Nur discloses a sealed package containing a sterile ready to use cross-linked gelatin sponge, which enables removal of the patch without contamination (¶ [0116]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have the product in a sealed package in order to avoid contamination as taught by Nur.
Response to Arguments
Applicant argues that Nur does not remedy the disclosure deficiencies of Bender 1, Sehl, and Bender 2.
The Examiner submits that arguments regarding Bender 1, Sehl, and Bender 2 have been addressed above and are unpersuasive. Therefore, this rejection is maintained.
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 1-4, 7-13, and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16, 27 and 28 of copending Application No. 17/573,537 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims recite a more specific version of the instant claims (i.e., the conflicting claims recite wherein the particles additionally comprise a polysaccharide) and thus read on the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants respectfully defer these issues until the application is otherwise in condition for allowance. Since this has not occurred, the rejection is maintained.
Conclusion
Claims 1-4, 7-13, and 16-19 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TRACY LIU/Primary Examiner, Art Unit 1614