DETAILED ACTION
Claims 1-15, 17-32, 35, and 37 are cancelled.
New claims 39-53 are added.
Claims 16, 33-34, 36 and 38-53 are pending.
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
In the reply filed on 06/24/2025, applicants elected group II, claims 16, 33-34, 36, and 38. Applicant has added new claims 39-53 which are directed to the subject matter of the elected invention. Election was made without traverse in the reply filed on 06/24/2025.
Priority
This application is a 371 of PCT/US2021/025014 which claims benefit of 63/002,273 filed 03/30/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/09/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claims 16, 33-34, 36, 38, 40-43, and 45-53 are rejected under 35 U.S.C. 103 as being unpatentable over Paten, US 20170360986 A1 (see form PTO-892 Notice of References Cited), in view of Hayashi1 (see form PTO-892 Notice of References Cited).
Regarding claim 16, Paten claims the following method:
A method of promoting collagenous tissue remodeling in a subject in need thereof, the method comprising the steps of: (a) administering to a tissue remodeling site in the subject a tissue remodeling solution; and (b) inducing strain or strain rate at the tissue remodeling site, whereby collagen incorporation, collagen fibril assembly, collagen fibril fusion, and/or collagen fibril disassembly is stimulated at the tissue remodeling site (Paten, claim 1).
The method of claim 1, wherein the tissue remodeling solution comprises a mixture of collagen monomers and/or oligomers and is devoid of pre-existing collagen fibrils (Paten, claim 2).
Paten additionally teaches that the tissue remodeling solution further comprises one or more factors that delay collagen assembly or increase a collagen solubility limit. Paten teaches that one of the factors that delay collagen assembly is glucose (Paten, claims 4-6). Glucose is a saccharide. Paten further teaches that the remodeling solution comprises a total collagen concentration is preferably in the range from about 0.001mg/mL to about 50 mg/mL, or about 5 mg/mL to about 50 mg/mL (Paten, [49]). Paten additionally teaches that the subject is a human (Paten, claim 23).
Regarding instant claims 33 and 41, Paten teaches that the remodeling solution comprises a total collagen concentration is preferably in the range from about 0.001mg/mL to about 50 mg/mL, or about 5 mg/mL to about 50 mg/mL (Paten, [49]).
Regarding claim 34 and 38, Paten teaches that the step of administering comprises the use of a wearable device comprising an infusion pump, a reservoir containing the remodeling solution, a catheter implanted at the tissue remodeling site, and a control module programmed to perform the administering (Paten, claim 20). This is interpreted to read upon the limitation of “a medical device comprising the tissue remodeling solution” and the kit as recited in instant claims 34 and 38 respectively.
Regarding claims 36, Paten teaches that the method includes the step of performing the in vitro method of producing one or more collagen fibrils while the collagen monomer solution is in a mold, wherein the shape of the mold provides the shape of the tissue scaffold (Paten, claim 97; [10]). The mold comprising the collagen monomer solution is interpreted to read upon the tissue scaffold or artificial collagen-based tissue.
Regarding claim 42, Paten teaches that the pH of the collagen tissue remodeling solution is 7.7 (Paten, [67]).
Regarding claims 43-44, Paten teaches that the collagen used for the tissue remodeling solution is extracted using acetic acid (acetate) (Paten, [67]). Paten teaches that acetic acid is residually present in the tissue remodeling solution and therefore must be neutralized prior to use (Paten, [67]). Although there may not be a significant amount of acetate in the tissue remodeling solution, the residual acetate is nonetheless present in the solution, and therefore reads upon the limitations of claims 43-44.
Regarding claim 45, Paten teaches that the tissue remodeling solution comprises hyaluronic acid (Paten, claim 4; [12]).
Regarding claim 46, Paten teaches that the tissue remodeling solution comprises one or more factors that delay collagen assembly or increase a collagen solubility limit (Paten, claim 5). Paten further teaches that the one or more above factors are selected from the group consisting of glucose, heat shock proteins, L-arginine, polyarginine, polyglutamine, and anionic polymers (Paten, claim 6). Therefore, in certain embodiments of the invention disclosed by Paten, glucose may be used as the only collagen solubility enhancer in the tissue remodeling solution, which meets the limitations of claim 46.
Regarding claim 47, Paten teaches that the tissue remodeling solution comprises a mixture of collagen monomers, dimers, trimers, aggregates, and/or fibrils (Paten, claim 3).
Regarding claim 48, patent teaches that above method is applied following surgical repair of a torn or severed tendon or ligament, or a broken bone (Paten, claim 41). Paten additionally teaches that the method is applied in connection with orthopedic surgery, arthroplasty, orthodontic surgery, vascular surgery, cosmetic surgery, or skin surgery (Paten, claim 42).
Regarding claim 49, Paten teaches that the tissue remodeling solution is administered by one or more injections or by continuous or intermittent infusion (Paten, claim 10). Paten additionally teaches that the tissue remodeling solution may be applied to the tissue remodeling site via delivery catheter injection at or near the tissue remodeling site (Paten, claim 70).
Regarding claim 50, Patent teaches a programmable control module for controlling the composition of the tissue remodeling solution (Paten, claim 48). Paten teaches that this control module controls the pH, and/or the ionic strength of the tissue remodeling solution (Paten, claims 48, 49, 51). Paten teaches that this control module comprises additional reservoirs for one or more additional reagent solutions and a mixing system for mixing one or more additional reagent solutions with the tissue remodeling solution prior to its transport to the tissue remodeling site (Paten, claim 49). This is considered to be a step of adjusting pH, and/or ionic strength of the repair solution as recited in instant claim 50).
Regarding claim 51, Paten teaches that the above method accelerates the natural healing process (Paten, claim 46; abstract).
Regarding claim 52, Paten teaches that the above method achieves repair of a strain, sprain, tear or rupture of a tendon or ligament (Paten, claim 36). Paten additionally teaches that the above method achieves healing of a fractured or broken bone (Paten, claim 39). Paten additionally teaches that the above method promotes scarless wound healing (Paten, claim 45).
Regarding claim 53, paten teaches that the tissue repair site (referred to as “tissue remodeling site” by Paten) may be a wound (Paten, claim 44). Paten additionally teaches that the tissue repair site may be suspected of being subject to future injury or tissue damage (Paten, [11]).
However, while patent teaches that the remodeling solution comprises a saccharide (i.e., glucose), Paten does not teach the concentration of said saccharide.
Regarding claims 16, 33, and 40, Hayashi teaches that increasing glucose concentration in a solution comprising glucose and collagen increases collagen solubility (Hayashi, Fig. 2). Hayashi demonstrates this relationship in Fig. 2 shown below:
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As shown above, the opacity of the solution decreases as glucose concentration increases. Additionally, Fig. 2 from Hayashi demonstrates that increasing glucose concentration in the solution results in a decreased rate of collagen fibril formation.
It would have been obvious before the date of filing to one of ordinary skill in the art to combine the teachings of Paten and Hayashi. Specifically, it would have been obvious to perform the method taught by Paten with a glucose concentration of at least 0.1 M based on the teachings of Hayashi above. One of ordinary skill in the art would be motivated to use such a glucose concentration in the tissue remodeling solution because Paten teaches that the tissue remodeling solution comprises one or more factors that delay collagen assembly or increase a collagen solubility limit, such as glucose (Paten, claims 5-6). However, Paten does not teach the concentration of glucose present in the tissue remodeling solution, and therefore, in order to practice the method taught by Paten, one of ordinary skill must choose a glucose concentration. Additionally, one of ordinary skill in the art would have a reasonable expectation of success in using a glucose concentration above 0.1 M. As shown in Fig. 2 above, Hayashi teaches that a glucose concentration above 0.1 M significantly increases solubility of collagen, and reduces the rate of collagen fibril formation. Therefore, it would have been obvious before the time of filing to combine the above teachings of Paten and Hayashi.
Claims 16, 33-34, 36, 38-39, and 41-53 are rejected under 35 U.S.C. 103 as being obvious over Paten (cited above), in view of Im2 (see form PTO-892 Notice of References Cited).
The teachings of Paten as they relate to claims 16, 33-34, 36, 38, and 41-53 are shown above. Paten does not teach that the repair solution (remodeling solution) comprises one or more saccharides at a concentration of at least about 0.01 M. Paten does not teach that the repair solution comprises one or more of the saccharides recited in claim 39.
Im teaches that chondroitin sulfate is composed of repeating units of D-glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc) (Im, pg. 109, right column, section 3). Im also teaches that Hyaluronic acid consists of N-acetyl-D-glucosamine and glucuronic acid (Im, pg. 111, left column, section 5). Im teaches that hyaluronic acid and chondroitin sulfate are glycosaminoglycans (GAGs) (Im, pg. 106, abstract).
It would have been obvious before the date of filing to one of ordinary skill in the art to modify the method taught by Paten based upon the teachings of Im. Specifically, it would have been obvious to include N-acetyl-D-galactosamine, glucuronic acid, and/or N-acetyl-D-glucosamine in the tissue remodeling solution used in the method taught by Paten. One would have been motivated to make the above modification because Paten teaches “The approach described herein regulates the molecular environment of a tissue undergoing repair or remodeling by delivering an exogenous mixture of biomolecules and/or their precursors to alleviate the burden and reliance placed on the endogenous biological response. The components of the mixture are similar to those present during wound healing and/or tissue development. Additional components, such as anti-inflammatory molecules or immune suppressing molecules, can also be included. The mixture of molecules contributes to and accelerates the repair process” (Paten, [4]). As shown above, Im teaches that N-acetyl-D-galactosamine, glucuronic acid, and/or N-acetyl-D-glucosamine are precursors to hyaluronic acid and chondroitin sulfate. Furthermore, one of ordinary skill in the art would have a reasonable expectation of success in making the above modification because Im teaches that hyaluronic acid, and chondroitin sulfate are used in hydrogels to increase/enhance wound healing (Im, pg. 111, left column, [3]; pg. 109, right column, section 3). One of ordinary skill in the art would have a reasonable expectation of success in using the precursor molecules (i.e., N-acetyl-D-galactosamine, glucuronic acid, and/or N-acetyl-D-glucasamine) to enhance wound healing by delivering said precursors to alleviate the burden and reliance placed on the endogenous biological response, as taught by Paten. Additionally, regarding the limitation of “one or more saccharides at a concentration of at least about 0.01 M” in claim 16, MPEP section 2144.05(II)(A) states “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”. The teachings of Paten and Im make it obvious to one of ordinary skill to include the above precursor molecules in the tissue remodeling solution. The limitation of the saccharide concentration being at least about 0.01 M is the result of routine optimization, as one of ordinary skill in the art would be capable, and have a reasonable expectation of success, in adjusting the saccharide concentration to determine the optimal concentration for wound healing. Therefore, the teachings of Paten and Im render claims 16, 33-34, 36, 38-39, and 41-53 obvious.
Conclusion
No claims are allowed.
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/BENJAMIN HALL EASTON/Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
1 Hayashi T, Nagai Y. Factors affecting the interactions of collagen molecules as observed by in vitro fibril formation. I. Effects of small molecules, especially saccharides. J Biochem. 1972 Sep;72(3):749-58. doi: 10.1093/oxfordjournals.jbchem.a129953. PMID: 4673764.
2 Im, A.-R., & Kim, Y. S. (2009). Role of Glycosaminoglycans in Wound Healing. Arch Pharm Sci & Res , 1(2), 106–104. http://www.apsronline.com/Documents/October%202009/01022009002.pdf