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 .
Claim Status
Claims 1-23 were previously pending.
By virtue of the 30 January 2025 Preliminary Amendment, Applicant: amended claims 3-4, 6-7, 9-10, 14-16, 18, and 20-23; cancelled claims 5, 8, and 19; and did not add new claims.
Therefore, claims 1-4, 6-7, 9-18, and 20-23 are now pending and currently under examination.
Priority
Examiner acknowledges Applicant’s claim to the following priority:
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Information Disclosure Statement (IDS)
The IDS (1) filed on 30 January 2025 has been considered by the examiner. A signed copy is enclosed.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 4, 7, 10, 12-13, 16, 18, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instances, claims 2, 4, 7, 10, 12-13, 16, 18, and 21 recite a broad limitation, and the claim also recites several narrower limitations. In addition, some of the rejected claims recite the narrower limitation as a ‘preferable’ limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites, “[t]he implantable tissue scaffold of claim 4)…” However, ‘4b)’ is not a previously set forth claim but rather refers to alternative limitation (b) appearing within claim 4. A dependent claim must refer to a previously set forth claim and further limit the subject matter thereof. Accordingly, claim 6 does not comply with 35 USC 112(d).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 2, 9, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Li (“In vitro degradation of porous nano-hydroxyapatite/collagen/PLLA scaffold reinforced by chitin fibers,” published 09 November 2005) in further view of Nasrin (“Preparation of Chitin-PLA laminated composite for implantable application,” published: 02 October 2017).
Regarding claim 1 –
Li teaches a novel porous scaffold for bone tissue engineering prepared with nano-hydroxyapatite/collagen/poly-L-lactic acid (PLLA) composite reinforced by chitin fibers (abstract). Li teaches chitin induces fibroblasts to release interleukin-8, which is involved in the migration and proliferation of fibroblasts and vascular endothelial cells, making scaffolds composed of PLLA and chitin create an appropriate environment for the regeneration of tissue (pp. 716-717). The scaffold, Li teaches, is comprised of chitin fibers, PLLA, and dicyclohexylcarbodimide (DCC) at a molarity (M) ratio of 1:4:2 (p. 717).
Thus, while Li teaches an implantable tissue scaffold comprising a biocompatible organic polymer and embedded chitin, Li does not clearly disclose the final concentration of chitin in the completed scaffold as a percentage by weight of the entire scaffold. However, this limitation is made obvious in further view of Nasrin.
Nasrin teaches a method to fabricate laminated chitin-polylactic acid (PLA) bio absorbable composite to use in artificial bone implant (p. 200). Nasrin teaches that chitin-reinforced PLA compositions were developed specifically for implantable applications, including bone and dental implants, and reports good dispersion of chitin into PLA and strong interfacial actions between the polymer and chitin (abstract). This improvement of mechanical properties and the results of antimicrobial and cytotoxicity of the composites, Nasrin explains, make the composites a suitable candidate for implant application in the biomedical sector (abstract). Nasrin prepares compositions containing 0.04, 0.20, 0.40, 0.60, and 0.80 g chitin with 4.00 g PLA, which corresponds to approximately 0.99, 4.76, 9.09, 13.04, and 16.67 wt% chitin, respectively, when calculated relative to total PLA plus chitin solids (p. 201, Table 1). Each of the disclosed wt% chitin fall within the instantly claimed range of claim 1.
Regarding claim 2 –
Li expressly the chitin is 60% deacetylated (p. 717), which falls within the instantly claimed range of claim 2.
Regarding claim 9 –
Both Li and Nasrin expressly employ the biodegradable polymer PLA or a species thereof.
Regarding claim 23 –
Both Li and Nasrin expressly teach use of the composite on bone. Li further expressly states the reinforced composite may serve as a scaffold for bone tissue engineering. Thus, use of the scaffold in treating a bone defect would have been directly suggested by Li.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to employ in Li’s PLLA/chitin tissue scaffold a chitin loading within the range taught by Nasrin because both references concern implantable PLA/chitin biomaterials, both use chitin as a reinforcing biocompatible component of a lactic acid polymer matrix, and Nasrin further demonstrates that such chitin loadings can be successfully incorporated into PLA while providing useful physical and biomedical properties. The skilled artisan would have had a reasonable expectation of success in doing so because both references successfully prepare PLA/chitin composite biomaterials with improved physical and mechanical properties.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Li and Nasrin as applied to claims 1, 2, 9, and 23 above, and further in view of Sashiwa (“N-Acetyl group distribution in partially deacetylated chitins prepared under homogeneous conditions,” published: 1993).
Li and Nasrin are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claim 3, this is made obvious over Sashiwa.
Regarding claim 3 –
Sashiwa investigates partially deacetylated chitin and determines that partially deacetylated chitins prepared under homogeneous conditions exhibited a random distribution of acetylated/deacetylated units (abstract, p. 168).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to select the known randomly deacetylated chitin distribution for Li’s scaffold because Li already employs partially deacetylated chitin and the art recognized that the distribution of glucosamine/N-acetylglucosamine units is a structural characteristic controlled by the deacetylation process. As taught by Sashiwa, randomly deacetylated chitin was a known form of partially deacetylated chitin and would have been expected to retain the recognized biomedical utility of chitin while providing known differences in solubility and material behavior.
Claims 4, 6, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Li and Nasrin as applied to claims 1, 2, 9, and 23 above, and further in view of Sanei (JP 2990248B2, published: 13 December 1999) and Gislason (US Pat. No. 9,078,949 B2, date of patent: 14 July 2015).
Li and Nasrin are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claims 4, 6, and 7, this is made obvious over Sanei and Gislason.
Regarding claim 4, limitation (a) –
Sanei teaches amorphous, water-soluble, partially deacetylated chitin having a degree of deacetylation (DD) of about 35 to 65% (p. 1).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the amorphous form of Sanei in Li’s scaffold because amorphous partially deacetylated chitin was a known form of the same material and provided enhanced hydration/solubility relative to more crystalline chitin. One would be motivated to do so because Sanei teaches that partially deacetylated chitin within substantially the same DD range may be provided in amorphous form.
Regarding claim 4, limitation (b) –
Gislason teaches methods to use degree of deacetylation of a partially deacetylated chitin polymer in order to modulate physical and biological parameters in a calcium phosphate composite for bone implant applications. Gislason further teaches highly soluble partially deacetylated chitin having enhanced hydration behavior and expressly describes preparation of a 43% DD material that is readily dispersed in water and dissolved upon addition of acid (col. 13, lines 15-50).
The precise water uptake of partially deacetylated chitin is dependent upon known material variables including DD, crystallinity, molecular weight, and particle morphology. Where increased swelling and hydration were desired for a tissue scaffold, optimization of these known variables to obtain a desired absorption threshold would have involved nothing more than routine experimentation.
Regarding claim 6 –
Gislason teaches dispersing a 43% DD partially deacetylated chitin in water and thereafter adding citric acid to dissolve the polymer (Example 1.3.1, col. 13, lines 15-22). Example 1.3.2 likewise teaches dissolution of the partially deacetylated chitin in 1% citric acid solution (col. 13, lines 23-50). Gislason further provides an example whereby chitosan was exposed to water and subsequently forms a chitosan gel (col. 13, lines 55-67).
Regarding claim 7 –
Gislason teaches partially deacetylated chitin having a molecular weight greater than about 10 kDa (col. 4, lines 27-36), which overlaps the broadly claimed 200 Da to 2000 kDa range. Gislason further expressly teaches spray dried partially deacetylated chitin having an average particle size of about 5 µm with a distribution of approximately 3-10 µm (col. 13, lines 34-37), which falls within the claimed ranges.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to employ Gislason’s partially deacetylated chitin particles in the Li scaffold because particle size and molecular weight were recognized material parameters affecting dispersion, processing, degradation, and biological behavior. One of ordinary skill would have expected such particles to be compatible with Li’s biodegradable polymer scaffold.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Li and Nasrin as applied to claims 1, 2, 9, and 23 above, and further in view of Custodio (“Powder Loading Effects on the Physiochemical and Mechanical Properties of 3D Printed Poly Lactic Acid/Hydroxyapatite Biocomposites,” published: 28 January 2021).
Li and Nasrin are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claim 10, this is made obvious over Custodio.
Regarding claim 10 –
Custodio teaches incorporating hydroxyapatite (HAp) with PLA matrix in 3D printed PLA/Hap composite material (abstract). Custodio further teaches composites containing 5, 10, and 15 wt% HAp (p. 114, Table 1), all falling within the claimed range.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to select a hydroxyapatite loading parameter within the range taught by Custodio in Li’s hydroxyapatite-containing scaffold because hydroxyapatite was already present in Li for its recognized bone-related function and Custodio demonstrates successful PLA/HAp composites in 3D printed constructs.
To the extent the claimed calcium phosphate microparticle diameter is not taught by Li or Custodio, the particle diameter would have been recognized as a result-effective variable affecting dispersion, printability, surface area, dissolution, and mechanical behavior. Routine selection of a micron scale calcium phosphate powder suitable for uniform dispersion in the polymer matric would have been within the skilled artisan’s capabilities.
Claims 11, 12, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Li in further view Nasrin and Rajabi (“Chitosan hydrogels in 3D printing for biomedical applications,” published 10 February 2021).
Li and Nasrin are discussed above as the combination makes obvious an implantable tissue scaffold comprising 0.99 to 16.67 wt% chitin and 83.3 to 99.0 wt% PLA. While neither Li nor Nasrin categorize characterize the chitin/PLA composite ‘for 3D printing’ or any of the limitations of claims 11, 12, 20, and 21, this limitation is made obvious over Rajabi.
Regarding claim 11 –
Rajabi teaches 3D printing as a biofabrication technique for producing patient-specific tissue engineering scaffolds and expressly discusses chitosan-based materials as 3D printing inks and as components/coatings of 3D printed biomedical scaffolds (abstract, p. 5). Rajabi further identifies tissue regeneration and next-generation biomedical implants as uses for such 3D-printed chitosan containing materials (abstract, p. 18).
Regarding claim 12 –
Li expressly employs 60% deacetylated chitin in its PLLA/chitin bone scaffold.
Regarding claim 20 –
Nasrin expressly employs PLA and Li expressly employs PLLA in the chitin bone scaffold.
Regarding claim 22 –
Rajabi expressly teaches 3D printing of chitosan-containing materials to form tissue engineering scaffolds and biomedical implants and identifies 3D printing as useful for producing patient-specific scaffolds having complex geometries for tissue regeneration.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to adapt the implantable PLA/chitin composition of Li and Nasrin for the 3D printing technique of Rajabi because PLA was a known thermoplastic additive manufacturing polymer and Rajabi expressly teaches the desirability of using chitin-derived/chitosan-containing materials in 3D printed biomedical scaffolds. A skilled artisan would have been motivated to do so to obtain the recognized benefits of additive manufacturing, including controlled scaffold geometry, patient-specific form, and tissue regenerative architecture. One of ordinary skill would have had a reasonable expectation of success because Rajabi had already demonstrated both processable PLA composites and 3D printable chitin-derived biomaterial systems.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Li, Nasrin, and Rajabi as applied to claims 11, 12, 20, and 22 above, and further in view of Wang (“Intra-articular injection of N-acetylglucosamine and hyaluronic acid combined with PLGA scaffolds for osteochondral repair in rabbits,” published 31 December 2018).
Li, Nasrin, and Rajabi are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claim 13, this is made obvious over Wang.
Regarding claim 13 –
Wang teaches use of N-acetylglucosamine (GlcNAc/NAG) in conjunction with biodegradable PLGA scaffolds for osteochondral repair (abstract). Wang reports that combining PLGA implantation with GlcNAc administration promotes cartilage and bone regeneration and osteochondral repair (abstract).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to include GlcNAc as a bioactive component associated with the biodegradable polymer scaffold of Li/Nasrin/Rajabi because Wang establishes the known therapeutic compatibility and regenerative benefit of GlcNAc with a biodegradable polymer scaffold to assist in bone repair.
The precise amount of GlcNAc represents a result-effective variable because the amount would be selected to provide sufficient biological activity while maintaining the processibility and scaffold mechanical properties. In view of the breadth of the claimed range, routine optimization of the amount of GlcNAc incorporated or retained in the scaffold would have been within ordinary skill absent evidence of criticality or unexpected results associated with the claimed range.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Li, Nasrin, and Rajabi as applied to claims 11, 12, 20, and 22 above, and further in view of Sashiwa.
Li, Nasrin, and Rajabi are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claim 14, this is made obvious over Sashiwa.
Regarding claim 14 –
Sashiwa investigates partially deacetylated chitin and determines that partially deacetylated chitins prepared under homogeneous conditions exhibited a random distribution of acetylated/deacetylated units (abstract, p. 168).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to select the known randomly deacetylated chitin distribution for Li’s scaffold because Li already employs partially deacetylated chitin and the art recognized that the distribution of glucosamine/N-acetylglucosamine units is a structural characteristic controlled by the deacetylation process. As taught by Sashiwa, randomly deacetylated chitin was a known form of partially deacetylated chitin and would have been expected to retain the recognized biomedical utility of chitin while providing known differences in solubility and material behavior.
Claims 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Nasrin, and Rajabi as applied to claims 11, 12, 20, and 22 above, and further in view of Sanei and Gislason.
Li, Nasrin, and Rajabi are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claims 15-18, this is made obvious over Sanei and Gislason.
Regarding claim 15 –
Sanei teaches amorphous, water-soluble, partially deacetylated chitin having a degree of deacetylation (DD) of about 35 to 65% (p. 1).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the amorphous form of Sanei in Li’s scaffold because amorphous partially deacetylated chitin was a known form of the same material and provided enhanced hydration/solubility relative to more crystalline chitin. One would be motivated to do so because Sanei teaches that partially deacetylated chitin within substantially the same DD range may be provided in amorphous form.
Regarding claim 16 –
Gislason teaches methods to use degree of deacetylation of a partially deacetylated chitin polymer in order to modulate physical and biological parameters in a calcium phosphate composite for bone implant applications. Gislason further teaches highly soluble partially deacetylated chitin having enhanced hydration behavior and expressly describes preparation of a 43% DD material that is readily dispersed in water and dissolved upon addition of acid (col. 13, lines 15-50).
The precise water uptake of partially deacetylated chitin is dependent upon known material variables including DD, crystallinity, molecular weight, and particle morphology. Where increased swelling and hydration were desired for a tissue scaffold, optimization of these known variables to obtain a desired absorption threshold would have involved nothing more than routine experimentation.
Regarding claim 17 –
Gislason teaches dispersing a 43% DD partially deacetylated chitin in water and thereafter adding citric acid to dissolve the polymer (Example 1.3.1, col. 13, lines 15-22). Example 1.3.2 likewise teaches dissolution of the partially deacetylated chitin in 1% citric acid solution (col. 13, lines 23-50). Gislason further provides an example whereby chitosan was exposed to water and subsequently forms a chitosan gel (col. 13, lines 55-67).
Regarding claim 18 –
Gislason teaches partially deacetylated chitin having a molecular weight greater than about 10 kDa (col. 4, lines 27-36), which overlaps the broadly claimed 200 Da to 2000 kDa range. Gislason further expressly teaches spray dried partially deacetylated chitin having an average particle size of about 5 µm with a distribution of approximately 3-10 µm (col. 13, lines 34-37), which falls within the claimed ranges.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to employ Gislason’s partially deacetylated chitin particles in the Li scaffold because particle size and molecular weight were recognized material parameters affecting dispersion, processing, degradation, and biological behavior. One of ordinary skill would have expected such particles to be compatible with Li’s biodegradable polymer scaffold.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Li, Nasrin, and Rajabi as applied to claims 1, 2, 9, and 23 above, and further in view of Custodio.
Li, Nasrin, and Rajabi are discussed above as the combination makes obvious an implantable tissue scaffold comprising chitin and PLA. While neither reference expressly discloses the limitations of claim 21, this is made obvious over Sanei and Gislason.
Regarding claim 21 –
Custodio teaches incorporating hydroxyapatite (HAp) with PLA matrix in 3D printed PLA/Hap composite material (abstract). Custodio further teaches composites containing 5, 10, and 15 wt% HAp (p. 114, Table 1), all falling within the claimed range.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to select a hydroxyapatite loading parameter within the range taught by Custodio in Li’s hydroxyapatite-containing scaffold because hydroxyapatite was already present in Li for its recognized bone-related function and Custodio demonstrates successful PLA/HAp composites in 3D printed constructs.
To the extent the claimed calcium phosphate microparticle diameter is not taught by Li or Custodio, the particle diameter would have been recognized as a result-effective variable affecting dispersion, printability, surface area, dissolution, and mechanical behavior. Routine selection of a micron scale calcium phosphate powder suitable for uniform dispersion in the polymer matric would have been within the skilled artisan’s capabilities.
Conclusion
Claims 1-4, 6, 7, 9-18, and 20-23 are rejected. No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A. Rossi whose telephone number is (571)272-0138. The examiner can normally be reached M-Th 7:30-5:30 (MST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at (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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/JULIA A. ROSSI/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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