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 .
Status of the Claims
Claims included in the prosecution are claims 1-2 and 5-18. Claims 3-4 are cancelled. Claims 7-18 have been added.
Priority
This application is a 371 of PCT/US2022/025315 filed 04/19/2022 which claims benefit of 63/177,373 filed 04/20/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 10/02/2023 and 02/24/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, this IDS has been considered by the Examiner.
Claim Objections
Claim 12 is objected to because of the following informalities: it appears that the term “polymer” should be plural. Appropriate correction is required.
Claim 15 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 7. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. MPEP § 608.01(m).
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(s) 9 and 13 is/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.
Claim 9 recites the limitation "the cargo" in line 2 of claim 9. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether or not the cargo of claim 9 is the therapeutic cargo (i.e., instant claim 8) or a different cargo.
Claim 13 recites “frequency range from 10-1 rad/s to 10 rad/s.” It is not clear what is meant by “10-1” thereby making the lower end value of the range unclear and thereby rendering the modulus limitations of the claim indefinite. For the purposes of this Office Action, prior art teaching a storage modulus (G’) greater than a loss modulus (G”) meets the claim limitation.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 5-6 and 13 and is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lyu et al. (Liposome Crosslinked Polyacrylamide/DNA Hydrogel: a Smart Controlled-Release System for Small Molecular Payloads. Small, 14, 1704039, Feb. 26, 2018, as cited on IDS) evidenced by Poocza et al. (Hydrophobic Cholesteryl Moieties Trigger Substrate Cell–Membrane Interaction of Elastin–Mimetic Protein Coatings in Vitro. ACS Omega 2019 4 (6), 10818-10827, Jun. 21, 2019).
Lyu et al. disclose a novel stimuli-responsive hydrogel system with liposomes serving as both noncovalent crosslinkers and functional small molecules carriers for controlled-release wherein liposomes can crosslink polyacrylamide copolymers functionalized with cholesterol-modified DNA motifs to yield a DNA hydrogel system, due to the hydrophobic interaction between cholesteryl groups and the lipid bilayer of liposomes (abstract). As evidenced by Poocza et al., cholesteryl groups are hydrophobic (title, abstract) to anticipate claim 5 (i.e., hydrophobic chemistries) and further anticipate claim 6 (i.e., alkyl). Here the prior art anticipates the hydrogel noncovalently crosslinked with hydrophobic functionalized polymer with liposomal nanoparticle crosslinkers of instant claim 1. Regarding claim 13, Lyu et al. discloses G′ as higher than G″ (page 3 of 8, column 1, paragraph 2).
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 5-6 and 12-14 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Lyu et al. (Liposome Crosslinked Polyacrylamide/DNA Hydrogel: a Smart Controlled-Release System for Small Molecular Payloads, Small, 14, 1704039, Feb. 26, 2018, as cited on IDS) evidenced by Poocza et al. (Hydrophobic Cholesteryl Moieties Trigger Substrate Cell–Membrane Interaction of Elastin–Mimetic Protein Coatings in Vitro. ACS Omega 4 (6), 10818-10827, Jun. 21, 2019).
Lyu et al. disclose a novel stimuli-responsive hydrogel system with liposomes serving as both noncovalent crosslinkers and functional small molecules carriers for controlled-release wherein liposomes can crosslink polyacrylamide copolymers functionalized with cholesterol-modified DNA motifs to yield a DNA hydrogel system, due to the hydrophobic interaction between cholesteryl groups and the lipid bilayer of liposomes (abstract). As evidenced by Poocza et al., cholesteryl groups are hydrophobic (title, abstract, pg. 10819, Scheme 1., CTA) to read on the hydrophobic functionalized polymer of instant claim 1, alkyl groups of instant claim 6 thereby meeting the limitation of instant claim 5. The hydrogel exhibits injectable property as well as self-recovery behaviors (abstract). The hydrophobic effect as the main driven force in the solution-to-gel process, and the dynamic crosslinking may facilitate the formation of injectable hydrogels is known in the art (page 1 of 8, column 2, paragraph 2).
Lyu et al. teach a hydrogel formed by mixing the DNA copolymer and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposome solution and driven by the hydrophobic interaction between the cholesteryl group and the lipid bilayer (page 1 of 8, column 2, paragraph 3). A liposome crosslinked with responsive DNA hydrogel is provided to realize the controlled-release of functional small molecular payloads (page 1 of 8, column 2, paragraph 3).
Regarding claims 12-13, Lyu et al. disclose that for all the hydrogels with different DNA: acrylamide ratios at low strain region (0.1–30%), the values of G′ and G″ were constant, and G′ was higher than G″ revealing a gel state (page 3 of 8, column 1, paragraph 2) to read on a storage modulus greater than the loss modulus limitation of instant claim 13. The percent range taught here encompasses the 2 wt% of functionalized polymer limitation of instant claim 12.
Regarding claims 14, Lyu et al. teach that the hydrogel also showed self-recovery and viscous flow under shear stress (page 2 of 8, column 1, paragraph 1).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to employ the hydrogel system taught by Lyu et al. with expected results. One would be motivated to do so because Lyu et al. with evidence from Poocza et al. teach a system that has self-healing and injectable properties as well as good biocompatibility thereby making it well suitable for a variety of in vitro and in vivo biomedical applications (pg. 5, see Conclusion).
Claim(s) 2, 7-11 and 15-18 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Lyu et al. (Liposome Crosslinked Polyacrylamide/DNA Hydrogel: a Smart Controlled-Release System for Small Molecular Payloads, Small, 14, 1704039, Feb. 26, 2018, as cited on IDS) evidenced by Poocza et al. (Hydrophobic Cholesteryl Moieties Trigger Substrate Cell–Membrane Interaction of Elastin–Mimetic Protein Coatings in Vitro. ACS Omega 4 (6), 10818-10827, Jun. 21, 2019) as applied to claims 1, 5-6 and 12-14 above, and further in view of Appel et al. (US20170319506 A1, Nov. 9, 2017).
The teachings of Lyu et al. and Poocza et al. are discussed above.
Regarding claim 2, Lyu et al. differ from the claimed invention wherein the polymers functionalized with hydrophobic fatty pendant groups are dodecyl-modified hydroxypropyl methyl cellulose (HPMC).
However, Appel et al. teach n-dodecyl-capped HPMC ([0136]). Appel et al. teach network materials that have both shear thinning and self-healing properties (abstract). The networks are useful for a variety of biomedical uses, including drug delivery (abstract). Hydrophobically-modified gel-forming polymers are disclosed wherein the capping group contains linear alkyl groups, such as, for example, but not limited to, n-dodecyl ([0096]; see Example 3 (n-dodecyl-capped HPMC) ([0136]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to substitute the polyacrylamide/DNA copolymer of Lyu et al. with the HPMC/n-dodecyl of Appel et al. for a similar purpose of providing a functionalized polymer that hydrophobically interacts with liposomal nanoparticle crosslinkers. Simple substitution of one hydrophobically functionalized polymer for another is within the purview of the skilled artisan and would yield predictable results. And also, Appel et al. provide data to demonstrate gels with HPMC-C12 exhibiting exceptionally fast and complete recovery of properties in a matter of a few seconds after stress-induced flow ([0143]). Moreover, the rate and extent of recovery is unchanged over several cycles of breaking and reforming, highlighting the reversible and robust nature of the non-covalently cross linked hydrogel structure (FIG. 2h) suggesting enhanced injectability ([0143]).
Regarding claims 7-11, Lyu et al. disclose the controlled release of functional small molecular payloads carried by the liposomes (title, abstract) but the cargo is not therapeutic. Nevertheless, Lyu et al. differ from the claimed invention wherein the injectable hydrogel network further comprises a therapeutic cargo carried by the liposomal nanoparticles.
However, Appel et al. teach therapeutic cargo in a liposome. Appel et al. disclose many and varied therapeutic agents that can be incorporated int the particle/hydrogel ([108]). A schematic representation of two stage release of teach therapeutic cargo allowing for facile tuning of drug release profile is provided ([0018]; FIG. 3, see cargo-loaded particles). Notably Appel et al. disclose therapeutic fluorescence ([0024]) and fluorescent dyes ([0126]) to echo the DilC18(5)-calcein pair taught by Lyu et al.
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to apply the teachings of therapeutic cargo by Appel et al. to Lyu et al. with expected results. One would be motivated to do so because Appel et al. teach that the compositions can contain one or more therapeutic, prophylactic and/or diagnostic agents; the agent can be a small molecule ([0107]). Exemplary diagnostic agents include fluorescent compounds ([0112]). The combined prior art of Lyu et al. and Appel et al. reads on the injectable hydrogel network further comprising a therapeutic cargo carried by the liposomal nanoparticles of instant claim 7.
Regarding claims 8 and 9, as mentioned above, Lyu et al. teach phospholipid systems wherein DOPC (i.e., phosphatidylcholines (PCs), phospholipid) is configured to interact with cargo (DiIC18(5)) and calcein (see section 1. Introduction). Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art to combine the teachings of Lyu et al. and Appel et al. to have arrived at an injectable hydrogel comprising phospholipids with affinity motifs configured to interact with therapeutic cargo.
Regarding claim 10, Lyu et al. shows in Figure 1 that there were boundaries between the gel, solution, and precipitate phases (page 2 of 8, column 2, paragraph 1; Fig. 1. d) see hydrogel). Appel et al. teach interactions between polymers and nanoparticles include electrostatic interactions ([0099]; Fig. 7 and 9). Here the teachings in the prior art read on the electrostatic interaction of instant claim 10.
Regarding claim 11, Lyu et al. provided studies to show binding and retaining into the lipid bilayers of liposomes to form a highly crosslinked uniform network structure (page 3 of 8, column 1, paragraph 1). The strength of these non-covalent interactions depend on the surface area and polarization of the hydrophobic capping groups (see Appel et al. [0097]) is art-known. Appel et al. disclose agents can be encapsulated within the particles, associated with the surface of the particles and/or be dispersed through the hydrogel ([0114]). Here the combined teachings of Lyu et al. and Appel et al. read on the nanoparticles have a surface chemistry configured to interact with the therapeutic cargo limitation of instant claim 11.
Regarding claims 15-18, as mentioned above, Lyu et al. disclose the controlled release of functional small molecular payloads carried by the liposomes (title, abstract) but the cargo is not therapeutic. Again, Lyu et al. differ from the claimed invention wherein the injectable hydrogel network further comprises a therapeutic cargo.
Appel et al. teach cytokines as exemplary therapeutic agents that can be incorporated into the particles/hydrogel ([0108]) to read on cytokine species of claim 17, the protein of claim 16, and the therapeutic cargo of claim 15.
Appel et al. teach peptide, protein, and DNA based vaccines may be used to induce immunity to various diseases or conditions; to detect and destroy virus-infected cells ([0111]) which meets the injectable hydrogel network being configured for use in infectious disease vaccine species of instant claim 18.
Conclusion
Claims 1-2 and 5-18 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571) 270-5896. The examiner can normally be reached 0830-1630. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool.
To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Karen A Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
Prosecution Insights