DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Preliminary amendment filed on 11/07/2024 has been entered. Claims 3, 4, 6-8, 15, 24-28, and 30-44 are cancelled. Claims 1, 2, 5, 9-14, 16-23, 29, 45, and 46 are pending in this application and are currently under examination.
Priority
This application is a 371 of PCT/CA2023/050420 filed on 03/29/2023 and claims benefit of US PRO 63/362,057 filed on 03/29/2022.
Information Disclosure Statement
The information disclosure statement (IDS) with appropriate assertion under 37 CFR 1.98 filed on 02/20/2026 has been considered.
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.
Claims 1, 2, 5, 9-14, and 16-19 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. Claims 2, 5, 9-14, and 16-19 depend from claim 1.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Claim 1 recites “substantially homogenous gel” in the two adding steps, indicating that the gel is formed before adding a crosslinking agent or subjecting to resonant acoustic mixing, which contradicts to the recitation “the substantially homogenous gel is produced following resonant acoustic mixing” in claim 5. Also, the “substantially homogenous gel”, an intended consequence of the claimed process, has not been included in the preamble. Applicant is advised to insert the clause “and producing a substantially homogenous gel” immediately after the recitation “crosslinking a polymer” (line 1); and to change the recitation “substantially homogenous gel” (lines 4 and 5) to “gel material”.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
(I) Claims 1, 2, 5, 11, 13, 14, 16-20, and 45 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Southard et al. (US 2017/0035937, Feb. 9, 2017, hereinafter referred to as Southard ‘937).
With regard to structural limitations “a process (or carrying out at room temperature) comprising: adding an aqueous solution comprising a dissolved base (or sodium hydroxide) to a polymer (e.g. cartilage or collagen) to produce a gel material; adding a crosslinking agent (or a bifunctional crosslinking agent) to the gel material to produce a mixture; and subjecting the mixture to resonant acoustic mixing conditions sufficient to effect crosslinking of the polymer; wherein the resonant acoustic mixing conditions comprise a forcing energy ranging between about 20g to about 100g (or further comprising mixing frequencies ranging between about 40 Hz to about 90 Hz; or over a period of time ranging from about 1 minute to about 10 minutes) to produce a substantially (defined as “a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term” in the Specification) homogenous gel (or further comprising a purification step and/or sterilization step or washing the crosslinked polymer using an aqueous hydrochloric acid solution)” (claims 1, 2, 5, 11, 13, 14, and 16-19), and “a product (or a gel) comprising a crosslinked polymer produced by resonant acoustic mixing” (claims 20 and 45):
Southard ‘937 disclosed a methods facilitating tissue homogenization. Processing solutions for tissue homogenization may include any of a saline solution, a buffer solution, an organic acid solution (such as acetic acid and citric acid), a mineral acid solution, an alkaline metal salt solution (such as NaOH and KOH), and water. Exemplary processing solutions are PBS and water. In some instances, the processing solution may be a buffer solution. A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base. In some instances, the processing solution may comprise a cross-linking or fixative agent such as, glutaraldehyde. In some instances, the processing solution may be an acid solution. Acid solutions may include hydrochloric acid (HCl). In some instances, the tissue may be cartilage. Cartilage can be defined as flexible but inelastic cords of strong fibrous collagen tissue. The cells within cartilage tissue are called chondrocytes. These cells generate proteins, such as collagen, proteoglycan, and elastin, that are involved in the formation and maintenance of the cartilage. Homogenized tissue can be combined with bone particles, minced cartilage, or cells, to form a homogenized tissue product in the form of a putty, a paste, or powder having the particulate components uniformly distributed throughout the homogenized tissue. In some instances, homogenized tissue may be combined with any tissue or material so as to improve or enhance the moldability of that tissue or material, for use as a scaffold for implantation at a treatment site within a patient (page 22/42, [0120, 0123, 0127, and 0121]; page 24/42, [0143]; page 26/42, [0158]). Cell Viability Assessment: Samples of 3 8 mmx 1 mm cartilage disks were placed in triplicate in 125 mL sterile plastic specimen cups and filled with of human chondrocyte growth medium. The cups were placed in a LabRAMTM II ResonantAcoustic® Mixer and resonant acoustic energy (RAE) was applied at various settings for different amounts of time (as shown in Table 9 below). The frequency was kept at 60 Hz for all conditions. After processing, the cartilage samples from each condition were placed into 24 well culture plates, covered with fresh chondrocyte growth media. Samples for which the cell count of the processed sample remained about the same as the original cell count (no impact on cell viability) are denoted with "+++". Samples for which the cell count of the processed sample reflected a decrease of 50% or less compared to the original cell count are denoted by "+". Samples that reflected a greater than 50% reduction in cell viability after processing are denoted by"-".
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(page 37/42, [0240, 0243, 0244]). In some instances, the tissue may be articular cartilage. Articular cartilage contains significant amounts of collagen, and cross-linking of the collagen imparts a high material strength and firmness to the tissue (page 24/42, [0143]).
Thus, these teachings of Southard ‘937 anticipate Applicant’s claims 1, 2, 5, 11, 13, 14, 16-20, and 45 because (a) the cartilage or collagen is a polymer, (b) putty or paste after homogenization is a homogenous gel, and (b) the glutaraldehyde is antimicrobial and is a crosslinker. Or, one of skilled artisan would be motivated to modify the processes above to obtain a specific step recited in the dependent claims.
(II) Claims 1, 2, 5, 9-12, 14, 16-18, 20-23, 29, 45, and 46 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Schachar et al. (WO 2022/213101, Oct. 6, 2022, benefited from US PRO 63/169,534 filed on April 01, 2021 and incorporated by reference of US PRO 63/171,232 filed on April 06, 2021, hereinafter referred to as Schachar ‘101).
With regard to structural limitations “a process (or carrying out at room temperature) comprising: adding an aqueous solution comprising a dissolved base to a polymer (or a carbohydrate polymer; or hyaluronic acid) to produce a gel material; adding a crosslinking agent (or a bifunctional crosslinking agent; or 1,4-butanediol diglycidyl ether, BDDE) to the gel material to produce a mixture; and subjecting the mixture to resonant acoustic mixing conditions sufficient to effect crosslinking of the polymer; wherein the resonant acoustic mixing conditions comprise a forcing energy ranging between about 20g to about 100g (or further comprising mixing frequencies ranging between about 40 Hz to about 90 Hz; or over a period of time ranging from about 1 minute to about 10 minutes) to produce a substantially (defined as “a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term” in the Specification) homogenous gel (or further comprising a purification step and/or sterilization step)” (claims 1, 2, 5, 9-12, 14, and 16-18,), and “a product (or a dermal filler; or an injectable dermal filler; or a gel) comprising a crosslinked polymer (or crosslinked hyaluronic acid) produced by resonant acoustic mixing” (claims 20-23, 45, and 46), and “a method comprising administering to a subject in need thereof an effective amount of the injectable dermal filler as defined in claim 23” (claim 29):
Schachar ‘101 disclosed that hydrogel as used herein refers to a network of polymer chains that are hydrophilic and are dispersed within an aqueous medium. A three-dimensional structure can result from the hydrophilic polymer chains being held together by cross-links, ,which may he covalent or ionic crosslinks. In some variations, the hydrophilic polymer may be a hyaluronic acid. In some variations, the hydrophilic polymer may be a modified form of hyaluronic acid. In some instances, the hydrophilic polymer is a collection of hyaluronic acid at different molecular weights. In some instances, the hyaluronic acid is crosslinked. In some instances, the crosslinking ratio adjusted to achieve a biologic effect. In some instances, crosslinking is performed during mixing. Suitable excipients for mixing with the hydrophilic polymer are aqueous excipient which can be sterilized and incorporated into the aseptic manufacturing process. Such aqueous excipient may he acidic, neutral, or basic. In some instances, the pH may be greater than 8. FIG. 6, a graphic representation of an aseptic manufacturing method that uses resonant acoustic mixing to achieve initial material mixing, then diffusion mixing to achieve material homogeneity, then centrifugation to remove entrapped bubbles:
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(page 9/62, [0039]; pages 13/62 to 14/62, [0052 and 0054]; page 8/62, [0023]; page 48/62, Figure 6). in some instances, the pharmaceutical product is a crosslinking agent. Such cross-linking agents include 1,4-butanediol diglycidyl ether (BDDE), divinyl sulfone (DVS). in some variations, the vibratory mixing may have a frequency of about 50 Hz or about 60 Hz. in some variations, applying acoustic forces may include a linear acceleration of about 60 g, about 80g, or about 100g. In some variations, applying the resonance acoustic forces may be performed for a period of time of about 1 min, about 10 min (page 25/62, [0074]; ,page 32/62, [0106, 0107, and 0108]). A prefilled syringe is described in U.S. provisional application 63/171,232 entitled A PREFTLLED SYRINGE CONTAINING STERILE ULTRACONCENTRATED HYDROGEL, the entire contents of which are hereby incorporated by reference (page 40/62, [0151]). The 63/171,232 (also published in WO2022217194, Oct. 13, 2022) disclosed in some embodiments that the hydrogel is cross-linked. In some embodiments, the hydrophilic polymer is hyaluronic acid In some variations, the syringe is used to inject the ultraconcentrated hydrogel into the dermal space. In some variations, the syringe is used to inject the ultraconcentrated hydrogel into a biologic implant located within a biologic tissue. In some variations, the implant is located or around the eye (pages 9/26 to 10/26, [0041]; page 25/26, [0081]).
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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