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 .
Status of claims
Claims 1, 3, 5-6, 8-14, 16-18, and 20 are original. Claims 2, 4, 7, 15, and 19 are currently amended. Claims 1-20 are pending and under examination.
Priority
This application is a 371 of PCT/US2023/020145, filed on 04/27/2023. This application claims the benefit of U.S. Provisional Application No. 63/335,235 filed on 04/27/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/27/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 10, 12, 15, and 20 are objected to because of the following informalities:
Claim 10 is objected to for each formula ending in “4” where it should be a subscripted as “4”.
Claim 12 recites “average molecular weight 1800”. Proper syntax is “average molecular weight of 1800”.
Claim 12 recites “average diameter 0.1 to 100 micrometers”. Proper syntax is “average diameter of 0.1 to 100 micrometers”.
Claim 15 has a comma (“,”) at the end of the statement rather than a period (“.”).
Claim 20 recites “or other tissue” in multiple locations. Proper syntax is “or other tissues”.
Appropriate correction is required.
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 1-20 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.
The term “low swelling” in claim 1 is a relative term which renders the claim indefinite. The term “low swelling” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 1 recites the limitation "providing the triblock copolymer" in the claim with the prior recitation being “triblock copolymers”, which is multiple form. It is unclear which of the triblock copolymers that “the triblock copolymer” is. There is insufficient antecedent basis for this limitation in the claim. Applicant may amend this recitation to “providing the triblock copolymers”.
Claims 2-20 are also rejected as being dependent on indefinite claim 1.
Claim 8 recites an “average molecular weight 1800”. However, no unit (e.g., Da, kDa) is provided to define the molecular weight, thus rendering the claim indefinite. It will be assumed that the unit for molecular weight is in Da.
Claims 8 and 10 recite the symbols m, n, and/or p in their structural formulas. However, it is not specified what number or range of numbers are represented by each of these symbols (e.g., “m=1-100, n=5-10, p=2-7”, etc.), thus rendering these claims indefinite.
Claim 11 is also rejected as being dependent on indefinite claim 10.
Claim 13 does not clarify whether the list of polymers is alternative (i.e., “or”) or conjunctive (i.e., “and”), thus rendering it indefinite as to whether only one or all of the listed polymers are required. It will be assumed that only one of the polymers are required.
Claim 20 recites “incising the skin of a subject exposing a bone”. It is unclear whether the bone of the subject was already exposed before incision or the incision resulted in the bone exposure, rendering the claim indefinite. A suggested amendment is to alter the language to “incising the skin of a subject and thereby exposing a bone”.
Claim 20 recites phrases such as “removed/exposed bone” and “inserted/fixed/transplanted bone”. It is unclear whether the words separated by each “/” are either alternative to one another or are being denoted as different words having a similar meaning (i.e., synonyms), thus rendering the claim indefinite. A suggested amendment is to alter the claim language to “removed or exposed bone” and “inserted, fixed or transplanted bone”.
Claim 20 recites “optionally inserting and/or fixing a biocompatible device…; and implanting a biodegradable implant…”. It is unclear whether “implanting a biodegradable implant…” is also an optional limitation of the claim, or if it is required––thus rendering the claim indefinite.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-8 and 12-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hunter et al. (US20050148512A1) in view of Macdougall et al. (Macdougall LJ, Pérez-Madrigal MM, Arno MC, Dove AP. Nonswelling Thiol-Yne Cross-Linked Hydrogel Materials as Cytocompatible Soft Tissue Scaffolds. Biomacromolecules. 2018;19(5):1378-1388. doi:10.1021/acs.biomac.7b01204).
Hunter et al. discloses pharmaceutical compositions, methods and devices, and more specifically, to compositions and methods for preparing medical implants to make them more adherent to, or, more readily incorporated within a living tissue [¶3].
Regarding Claim 1, Hunter et al. teaches that the composition may be biodegradable [¶150]. Hunter et al. teaches that the composition may comprise therapeutic agents incorporated into swellable, biomimetic polymers used to create an artificial nucleus pulposus tissue that expands in situ to conform to the natural size and shape of the intervertebral disc [¶326], and can specifically be in the form of implantable and swellable hydrogels [¶¶ 53, 270, 272, 770]. Hunter et al. teaches that the polymeric carriers of the composition may provide sustained release of the active agents [¶¶997, 998]. Hunter et al. teaches that the composition may include dexamethasone as a cell proliferative agent (rendering it a fibrotic agent per ¶39) and an anti-inflammatory agent [¶¶16, 55].
Regarding claims 1, 2, and 4, these partially (i.e., claim 1) or fully (i.e., claims 2 and 4) comprise product-by-process elements, and shall be examined as such. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based only on the product itself, per MPEP 2113. When the prior art teaches the product limitations regarding structure and ingredients, then it will read on the claim.
Regarding claim 3, the elements are considered a post-use characteristic, and therefore bear no patentable weight. As the prior art leads to a materially similar product, it is capable of such a function.
Regarding claims 5 and 6, Hunter et al. teaches that the composition may include dexamethasone as a cell proliferative agent (rendering it a fibrotic agent per ¶39) and an anti-inflammatory agent [¶¶16, 55].
Regarding claim 12, Hunter et al. teaches that the therapeutic compositions may be fashioned in any size ranging from 50 nm to 500 μm, with such compositions in the form of microspheres (porous or non-porous), microparticles, and/or nanoparticles [¶134].
Regarding Claim 13, Hunter et al. teaches that PLGA can be the carrier of such active agents [¶183].
Regarding claims 14 and 16, Hunter et al. teaches that the fibrosing agent or a composition comprising the fibrosing agent may be combined with a film or mesh or may be in the form of a film or mesh [¶136], with meshes being surgical patches [¶137] that are sufficiently flexible to conform to the shape of a device surface or an anatomical surface [¶144]. Hunter et al. teaches that one or all side of the mesh can be coated with the composition (containing the anti-inflammatory agent) [¶157].
Regarding claim 15, Hunter et al. teaches that medical devices including implants such as screws and plates [¶38] may be coated with such polymeric gels (and the gel may be on one side of the said mesh) [¶59]. Additionally, claim 15 is dependent to an optional component of claim 14, which would render its elements optional as well.
Regarding claims 17 and 19, Hunter et al. teaches that the composition may be coated into the implant and injected into an intervertebral disc space (which would thus contact the two surround vertebras), and also may be coated on implanted spinal fusion devices (e.g., the BAK/C Cervical Interbody Fusion System and the CERVI-LOK Cervical Fixation System; which bridge, stabilize, and join two or more vertebrae) [¶¶18, 38, 45, 261, 307-319]. These teachings obviate the method of present claim 19, as utilizing one of these devices and methods coated with the dexamethasone-containing composition (which may treat dysphagia per the present specification ¶¶04, 17) would have inherently treated post-operative dysphagia.
Regarding claim 18, Hunter et al. teaches that combinations of anthracyclines (e.g., doxorubicin) and antibiotic and/or antifungal agents can be utilized in the composition to enhance the antibacterial activity of the implant [¶107].
Regarding claim 20, Hunter et al. discloses surgical procedures involving incision and exposure of spinal tissues such as the bone, vertebrae, intervertebral disc, annulus, dura, and nerve root structure [¶279-280]. Hunter et al. further teaches that cervical and thoracic disks excisions may be performed as an anterior discectomy with fusion [¶280], and that the disclosed composition (which would contain dexamethasone as a sustained-release anti-inflammatory agent as previously stated) is delivered (implanted) under direct vision during open or endoscopic disc excision and applied directly to the annulus or dural defect at the exposed surgical site [¶281], which would suggest reduced swelling, pain, and inflammation at a surgical site by applying a therapeutic composition to exposed spinal tissue during surgery, as recited in present claim 20.
However, Hunter et al. does not teach the partial limitation of claim 1, wherein “the hydrogel comprises triblock copolymers comprising of two hydrophilic side chains and a central hydrophobic chain and terminal thiol groups which are crosslinked by a multi-arm linker”, nor does it teach the limitations of claims 7-8.
Macdougall et al. discloses cyto-compatible and non-swellable thiol-yne click-hydrogels prepared from alkyne- and thiol-functionalized PEG precursors for use in soft tissues [title and abstract]; Macdougall et al. expressly teaches that the thermo-responsive non-swellable click hydrogels were synthesized using a “thiol-terminated Pluronic PEG precursor, PEG-PPG-PEG (2900 g/mol, Pluronic L-64, 40% of ethylene glycol content),” thereby teaching a PEG-PPG-PEG triblock copolymer having two hydrophilic PEG side-chains and a central hydrophobic PPG chain, as well as the Pluronic L-64 structure having 40% ethylene glycol content as recited in claim 8 [p. 1381, column 2, ¶2]. In this case, the, the polypropylene glycol has a molecular weight of 1740 Da, which is less than a 4% difference from the claimed 1800 Da––per MPEP 2144.05, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. In this case, "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties” (see MPEP 2144.05, Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)). Macdougall et al. further confirms the terminal thiol functionality in the synthesis section titled “synthesis of 2-arm Thiol-functionalized Pluronic L-64 (PEG-PPG-PEG 2.9 kg/mol),” which states that PEG-PPG-PEG was esterified with 3-mercaptoproprionic acid and that 1H NMR showed about 93% conversion of hydroxyl groups to mercaptopropionate groups [p. 1380, column 1, lower third]. Scheme 2(b) visually depicts the corresponding “2-arm PEG-PPG-PEG (3 kg/mol)” precursor with terminal “HS” groups at both ends [p. 1382, scheme 2(b)]. Macdougall et al. also teaches the multi-arm PEG linker/crosslinking aspect because scheme 2(a) depicts 3-arm PEG and 4-arm PEG precursors, the text states that 3-arm and 4-arm PEG polymers were functionalized with propiolic acid or mercaptopropionic acid, and the hydrogel fabrication states that click-hydrogels were prepared by mixing solutions containing a 1:1 molar ratio of alkyne to thiol end groups in PBS pH 7.4 [p. 1381, column 2, ¶2; p. 1382, scheme 2(a); p. 1380, column 2, “hydrogel fabrication”].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the implantable, drug-releasing hydrogel composition of Hunter et al. to include the non-swellable thiol-yne PEG-PPG-PEG hydrogel chemistry of Macdougall et al. This is because Hunter et al. teaches implantable hydrogel compositions for sustained therapeutic release and tissue incorporation, while Macdougall et al. teaches cyto-compatible low/non-swelling crosslinked hydrogels formed from thiol-terminated PEG-PPG-PEG triblock copolymers and multi-arm PEG crosslinking precursors. A person of ordinary skill in the art would have thus been motivated to use Macdougall et al.’s non-swellable triblock hydrogel network in Hunter et al.’s implantable therapeutic system to provide a biocompatible drug-releasing hydrogel implant having reduced swelling while maintaining structural integrity and suitability for soft tissue implantation. A person of ordinary skill in the art would have had a reasonable expectation of success doing so because both references are biocompatible hydrogel materials for implantation or tissue-contacting medical applications, and Macdougall et al. expressly demonstrates successful formation of cyto-compatible non-swellable thiol-yne crosslinked PEG-based hydrogels using the claimed triblock copolymer and multi-armed crosslinking chemistry.
Claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Hunter et al. (US20050148512A1) in view of Macdougall et al. (Macdougall LJ, Pérez-Madrigal MM, Arno MC, Dove AP. Nonswelling Thiol-Yne Cross-Linked Hydrogel Materials as Cytocompatible Soft Tissue Scaffolds. Biomacromolecules. 2018;19(5):1378-1388. doi:10.1021/acs.biomac.7b01204) in further view of Jansen et al. (US20180346902A1).
Hunter et al. and Macdougall et al. collectively teach all required limitations of present claims 1-8 and 12-20.
However, Hunter et al. and Macdougall et al. fail to collectively teach all required limitations of present claims 9-11.
Jansen et al. discloses a method to prepare synthetic hydrogels having tissue-specific properties, and a hydrogel comprising a polymer matrix comprising a plurality of peptide. Jansen et al. teaches that such synthetic hydrogels of the invention have increased bio-compatibility as a result of incorporation of tissue specific peptides and tuning of polymer crosslinking into a polymeric hydrogel to match the chemical and mechanical properties of a particular tissue [¶4]. Jansen et al. teaches that the polymer is formed of 2K, 10K, 20K, or 40K PEG star PEG with 4, 6, or 8 arms [¶6], with the molecular wights overlapping with that of claim 11. Jansen et al. teaches that 3D hydrogels were prepared with a 2K, 10K or 20K 4-arm PEG-maleimide, and that the Peg-maleimide was cross-linked at a 1:1 molar ratio with linear PEG-dithiol and MMP-degradable peptide crosslinker, thereby teaching a multi-arm PEG-maleimide based cross-linker as recited in claim 9[¶46]. Jansen et al. also supports claim 10 because the disclosed 4-arm PEG-maleimide corresponds to a multi-arm PEG maleimide cross-linker having maleimide termini on a multi-arm PEG backbone, and Further describes hydrogel formation through maleimide-thiol Michael-type addition, with maleimide selected as the Michael-type acceptor and thiol as the Michael-type donor [¶60].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to further modify the Hunter et al. and Macdougall et al. hydrogel implant system to use the multi-arm PEG-maleimide crosslinker chemistry of Jansen et al. This is because Macdougall et al. already teaches thiol-functionalized PEG-PPG-PEG hydrogel precursors and crosslinking through thiol-reactive end groups, while Jansen et al. teaches that multi-arm PEG-maleimide crosslinkers are suitable for forming biocompatible synthetic hydrogels through maleimide -thiol Michael-type addition. A person of ordinary skill in the art would have thus been motivated to substitute or employ Jansen et al.’s multi-arm PEG-maleimide crosslinker in the combined Hunter et al. and Macdougall et al. hydrogel system to provide a predictable thiol-reactive PEG-based crosslinking mechanism for forming a biocompatible implantable hydrogel with tunable mechanical and tissue-specific properties. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because Jansen et al. expressly demonstrates hydrogel formation using 4-arm PEG-maleimide crosslinked with PEG-dithiol at a 1:1 molar ratio, and Macdougall et al.’s triblock PEG-PPG-PEG precursor already provides terminal thiol functionality suitable for reaction with such maleimide groups.
Conclusion
No claim is found allowable.
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Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/
Primary Examiner, Art Unit 1613
Prosecution Insights