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 .
Election/Restrictions
Applicant’s election of Group I (claims 1-7 and 28-30) in the reply filed on November 10, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 8-27 and 31-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected groups, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on November 10, 2025.
The election/restriction is made FINAL.
Summary
Claims 1-7 and 28-30 are pending in this office action. Claims 8-27 and 31-33 have been withdrawn from consideration. Applicant is encouraged to amend the withdrawn claims for their correct alignment with the pending claims. All pending claims are under examination in this application.
Priority
The current application filed on May 18, 2023 is a 371 of PCT/US2021/059949 filed November 18, 2021. The current application claims to provisional patent application 63/115,199 filed on November 18, 2020.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on November 10, 2025 and May 18, 2023 are acknowledged. A signed copy of both documents is attached to this office action.
Claim Objections
Claims 1-7 and 28-30 are objected to because of the following informalities:
Claim 1 has the phrase “…optionally wherein….”. The way the claim is written, it is unclear whether everything after this phrase is optional. Please clarify this for the skilled artisan. [For the purposes of rejecting the claim under 35 U.S.C. 103, the Examiner has interpreted the second “and” phrase as a limitation that is not optional.]
Dependent claims 1-3, 6-7, and 28-30 fail to cure the defect of claim 1.
In a similar manner, claim 2 has the “….optionally wherein…” clause within the middle of the claim, and is interpreted in the same manner as claim 1. Clarification is required.
Dependent claims 4 and 5 fail to cure the defect of claim 2.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 28 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 28 references “diameter 29,” which the Examiner assumes is a Figure. This makes the claim unclear and indefinite. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim. See MPEP § 608.01(m) for information pertaining to the treatment of reference characters in a claim [see MPEP § 2173.05(s)].
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 non-obviousness.
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 1-7 and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Harley et al. (US2014/0309738A1) in view of Yow et al. (Polymers, 2011), Alegret et al. (Biomacromolecules, 2019), Weisgerber et al. (Journal of the Mechanical Behavior of Biomedical Materials, 2013) and Wei (WO2017/196595A1).
[The Examiner is going to introduce each reference and then combine them where appropriate to reject the instant claims.]
1. Harley et al.
Harley et al. is regarded as being the prior art closest to the subject-matter of the present application as it teaches membrane-scaffold composites for tissue engineering applications (see title). Additionally, Harley et al. disclose collagen-glycosaminoglycan membrane shell scaffold core composites for connective tissue engineering that avoids aspects of the typical tradeoff between mechanical properties (i.e. modulus, failure strength) and bioactivity (i.e., permeability and porosity) for porous tissue engineering scaffolds. The relative density of the collagen glycosaminoglycan scaffold core can be about 0.5 to about 0.95 while the membrane shell can be about 0.001 to 25 about 0.2. The core-shell composite can be tubular and the composite can have a diameter of about 1 mm to about 20 mm. The collagen glycosaminoglycan membrane shell can be perforated with about 25 to about 1000 micrometers openings or alternatively can be embossed with any range of pattern features from about 25 to about 1000 micrometers in size. The porous collagen glycosaminoglycan scaffold core can be populated with cells such as adult or embryonic stem cells, tenocytes, osteoblasts, nerve cells, cardiac cells, myocytes, fibroblasts or combinations thereof (see abstract).
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2. Yow et al.
Yow et al. teach a 3D electroactive polypyrrole-collagen fibrous scaffold for tissue engineering (see title). Additionally, Yow et al. disclose that fibers can provide topographical, biochemical and electrical cues that would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal or muscular cells. Here we report on the fabrication of polypyrrole-incorporated collagen-based fibers via interfacial polyelectrolyte complexation (IPC). The mean ultimate tensile strength of the fibers is 304.0 ± 61.0 MPa and the Young’s Modulus is 10.4 ± 4.3 GPa. Human bone marrow-derived mesenchymal stem cells (hMSCs) are cultured on the fibers in a proliferating medium and stimulated with an external electrical pulse generator for 5 and 10 days. The effects of polypyrrole in the fiber system can be observed, with hMSCs adopting a neuronal-like morphology at day 10, and through the upregulation of neural markers, such as noggin, MAP2, neurofilament, β tubulin III and nestin. This study demonstrates the potential of this fiber system as an attractive 3D scaffold for tissue engineering, where collagen is present on the fiber surface for cellular adhesion, and polypyrrole is encapsulated within the fiber for enhanced electrical communication in cell-substrate and cell-cell interactions. (see abstract).
3. Alegret et al.
Alegret et al. teach 3D scaffolds based on conductive polymers for biomedical applications (see title). Additionally, Alegret et al. disclose 3D scaffolds appear to be a cost-effective ultimate answer for biomedical applications, facilitating rapid results while providing an environment similar to in vivo tissue. These biomaterials offer large surface areas for cell or biomaterial attachment, proliferation, biosensing and drug delivery applications. Among 3D scaffolds, the ones based on conjugated polymers (CPs) and natural nonconductive polymers arranged in a 3D architecture provide tridimensionality to cellular culture along with a high surface area for cell adherence and proliferation as well electrical conductivity for stimulation or sensing. However, the scaffolds must also obey other characteristics: homogeneous porosity, with pore sizes large enough to allow cell penetration and nutrient flow; elasticity and wettability similar to the tissue of implantation; and a suitable composition to enhance cell−matrix interactions. In this Review, we summarize the fabrication methods, characterization techniques and main applications of conductive 3D scaffolds based on conductive polymers. The main barrier in the development of these platforms has been the fabrication and subsequent maintenance of the third dimension due to challenges in the manipulation of conductive polymers. In the last decades, different approaches to overcome these barriers have been developed for the production of conductive 3D scaffolds, demonstrating a huge potential for biomedical purposes. Finally, we present an overview of the emerging strategies developed to manufacture 3D conductive scaffolds, the techniques used to fully characterize them, and the biomedical fields where they have been applied (see abstract).
4. Weisgerber et al.
Weisgerber et al. teach the impact of discrete compartments of a multi-compartment collagen–GAG scaffold on overall construct biophysical properties (see title). In addition, Weisgerber et al. disclose that orthopedic interfaces such as the tendon-bone junction (TBJ) present unique challenges for biomaterials development. Here we describe a multi-compartment collagen–GAG scaffold fabricated via lyophilization that contains discrete mineralized (CGCaP) and non-mineralized (CG) regions joined by a continuous interface. Modifying CGCaP preparation approaches, we demonstrated scaffold variants of increasing mineral content (40 vs. 80 wt% CaP). We report the impact of fabrication parameters on microstructure, composition, elastic modulus, and permeability of the entire multi-compartment scaffold as well as discrete mineralized and non-mineralized compartments. Notably, individual mineralized and non-mineralized compartments differentially impacted the global properties of the multi-compartment composite. Of particular interest for the development of mechanically-loaded multi-compartment composites, the elastic modulus and permeability of the entire construct were governed primarily by the non-mineralized and mineralized compartments, respectively. Based on these results we hypothesize spatial variations in scaffold structural, compositional, and mechanical properties may be an important design parameter in orthopedic interface repair (see abstract).
5. Wei
Wei teaches osteoinductive fibrous bone chips (see title). Furthermore, Wei discloses an osteoinductive composition is provided which includes a plurality of surface demineralized fibrous bone chips. Each fibrous bone chip has a BET surface area from about 10 m2/gm to about 70 m2/gm. The osteoinductive composition can also include fully demineralized bone fibers. The osteoinductive composition including the surface demineralized fibrous bone chips with or without fully demineralized bone fibers can be placed in a covering, such as a mesh bag. The osteoinductive composition can include other bone structures and/or bioactive agents and/or ceramics. A method of treating a bone cavity in a patient in need thereof with the osteoinductive composition including a plurality of surface demineralized fibrous bone chips with or without fully demineralized bone fibers is also provided (see abstract).
Combination of Harley et al., Yow et al., and Alegret et al.
Regarding instant claim 1, Harley et al., Yow et al., and Alegret et al. teach a multicompartment conductive collagen scaffold composite, comprising a scaffold comprising collagen and an electrically conductive material. The necessary citations within Harley et al., Yow et al., and Alegret et al. that correspond to instant claim 1 are compiled within Table I.
Table I
Instant Claim 1
Harley et al., Yow et al., and Alegret et al. Citations
A multicompartment conductive collagen scaffold composite, comprising a scaffold comprising collagen and an electrically conductive material, optionally wherein the electrically conductive material comprises electrically conductive particles,
Harley et al. disclose a multicompartment collagen scaffold composite (see paragraph [0005] within Harley et al.), comprising a scaffold comprising collagen (see paragraph [0005] within Harley et al.).
Harley et al. fails to explicitly disclose conductive collagen scaffold; an electrically conductive material, optionally wherein the electrically conductive material comprises electrically conductive particles.
However, Yow et al. does disclose this limitation. Yow et al. is in the art of a collagen scaffold for tissue engineering (see title and abstract within Yow et al.). Yow et al. disclose development of an interfacial polyelectrolyte complexation (IPC)-based strategy that incorporates FeCl3-doped polypyrrole into a collagen-based polyelectrolyte complexation (PEC) fiber for the creation of a 3D electroactive biofunctional fibrous scaffold (see page 529, paragraph 5 within Yow et al.). Additionally, Yow et al. disclose that atomic force microscopy (AFM) confirmed the successful encapsulation of polypyrrole particles within the PEC fibers (see page 529, paragraph 5 and page 530, paragraph 1 within Yow et al.). Figure 2b within Yow et al. confirms the approximate size of these particles at approximately 1.4-3.0 mm (also see page 532, paragraph 1 within Yow et al.).
Alegret et al. supports both the Harley et al. and Yow et al. disclosures in their review (see page 74, 2. Fabrication methods of 3D scaffolds based on conductive polymers and page 80, Table 1 within Alegret et al.).
and further comprising longitudinally aligned pores.
Harley et al. disclose that the multicompartment collagen scaffold further comprises longitudinally aligned pores (see paragraph [0029] within Harley et al.).
Therefore, a research and development scientist (POSITA; person having ordinary skill in the art) could easily combine the teachings of Harley et al., Yow et al., and Alegret et al. to afford a multicompartment conductive collagen scaffold composite, comprising a scaffold comprising collagen and an electrically conductive material.
[Henceforth within the Office Action, all elements of instant claim 1 are taught by the combination of Harley et al., Yow et al., and Alegret et al.].
Regarding instant claim 3, Harley et al., Yow et al., and Alegret et al. teach wherein the scaffold comprising collagen, the first collagen scaffold and/or the second collagen scaffold comprises collagen-glycosaminoglycan (CG). Harley et al. disclose the scaffold comprising collagen, the first collagen scaffold and/or the second collagen scaffold comprises collagen-glycosaminoglycan (CG) (see paragraph [0005] within Harley et al.).
Regarding instant claims 6 and 7, Harley et al., Yow et al., and Alegret et al. teach wherein the electrically conductive particles are microparticles. Yow et al. disclose developed an IPC-based strategy that incorporates FeCl3-doped polypyrrole into a collagen-based PEC fiber for the creation of a 3D electroactive biofunctional fibrous scaffold (see page 529, paragraph 5 within Yow et al.). Additionally, Yow et al. disclose that AFM confirmed the successful encapsulation of polypyrrole particles within the PEC fibers (see page 529, paragraph 5 and page 530, paragraph 1 within Yow et al.). Figure 2b within Yow et al. confirms the approximate size of these particles at approximately 1.4-3.0 mm (also see page 532, paragraph 1 within Yow et al.). Furthermore, Yow et al. disclose that in the presence of an electrical stimulation, these conductive polymers can modulate cell adhesion, migration, protein secretion and DNA synthesis of electrically responsive cells, such as nerve, bone, muscle and cardiac cells (see page 529, paragraph 1 within Yow et al.).
Regarding instant claim 28, Harley et al., Yow et al., and Alegret et al. teach wherein pore size ranges from about 50 mm to about 250 mm. Harley et al. disclose that the transverse pore size can be about 500 to about 20 μm, or any range or value between about 500 to about 20 μm (see paragraph [0030] within Harley et al.; see also PTO-892 NPL W).
Regarding instant claim 29, Harley et al., Yow et al., and Alegret et al. teach wherein the pores are elongated. Harley et al. disclose that an anisotropic scaffold, for example a cylindrical scaffold, has a significantly greater pore aspect ratio in the longitudinal than in the transverse planes meaning that the pores are elongated in the direction of the scaffold longitudinal axis (see paragraph [0029] within Harley et al.).
Combination of Harley et al., Yow et al., Alegret et al., Weisgerber et al., and Wei
Regarding instant claim 2, Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei teach further comprising a first compartment comprising a first collagen scaffold and an electrically conductive material, optionally wherein the electrically conductive material comprises electrically conductive particles, and a second compartment comprising a second collagen scaffold, and wherein the second compartment is disposed on the first compartment and the pores are longitudinally aligned between the compartments. Please see the citations and discussion regarding instant claim 1 for the supporting rejection text.
Weisgerber et al. is in the art of collagen-glycosaminoglycan (collagen-GC) scaffolds, and the introduction of calcium phosphate (CG-CaP) within two discrete compartments (see abstract within Weisgerber et al.). The two compartments have different collagen-based scaffolds and the two compartments are joined by a continuous interface (see abstract within Weisgerber et al.). This supports the different concentrations of the collagen-based scaffolds.
In addition, Wei is in the field of a multicompartment scaffold (polymer cell scaffolds with parenchymal cells; see page 39, lines 14-15 within Wei; also see PTO-892 NPL X) (…the porous biodegradable graft body may be a single or multicompartment structure…; see page 25, lines 11-12 within Wei). Wei discloses both a distinct first and second compartment. For example, an angiogenic growth factor may be provided with the first compartment and an osteoinductive growth factor may be provided with the second compartment (see page 29, lines 10-12 within Wei). Although the Wei reference is not in the collagen scaffold art with an electrically conductive material, this citation provides the skilled artisan (POSITA) the framework to provide the necessary composition taught by Harley et al., Yow et al., and Alegret et al. Implementation of the collagen-based scaffold for purposes of tissue engineering could be envisioned within muscle and tendons as opposed to osteoinductive medicinal aspects of health.
The combination of the Weisgerber et al. and Wei references provide the instant claim limitations that make the present invention obvious.
Regarding instant claim 4, Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei teach wherein a collagen concentration of the first collagen scaffold varies as compared to a collagen concentration of the second collagen scaffold. Please see the citations and discussion within instant claim 2 for the necessary rejection text.
Regarding instant claim 5, Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei teach wherein the collagen concentration for the first collagen scaffold ranges from about 0.5 weight percent (wt%) to about 1.5 wt% and the collagen concentration for the second collagen ranges from about 1.5 wt% to about 5 wt%. Please see the citations and discussion within instant claim 2 for the necessary rejection text. Weisgerber et al. disclose fabrication of CG and CG-CaP precursor suspensions CG scaffolds were afforded from a suspension consisting of 0.5 w/w% type I collagen from bovine Achilles tendon (Sigma-Aldrich, St. Louis, MO) and 0.044 w/w% chondroitin sulfate from shark cartilage (Sigma-Aldrich, St. Louis, MO) in 0.05 M acetic acid (see page 27, left column, 2.1 Fabrication of scaffolds within Weisgerber et al.). Thus, maintaining a constant level collagen within the scaffolds. However, this instant claim limitation would be met under routine experimental procedures by a skilled artisan (POSITA) depending upon the tissue or biological material of choice.
Regarding instant claim 30, Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei teach wherein cells are seeded to the composite, optionally wherein the cells comprise muscle-derived cells (including myoblasts and satellite cells), fibroblasts, neural cells (including neural stem cells, motor neurons), and combinations thereof. Harley et al. disclose the scaffold can be populated by a variety of cells (see paragraph [0032] and abstract within Harley et al.). Additionally, Wei discloses that the mesh (as part of the multicompartment invention) material further may be loaded with cells, growth factors, or bioactive agents (see page 27, lines 9-10; also see abstract; both within Wei). Therefore, a skilled artisan (POSITA) would rely on both the Harley et al. and Wei references to incorporate cells into the overall scaffold.
Analogous Art
The combination of the Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei references are relevant for the rejection of instant claims 1-7 and 28-30 due to their direct application to the present invention.
Obviousness
It would have been prima face obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the collagen-CG scaffold disclosed by Harley et al., using the teachings of Yow et al., Alegret et al., Weisgerber et al. and Wei to incorporate the necessary claim limitations. The motivation to combine the Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei references relies on the common underlying thread of a biological scaffold. Harley et al., Yow et al., Alegret et al. support the fabrication of the instant claim 1 conductive scaffold material. While the Weisgerber et al. and Wei references cite examples of distinct multicompartment scaffolds for treating biological issues.
Starting with Harley et al., the skilled person only had to try the necessary claimed limitations disclosed by Yow et al., Alegret et al., Weisgerber et al. and Wei. The combination of Harley et al., Yow et al., Alegret et al., Weisgerber et al. and Wei would allow one to arrive at the present application without employing inventive skill. This combination of the collagen-CG scaffold taught by Harley et al. along with the necessary use of the claimed limitations taught by Yow et al., Alegret et al., Weisgerber et al. and Wei would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the collagen-CG scaffold disclosed by Harley et al. with the use of the necessary claimed limitations disclosed taught by Yow et al., Alegret et al., Weisgerber et al. and Wei. This combined modification would have led to an enhanced multicompartment collagen-CG conductive scaffold, and thus beneficial for patients.
Conclusion
No claims are allowed.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615