DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
INFORMATION DISCLOSURE STATEMENT
2. Information Disclosure Statements filed 6/23/2025 is acknowledged.
Claim Rejections - 35 USC § 103
3. 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 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 1 is rejected under 35 U.S.C. 103 as being unpatentable over Bellas et al. (US 2014/0308362) in view of Van Epps et al. (US Patent 9,334, 262), Serban et al. (US 2015/0057685), Fuentes et al. “The effect of hyaluronic acid on silk fibroin confirmation” and Pavlovic et al. (US 2014/0315828).
Bellas et al. (US 2014/0308362) (hereinafter Bellas et al.) disclose filler compositions and kits for augmenting tissue by injection (abstract). The injection device is a syringe which can comprise a needle, a cannula and/or catheter (i.e., delivery device) (para 0024 and claim 121). The injectable composition and/or the silk fibroin particles can further comprise at least one active agent which may be anesthetics such as lidocaine (paras 0084-0085 and 0088). In some embodiments the compositions and/or silk fibroin particles can further comprise at least additional material for soft tissue augmentation, e.g., dermal filler materials (para 0093) and examples of such materials include hyaluronic acid (paras 0039 and 0249). The injectable composition comprises silk fibroin particle with sizes of about 500 nm-5000 µm (para 0172). This is a range that overlaps with the instant claims. 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). The injectable composition requires silk fibroin particles (claim 115) and the particles have a porosity of at least about 1 % or at least about 5 % (claims 119-120). Bellas et al. disclose Hyaluronic acid (HA) is a glycosaminoglycan that is naturally found in the human body and is widely distributed throughout connective, epithelial, and neural tissues. Compositions of non-crosslinked hyaluronic acid tend to degrade within a few months after injection and thus require fairly frequent reinjection to maintain their soft tissue augmenting effect. More recently, compositions of cross-linked hyaluronic acid have been used for soft tissue augmentation. However, such cross-linked compositions contain fairly large particles, around approximately 2 mm each, of hyaluronic acid suspended in a gel. While the larger particles could have a longer lasting effect, the larger particle size can make the injection more challenging and create an unpleasant experience to a recipient (para 0006). In some embodiments the silk fibroin can be also mixed with other biocompatible and/or biodegradable polymers to form mixed polymer particles comprising silk fibroin where the one or more biocompatible and/or biodegradable polymers can be hyaluronic acid (para 0046). Bellas et al. disclose in an alternative approach, silk fibroin particles can be mixed with other polymers, for examples, hyaluronic acid, to prolong the release of certain growth factors or cytokines and to stabilize the functionality (para 0137). Thus, Bellas et al. clearly discloses silk fibroin particles with hyaluronic acid. Bellas et al. disclose the needle or cannula gauge can range from 12 to 34, 15 to 34, 20 to 32, or 25 to 30. The size of the needle or cannula can be determined to allow for an appropriate extrusion force of less than 40N (nominal deliverable force for a human hand) (para 0108). The silk fibroin particles have a porosity of at least about 70 % (paras 0165 and 0169). The pores have a size of about 1 µm to about 1000 µm (para 0171). The silk fibroin particles have a size of about 1 µm to 2000 µm (para 0173) and 10 µm to 1500 µm (para 0174). The silk fibroin matrix can be combined with glycerol that affects flexibility of the matrix (i.e., plasticizer) (bottom or para 0041 and para 0080-glycerol). Bellas et al. disclose that in some embodiments, the silk fibroin particles described herein can comprise porous structures, e.g., to mimic the structural morphology of a native tissue, to modulate the degradation rate/volume retention rate of the silk fibroin particles, and/or to module release profile of an active agent embedded therein, if any. As used herein, the terms "porous" and "porosity" are generally used to describe a structure having a connected network of pores or void spaces (which can, for example, be openings, interstitial spaces or other channels) throughout its volume (i.e., interconnected). The term "porosity" is a measure of void spaces in a material, and is a fraction of volume of voids over the total volume, as a percentage between 0 and 100% (or between 0 and 1) (para 0050). The composition is contained in the delivery device (claim 121). Based on the disclosure of Bellas et al. it appears that cross-linked hyaluronic acid is more preferable. Regarding the extrusion force standard deviation which is measured when extruding the composition through a 18-30 gauge needle, the Bellas et al. reference discloses compositions with overlapping extrusion forces measured with the same needle sizes and thus one would reasonably conclude that the standard deviation would also overlap. Bellas et al. disclose pre-loaded syringes (see paras 0024, 0145-1050, 0261-0263, 0297, 0299 and 0313).
Claims 7 essentially requires the interconnected pores have a diameter of 20 µm to about 100 µm. If all the interconnected pores have the recited diameters then it would necessarily follow that the average (50 %) would also have the diameter. Bellas et al. disclose connected (i.e., interconnected) pores (para 0050) and that the pore can be adapted to be any shape e.g., circular, elliptical or polygonal. The particles can be adapted to have pore size of about 10nm to 2000µm, about 50 nm-1500µm, about 0.5 um-1500 µm, from 1 µm to 1500 µm, 2 µm-1500µm, 1 µm-1000 µm, 3-1000 µm, 1-500 µm, or 3-500 µm (para 0052). In some embodiments the pore size can refer to the longest dimension of a pore, e.g., a dimeter (i.e., circular) of a pore having a circular cross section (para 0052). Bellas et al. disclose the pore size of the porous silk fibroin particles can range from about 10 nm to about 2000 µm, from about 50 nm to about 1500 µm, from about 0.5 µm to about 1500 µm, from about 1 µm to about 1000 µm, or from about 1 µm to about 500 µm (para 0016). The prior art discloses pore sizes from 1 µm to 500 µm and therefore the average pore size must necessarily be between 20 µm and 100 µm and would overlap with the instantly claimed range.
Based on the disclosure of Bellas et al. it appears that cross-linked hyaluronic acid is more preferable however, Van Epps et al. (US Patent 9,334, 262) (hereinafter Van Epps et al.) disclose hydrogels that contain crosslinked glycosaminoglycan polymer which can be hyaluronan (col. 32, lines 9-20). The hydrogel comprises crosslinked polymers of hyaluronan (col. 33). Van Epps et al. disclose aspects of the present specification provide, in part, a hydrogel material comprising a crosslinked glycosaminoglycan polymer having a degree of crosslinking. Van Epps et al. disclose as used herein, the term “degree of crosslinking” refers to the percentage of glycosaminoglycan polymer monomeric units, such as, e.g., the disaccharide monomer units of hyaluronan that are bound to a cross-linking agent. The degree of crosslinking is expressed as the percent weight ratio of the crosslinking agent to glycosaminoglycan monomeric unit within the crosslinked portion of the hydrogel material. It is measured by the weight ratio of glycosaminoglycan monomers to crosslinker. Thus, a hydrogel material that has a crosslinked glycosaminoglycan polymer with a 4% degree of crosslinking means that on average there are four crosslinking molecules for every 100 glycosaminoglycan monomeric units. Every other parameter being equal, the greater the degree of crosslinking, the harder the hydrogel becomes. Non-limiting examples of a degree of crosslinking useful to make the hydrogel materials disclosed herein include about 1% to about 15% (col. 32, lines 15-35). Thus, the degree of crosslinking (crosslink density) is recognized as a result effective variable where the result is the hardness of the hydrogel. The hydrogel can comprise uncrosslinked glycosaminoglycan polymers which may be hyaluronan polymer. Uncrosslinked glycosaminoglycan polymers are water soluble and generally remain fluid in nature. As such, uncross-linked glycosaminoglycan polymers are often mixed with a glycosaminoglycan polymer-based hydrogel material as a lubricant to facilitate the extrusion process of the hydrogel material through a fine needle (col. 34, lines 65-col. 35, line 3). The hydrogel can comprise uncrosslinked hyaluronan with mean molecular weights of 100,000 Da to about 200,000 Da (i.e. 200 Kda) (col. 35, lines 40-63). The hydrogels contain crosslinked and uncrosslinked glycosaminoglycan polymers (i.e., hyaluronan (col. 37, lines 33-44). The crosslinked glycosaminoglycan represents about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 % , about 7 %, about 8 %, about 9 %, about 10 % present of the hydrogel material (col. 32, lines 9-41). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have the hyaluronic acid crosslinked and further have the hydrogel comprise uncrosslinked hyaluronic acid. One would have been motivated to do so to fine tune the degradation profile of the hydrogel and further provide a lubricant to facilitate the extrusion process of the hydrogel material.
The modified Bellas does not disclose the hyaluronic acid and the porous silk fibroin particles have a volume ratio of about 5:95 to 95:5, about 80:20 to about 40:60, or about 70:30 to about 30:70
Serban et al. (US 2015/0057685) (hereinafter Serban et al.) disclose a composition containing cross-linked silk fibrin and hyaluronic acid and the weight ratio can be from 1:1,2:1 or 3:1 (para 0089-cited for crosslinked HA and Table 2 which is described by paragraphs 0164-0169). Serban discloses that the 3:1 volume ratio yielded the best biological outcome (equivalent to the lowest cell concentration) and that decreasing the HA amount in the formulation can increase cell adhesion (para 0184).
Fuentes et al. “The effect of hyaluronic acid on silk fibroin confirmation” disclose that hyaluronic acid has an effect in enhancing (3-sheet content observed for silk fibroin and enhancement of (3-sheet content observed for the silk fibroin/hyaluronic acid matrices correlated with improved mechanical properties: blended matrices had higher compressive moduli and higher breaking strengths than pure silk fibroin matrices (abstract). The ratio used was a 1.5 % w/v (SF to HA ratio w/w/ 60:40) (section 2.3 and table 1).
Pavlovic et al. (US 2014/0315828) (hereinafter Pavlovic et al.) disclose silk fibroin hydrogel component or particle and matrix polymer hydrogel component or particle (para 0063). The matrix polymer may be hyaluronan (para 0055) (i.e., hyaluronic acid) these matrix polymers may be crosslinked (para 0057) and the paragraph gives examples of hyaluronan crosslinking agents. The silk fibroin hydrogel or particle and matrix polymer hydrogel component or particle may be in a ratio of .1% (v/v) silk fibroin hydrogel and about 99.9% (v/v) matrix polymer hydrogel, about 1% (v/v) silk fibroin hydrogel and about 99% (v/v) matrix polymer hydrogel, about 5% (v/v) silk fibroin hydrogel and about 95% (v/v) matrix polymer hydrogel, about 10% (v/v) silk fibroin hydrogel and about 90% (v/v) matrix polymer hydrogel, about 15% (v/v) silk fibroin hydrogel and about 85% (v/v) matrix polymer hydrogel, about 20% (v/v) silk fibroin hydrogel and about 80% (v/v) matrix polymer hydrogel, or about 25% (v/v) silk fibroin hydrogel and about 75% (v/v) matrix polymer hydrogel (para 0063). The mixing set-up used for mixing hyaluronic acid and silk fibroin influences the dispersion of silk fibroin inside the hyaluronic acid bulk. Fast mixing creating a turbulent flow, such as syringe-to-syringe passing, favors the aggregation of silk fibroin molecules and the formation of larger particles (10-70 uM) inside the gel. Using a slow laminar flow, typically in a static mixer, a uniform dispersion of silk fibroin with fewer particles (1-10 uM) is obtained (para 0011).Pavlovic disclose to increase in vivo residence time, the liner chains of hyaluronic acid can be crosslinked (para 0008). Fast mixing creating a turbulent flow, such as syringe-to-syringe passing, favors the aggregation of silk fibroin molecules and the formation of larger particles (10-70 uM) inside the gel. Furthermore, crosslinking hyaluronic acid can be used to increase in vivo residence time which would be motivation to further have the hyaluronic acid crosslinked in Bellas.
Absent any evidence of criticality, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to optimize the volume ratio of silk fibroin/HA. One would have been motivated to optimize the HA amount present to tailor to the cell adhesive properties of the composition and to tailor toward the desired mechanical properties such as compressive moduli and breaking strengths.
DOUBLE PATENTING
4. 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over US Patent 11617815. Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to silk fibroin and crosslinked hyaluronic acid compositions containing properties, such as volume ratio, average pore size, and average porosity, crosslink density that overlap. The differences being that claim 1 recites device whereas claim 1 of the instant application is a injectable composition however, claim 1 of the patent makes clear the “article” is an injection delivery device containing the composition.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of US Patent 11642440. Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to silk fibroin and crosslinked hyaluronic acid compositions containing properties, such as volume ratio, average pore size, and average porosity, crosslink density that overlap. The differences being that claim 1 of instant claims recites crosslink density of greater than or equal to 4 mol % about 30 mol % and recites ratio of the crosslinked hyaluronic acid to biocompatible particles (e.g., silk fibroin particles) of about 5:95 to about 95:5 wherein claim 1 of the patent recites volume ratio of hyaluronic acid to silk fibroin particles is greater than or equal to 50:50 and less than or equal to 75:25 and the crosslinked density of the hyaluronic acid is greater than or equal to 8 % and less than or equal to 20 mol %. These are overlapping amounts. 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).
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of US Patent 11623019. Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to silk fibroin and crosslinked hyaluronic acid compositions containing properties, such as volume ratio, average pore size, and average porosity, crosslink density that overlap. The differences being that claim 1 recites injectable composition whereas claim 1 of the patent recites a kit however, claim 1 of the patent makes clear the kit is an injection delivery device containing the composition. Additionally the volume ratio of the crosslinked hyaluronic acid to the particles is greater than or equal to 50:50 and less than or equal to 95:5 which are amounts that overlap. 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)
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of US Patent 12214106. Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to silk fibroin and crosslinked hyaluronic acid compositions containing properties, such as volume ratio, average pore size, and average porosity, crosslink density that overlap. The differences being that claim 1 of the patent recites the silk fibroin particles are hydrated and have a hydrated density of about 0.4 g/mL particles to about 1 g/mL particles. The structure of the claims overlap in scope.
CORRESPONDENCE
5. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danah Al-awadi whose telephone number is (571) 270-7668. The examiner can normally be reached on 9:00 am - 6:00 pm; M-F (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Danah Al-Awadi/
Primary Examiner, Art Unit 1615
Prosecution Insights