DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. The applicant's submission filed on 22 April 2026, has been entered.
Status of the Claims
Amendments to the Claims and Arguments/Remarks filed 22 April 2026, in response to the Office Correspondence dated 23 December 2025, are acknowledged.
The listing of Claims filed 22 April 2026, have been examined. Claims 1-9, 11-25, and 27-42 are pending. Claims 10, 26, and 43 are canceled, claim 1 is amended and no new claims have been added.
Response to Amendment
Pending claims 2-9, 11-14, 17-19, 40-42 have been previously presented or amended and claim 1 is currently amended. While the applicant has amended claim 1 to add structural and functional limitations, the claims remain rejected under 35 U.S.C. § 103 and new grounds of rejection are entered where appropriate. New grounds of objection and rejection under 35 U.S.C. § 112(b) have been entered for the claims as set forth below.
Claim Objections
Claims 12, 13, 18, 25, 27-30, and 36-38 are objected to because of the following informalities:
Claim 12 and 13 are objected to for the use of “(M)”. Claim 12 defines uses unnecessary repetition by defining M twice. Claim 13 uses M, which is defined in the claim in which it depends (claim 12), but subsequently defines it later in the claim after it has already been used. For consistency and clarity, “molecular weight (M)” just be defined at the first introduction and does not need to be repeatedly redefined. Once defined, “M” can be consistently used in place of the need for “molecular weight” (e.g., claim 12: “The multi-matrix controlled release system according to claim 11, wherein the hyaluronic acid salt is a low molecular weight (M), where M ≤0.75-106 Da, or the hyaluronic acid salt is a high M, where M ≤2.2-106 Da, or a mixture thereof.” and claim 13: “The multi-matrix controlled release system according to claim 12 wherein the hyaluronic acid salt is of low M, where 0.5-106 Da≤ M ≤0.75-106 Da or the hyaluronic acid salt of high M, where 1.9.106 ≤ M ≤ 2.2-106 Da, or a mixture thereof.”). Claims 27 and 28 also contain the same issue.
Claims 18, 25, 27-30, and 36-38 are objected to for missing the article before “Method according to claim…”, which should be “The method according to claim…”.
Claim 25 is also objected to for grammar in “when pH reached after the crosslinking step is acidic”, which is missing a “the”.
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 Applicant regards as his invention.
Claims 1-9, 11-25, and 27-42 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, regards as the invention.
Claim 1 is rejected as indefinite for the lack of antecedent basis for “the compositions”. The claim is directed to “a multimatrix controlled release system”, not “compositions”. The applicant is advised to amend the claim to “wherein the pH of the system…” or introduce “composition” earlier.
Claim 1 also recites the phrase “vehiculized through non-ionic surfactants”, which is not a standardized term in the art and is not defined in the specification with reasonable certainty. The specification does not provide objective structural or functional criteria for what constitutes “vehiculized” as distinct from “solubilized,” “encapsulated,” or “dispersed”.
The phrase “colloidal particles of the non-ionic surfactant are embedded within the cross-linked polymer net” is also indefinite because the specification fails to provide a standard for determining when a particle is “embedded” versus merely dispersed, suspended, or entrapped. The term “embedded” implies a degree of physical integration that is not objectively defined. The specification fails to provide objective structural or functional criteria for determining when a particle is “embedded” versus simply dispersed or suspended. The applicant states that the surfactant “colloidal particles are distributed, forming a multimatrix system”, but “distributed” and “embedded” are not synonymous. Without a clear standard, the scope of the claims is unclear (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 901 (2014), wherein a claim is indefinite if it fails to inform those skilled in the art about the scope of the invention with reasonable certainty).
Further, structural ambiguity exists as to the limitation of “integrated, chemically cross-linked three-dimensional structure” in claim 1. It is unclear whether surfactant participates in crosslinking, or are merely physically entrapped. The specification suggests physical encapsulation, not chemical integration but is not explicit, rendering the metes and bounds unclear.
In addition, claim 1 recites a measurement limitation that is unclear as, “retains at least 5% … after 24 hours”, in which there is no defined initial loading basis, no defined conditions (e.g., one of ordinary skill would not know with reasonable certainty the pH, molarity, or ionic strength of the buffer, all of which can dramatically affect release kinetics), no defined temperature or agitation and is only partially supported in two examples, wherein phosphate buffer mentioned but not fully standardized. The specification does not identify a standard protocol for this measurement.
Dependent claims 2-9, 11-25, and 27-42 are included in this rejection because they do not cure the defect noted above.
Claim 3 is rejected as indefinite for the lack of antecedent basis for “multimatrix controlled ethylene release system”, which introduces a different invention of ethylene. The antecedent subject matter should be phytocannabinoids rather than ethylene. As written, the claim is nonsensical and does not inform a skilled artisan of the scope of the invention. Dependent claims 4-7 are included in this rejection because they do not cure the defect noted above.
Claims 12 and 13 are rejected as indefinite for unclear antecedent basis of “…or a hyaluronic acid salt is a high…”, wherein the preceding alternative is “the hyaluronic acid salt” and the introduction of “a hyaluronic acid salt” suggests a new hyaluronic acid, separate from that of the previously introduced as “a hyaluronic acid, or a derivative thereof”, and in addition to it rendering the scope of the claim unclear. Similarly, claims 27 and 28 both refer to “a hyaluronic acid salt” and depend from claim 15 which has an antecedent basis of “hyaluronic acid, or a derivative thereof”, which is already specified in the claim from which it depends as the polymer (claim 1), thus it is unclear if the “a hyaluronic acid salt” is in addition to the previously specified “hyaluronic acid, or a derivative thereof” of claim 15 which is already defined as the polymer in claim 1. The claims would be clearer if they explicitly specify, “wherein the hyaluronic acid, or a derivative thereof, is a hyaluronic acid salt having a low molecular weight (M)…or a high M…, or a mixture thereof.”. Appropriate correction is required to clarify the antecedent basis of “hyaluronic acid salt” in the claims. Dependent claims 29 and 30 are included in this rejection because they do not cure the defect noted above.
Claim 15 is rejected as indefinite for the use of “a proper solvent”, wherein a “proper solvent” introduces ambiguity as to what qualifies as a proper solvent. “Proper solvent” is purely subjective and fails to inform the scope with reasonable certainty. The applicant is advised to amend the claim to specify appropriate solvents or amend the specification to explicitly define the scope of what is considered a “proper solvent”. Dependent claims 16-21 are included in this rejection because they do not cure the defect noted above.
Claim 23 is rejected as indefinite for referring to step i) for phytocannabinoids dissolution, which is inconsistent with claim 22, from which it depends wherein phytocannabinoids appear in step ii. Appropriate correction is required. Dependent claim 24 is included in this rejection because they do not cure the defect noted above.
Claim 30 is rejected as indefinite for reciting “preferably in a concentration between 0.5% and 2.5% (w/w) and most preferably in a concentration between 0.75 and 1.5% (w/w).” The terms “preferably” and “most preferably” do not define the scope of the invention with particularity. It is unclear whether the claimed method requires the recited concentrations or merely prefers them (see Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008)). The applicant is advised to consider removing the preferably and most preferably concentrations in the claim.
Claim 39 is rejected as indefinite for referring to a “system of cannabinoids formulation according to claim 1”, being inconsistent with claim 1, from which it depends which uses phytocannabinoids, resulting in potential scope ambiguity. It is unclear whether the terms are intended to be synonymous or whether the scope differs. “Cannabinoids” is broader than “phytocannabinoids” and may include synthetic cannabinoids not supported by the specification. The applicant is advised to amend the claim by replacing cannabinoids with phytocannabinoids, to establish consistent antecedent basis. Dependent claims 40-42 are included in this rejection because they do not cure the defect noted above.
Claim 42 is rejected as indefinite with respect to the recited effects “promoting skin relaxation, calming and moisturization, and improving the well-being of the human body.” The specification does not provide any data, clinical results, or even qualitative description demonstrating that the claimed composition achieves these specific physiological or psychological effects. No assays, protocols, or endpoints are disclosed for measuring “relaxation,” “calming,” or “well-being.” Accordingly, the specification does not reasonably convey to a skilled artisan what is encompassed within the scope of the claim.
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 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, 11-22, 25, 32-36, and 39-41 are rejected under 35 U.S.C. § 103 as being unpatentable over Gedo (US-20200121616-A1; publication date 23 April 2020), in view of Wilkhu (WO2019135076A1; publication date 11 July 2019), and in further view of Babo (Babo PS, Reis RL, Gomes ME. Production and characterization of hyaluronic acid microparticles for the controlled delivery of growth factors using a spray/dehydration method. Journal of Biomaterials Applications. 2016;31(5):693-707).
Gedo teaches compositions comprising a combination of cannabidiol (CBD) or a derivative thereof including phytocannabinoids (CBD, cannabis extract, ¶[0032]; cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), or any combination thereof. In one embodiment, a composition as described herein further comprises at least two compounds selected from the group comprising: cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), or any combination thereof, ¶[0075]), hyaluronic acid or derivative or a salt thereof (claim 1, ¶[0035], ¶[0037]-[0043]) that maybe cross-linked (¶[0039]; explicitly teaches crosslinking HA via multiple methods), non-ionic surfactants including poloxamers and Tweens as formulation components (¶[0102]; Tween 20, Tween 80, Pluronic F68 and polymer coatings such as poloxamers or poloxamines), a pH range 6-8 (¶[0072]; physiological pH 7.3-7.45 is within 6-8), weight ratios of phytocannabinoid/polymer of 10-100 mg/ml CBD (¶[0063]) and 1-5 mg/ml HA (¶[0065]) yielding a ratio range 2:1 to 100:1 which overlaps with a 50:1 to 1:50 range, and methods of using the pharmaceutical compositions for treating inflammatory joint diseases (¶[0123], intra-articular injection into inflamed joint; ¶[0148], treat inflammation to alleviate joint pain) and soft tissue repair/augmentation (¶[0148] to rebuild connective tissue; keratins are structural proteins in synovial membrane, inherently involved).
Gedo explicitly teaches that hyaluronic acid “can be crosslinked” (Gedo, ¶[0039]) and discloses multiple crosslinking methods, including formaldehyde, divinylsulfone, glutaraldehyde, and attachment of thiol groups or methacrylates. Gedo teaches that the composition is formed by “suspending the mixture [of CBD, phospholipid, and cholesterol] in a solution of hyaluronic acid” (¶[0019]). When the HA is crosslinked as taught, the resulting structure inherently embeds surfactant components within the crosslinked network.
One of ordinary skill would understand that crosslinking a polymer solution containing dispersed colloidal particles results in an embedded structure. The instant claimed embedding is not structurally distinct from what Gedo inherently produces when its crosslinking teaching is followed. The claimed “integrated” structure is thus neither structurally nor functionally distinct from what Gedo would produce when its crosslinking teaching is applied. Thus, the integrated three-dimensional structure is a natural and inherent consequence of crosslinking HA in the presence of dispersed surfactant and cannabinoid. The instant claim does not require that the surfactant be chemically crosslinked to the polymer, only that the overall structure is chemically crosslinked and Gedo’s crosslinked HA satisfies this limitation.
In addition, Babo teaches crosslinking hyaluronic acid in the presence of dispersed phases resulting in microparticle entrapment within a crosslinked network for controlled release. Thus, even if this was not inherent in the not inherent Gedo’s crosslinking teaching when applied, the “embedded colloidal particles” limitation is explicitly suggested by Babo and thus would be an obvious modification.
With respect to a release profile that retains at least 5% after 24 hours in phosphate buffer, Gedo teaches controlled release systems. One of ordinary skill would routinely measure release in phosphate buffer (a standard medium). It is well-established that increasing crosslinking density reduces release rate and increases retention. One of ordinary skill would routinely adjust crosslinking conditions (e.g., carbodiimide concentration, reaction time) to achieve the claimed retention of at least 5% after 24 hours. Optimizing crosslinking density to achieve a desired retention is a matter of routine experimentation (see In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). The claimed retention of at least 5% is a minimal, low threshold that any crosslinked HA system would meet unless deliberately formulated for complete release. The newly added limitations to instant claim 1 are expected from the combination of Gedo, Wilkhu, and Babo.
With respect to the phytocannabinoid/surfactant weight ratio (1:30 to 1:1), Gedo teaches phospholipid/CBD ratios >1:10 (¶[0067]). Substituting a non-ionic surfactant for the amphoteric phospholipid and adjusting the ratio within an order of magnitude is a predictable variation using routine experimentation. The claimed range is broad (1:30 to 1:1) and overlaps with what one would naturally optimize for solubility and release.
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to formulate a crosslinked HA system containing phytocannabinoids and non-ionic surfactants with a reasonable expectation of success because Gedo already teaches each component individually, crosslinking HA is a well-established technique, non-ionic surfactants are known to be compatible with HA and cannabinoids, and the claimed release profile is minimal and routine to achieve.
Gedo does not teach the use of poly (ethylene glycol)-block-poly (propylene glycol)-block-poly(ethyleneglycol) derivative non-ionic surfactants.
Wilkhu teaches PEG-PPG-PEG block copolymer (poloxamer) as non-ionic surfactant (page 12, lines 6-7 as poloxamers generally) and an explicit poloxamer formula with integers a, b with blends of two poloxamers having specific a, b values including poloxamer 188 (a=80 and b=27; page 12, lines 16 and 17) and poloxamer 338 (a=141 and b=44; page 12, lines 23-24) and poloxamer 124 (a=12 and b=20; page 12, lines 13 and 14) and poloxamer 237 (a=64 and b=37; page 12, line 23) but not a=64 and b=34. Wilkhu does not explicitly teach the two poloxamer derivatives together, however, page 12, lines 19-21 discloses that the formulation may comprise two poloxamers, preferred as poloxamer 124 and poloxamer 188.
The difference of b=34 vs. b=37 is minor and it would be obvious to modify the block lengths by routine experimentation to achieve the desired result, given the invention is aimed at modifying block lengths to achieve desired controlled release profiles. Alternatively, one skilled in the art could blend poloxamer 237 (a=64, b=37) + poloxamer 181 (a=3, b=30) and adjust the ratios to approximate properties and meet the instant claim limitation through routine experimentation.
Wilkhu teaches “The pharmaceutical formulation comprises at least one cannabinoid; at least one poloxamer; and a solvent, wherein the solvent is defined according to formula (I)
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wherein R1 and R2 are independently selected from hydrogen, C(0)CH3, OH, C(0)CH3, CH2OH and C(0)0CH2CH3; R3 is independently selected from CH3, CH2OH, OH, CH20C(0)CH3 and CH2C(0)CH2CH3; and R4 is independently selected from hydrogen and C(0)0CH2CH3.” (page 4, lines 26-31 and page 5, lines 1-2), wherein “The solvent may be selected from the group consisting of diacetin, propylene glycol, triacetin, monoacetin, propylene glycol diacetate, triethyl citrate and mixtures thereof.” (page 9, lines 10-12).
Gedo provides the overall framework of a crosslinkable HA-based phytocannabinoid system. Wilkhu provides specific structural definitions for poloxamer non-ionic surfactants and solvents that Gedo lacks. Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine these references because both references are directed to controlled-release cannabinoid formulations. Gedo focuses on injectable HA-based systems for joint therapy and Wilkhu focuses on poloxamer-based systems for modified cannabinoid release. The shared goal of improving solubility and controlled release provides a direct motivation to incorporate Wilkhu’s poloxamer technology into Gedo’s HA matrix (see In re Vaeck, 947 F.2d 488, 493 (Fed. Cir. 1991), wherein references directed to similar problems or purposes suggest motivation to combine).
Gedo already lists poloxamers as acceptable excipients (¶[0102]). Wilkhu merely provides the specific parameters (a, b integers) that characterize those poloxamers. Substituting a generic teaching with a specific embodiment is prima facie obvious (see In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012)). Wilkhu teaches that modifying a and b integers alters release profiles (page 12, lines 22-25). One of ordinary skill would routinely vary these integers within the disclosed ranges (a=10–150, b=15–65) to achieve desired release kinetics. The specific a, b pairs in claims 6-7 are either explicitly taught (a=80, b=27; a=141, b=44; a=12, b=20) or are minor variants (b=34 vs. b=37) that are obvious to try (see In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985), wherein optimization of variables in a known process is obvious). One of ordinary skill would have had a reasonable expectation of success because poloxamers are known to be compatible with both hydrophobic drugs and hydrogel matrices, Wilkhu demonstrates that poloxamers effectively solubilize cannabinoids and Gedo demonstrates that HA accepts non-ionic surfactants. The combination is simply the substitution of one known surfactant class for another, with routine optimization of block lengths.
Gedo mentions crosslinking of HA (¶[0039]) but does not explicitly teach carbodiimide/dihydrazide chemistry. Babo fills this gap. Babo teaches carbodiimide cross-linking of hyaluronic acid with ADH using carbodiimide-based chemistry and dihydrazide derivative (ADH) present (page 2, left column, paragraph 2). Babo also teaches pH adjustment after crosslinking (page 2, right column, paragraph 1; “pH of the HA/ADH solution was set to 4.75 with 3M HCl”).
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to use Babo’s carbodiimide/dihydrazide crosslinking method in the invention of Gedo because Gedo already contemplates crosslinking HA but does not specify a method Babo provides a routine, well-known method (FDA-approved method for crosslinking HA in clinical hydrogels/dermal fillers). The combination is merely implementing a known process in the framework of Gedo’s composition (see KSR, 550 U.S. at 417, wherein if a technique has been used to improve one device, and a person of ordinary skill would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill).
One would have a reasonable expectation of success in doing so because Babo demonstrates successful crosslinking of HA with carbodiimide/ADH. Applying that same chemistry to Gedo’s HA-cannabinoid-surfactant mixture would be expected to work because the chemistry is specific to HA’s carboxylic acid groups. The presence of cannabinoids and surfactants does not interfere with carbodiimide chemistry (neither contains reactive groups that compete). Routine experimentation would optimize conditions (e.g., EDC concentration, reaction time).
Claims 1, 8, 9, and 22-24 are rejected under 35 U.S.C. § 103 as being unpatentable over Gedo (US20200121616A1; publication date 23 April 2020) in view of Wilkhu (WO2019135076A1; publication date 11 July 2019), Babo (Babo PS, Reis RL, Gomes ME. Production and characterization of hyaluronic acid microparticles for the controlled delivery of growth factors using a spray/dehydration method. Journal of Biomaterials Applications. 2016;31(5):693-707), Naheed (US9827322B2; publication date: 28 October 2017), and Friedman (US20190298683A1; publication date: 03 October 2019).
Claim 1 and 8 are rejected based on rejecting claim 9, in which it depends, and claim 1 based on rejecting claims 22-24, in which it depends.
Gedo, Wilkhu, and Babo disclose the limitations as described above. Gedo and Wilkhu do not explicitly disclose wherein the non-ionic surfactant is a combination of glyceryl citrate/lactate/linoleate/oleate and polyglyceryl-2 oleate.
Friedman teaches glyceryl linoleate (corn oil PEG-6 esters), glyceryl monooleate, glyceryl dioleate, polyglyceryl oleate, and polyglyceryl-2 dioleate (¶[0090] and ¶[0091]) and Naheed teaches esters including citrates (glyceryl citrate) as plasticizing agents (column 53, lines 52-55). Gedo teaches the use of cannabis sativa extract (¶[0032]; cannabis extract includes sativa) and mixing HA solution with the surfactant (phospholipid ) and cannabinoid (CBD) solution (¶[0019] (mixing CBD/phospholipid with HA solution). Wilkhu teaches combining the poloxamer, cannabinoid and solvent and Friedman teaches the specific surfactants.
The exact combination of glyceryl citrate/lactate/linoleate/oleate with polyglyceryl-2 oleate is not explicitly disclosed in a single reference, however, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine Gedo’s HA-cannabinoid framework with Wilkhu’s poloxamer technology, Naheed’s teaching of citrates as plasticizers/solubilizers for cannabis-HA compositions, and Friedman’s explicit teaching of glyceryl and polyglyceryl oleate esters for cannabinoid emulsification because the combination is a simple substitution of one non-ionic surfactant combination for another. All references recognize that non-ionic surfactants are interchangeable for solubilizing cannabinoids.
The specific surfactant combination in instant claim 9 is merely one of many known in the art (Friedman, ¶[0090] lists “mixtures thereof”). Selecting this specific pair is an obvious without unexpected results and one would have a reasonable expectation of success in doing so as all components are pharmaceutically acceptable, commercially available, and known to be compatible.
Claims 1, 15, 37 and 38 are rejected under 35 U.S.C. § 103 as being unpatentable over Gedo (US20200121616A1; publication date 23 April 2020) in view of Wilkhu (WO2019135076A1; publication date 11 July 2019), Babo (Babo PS, Reis RL, Gomes ME. Production and characterization of hyaluronic acid microparticles for the controlled delivery of growth factors using a spray/dehydration method. Journal of Biomaterials Applications. 2016;31(5):693-707), and Shimojo (Shimojo, Andrea Arruda Martins. “Sterilization of Auto-Crosslinked Hyaluronic Acid Scaffolds Structured in Microparticles and Sponges.” Bio-medical materials and engineering. 26.3–4 (2015): 183–191).
Claims 1 and 15 is rejected based on rejecting claim 37, in which it depends. Gedo, Wilkhu and Babo disclose the limitations as described above. Neither Gedo nor Wilkhu teaches sterilization of the final composition. Shimojo fills this gap.
Shimojo teaches steam sterilization treatment (autoclave) of crosslinked HA scaffolds as, “The treatment was achieved by wet heating at 126°C under a vapor pressure of 1.5 kgf/cm2 for 1, 2.5, 5, 10 and 15 min in an autoclave.” (page 3, paragraph 4).
Thus, would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to add the sterilization step. Sterilization is a routine, essential step for clinical-grade biomaterials, wherein a routine sterilization step cannot transform an otherwise obvious composition into a patentable invention. One of ordinary skill would recognize that a pharmaceutical composition intended for injection, as taught by Gedo (¶[0123]) must be sterilized. Autoclaving is a standard method for heat-stable hydrogels.
Shimojo demonstrates its applicability to crosslinked HA. Thus, adding a sterilization step to Gedo’s process is obvious. One would have a reasonable expectation of success in adding the autoclave sterilization of crosslinked HA scaffolds because it is taught by Shimojo to be successful and one would reasonably expect that the Gedo/Wilkhu composition, being similarly crosslinked HA, would survive autoclaving without degradation, or that routine adjustments (e.g., reducing time/temperature) would achieve sterilization.
Claims 1, 39, and 42 are rejected under 35 U.S.C. § 103 as being unpatentable over Gedo (US20200121616A1; publication date 23 April 2020) in view of Wilkhu (WO2019135076A1; publication date 11 July 2019), Babo (Babo PS, Reis RL, Gomes ME. Production and characterization of hyaluronic acid microparticles for the controlled delivery of growth factors using a spray/dehydration method. Journal of Biomaterials Applications. 2016;31(5):693-707), and Kleidon (WO2016094810A2; publication date 11 December 2015).
Claims 1 and 39 are rejected based on rejecting claim 42, in which it depends. Gedo, Wilkhu and Babo disclose the limitations as described above, however, neither Gedo nor Wilkhu explicitly teach cosmetic or nutraceutical use for skin relaxation, calming, and moisturization.
Kleidon teaches cannabinoid compositions wherein cannabidiol extract compounds from plant sources relax, calm and moisturize skin as, “Phytol can be used to relax a subject, such as by inhibiting degradation of GABA, as an anxiolytic, to resist menadione-induced oxidative stress, and as an antimicrobial” (¶[0079]), “Sabinene can be used…relieve skin conditions.” (¶[0081]), “Camphor can be used to improve skin healing (e.g., reconstructed human epidermis), as a local anesthetic, a muscle relaxant, an antipathogenic, and an antimicrobial agent.” (¶[0082]) and wherein, The compositions of the present disclosure can be provided as cosmetics or personal care products, such as…lotions, massage oils masks, makeup, moisturizers…” (¶[00110]).
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine the teaching of Kleidon that cannabinoid-containing compositions provide the instant claimed dermatological and psychological benefits for use with the Gedo/Wilkhu delivery system, which effectively delivers cannabinoids, for these known cosmetic purposes. This is a simple application of a known composition to a known use (see In re Dillon, 919 F.2d 688, 692-93 (Fed. Cir. 1990) (en banc), wherein knowledge that a composition has a particular property motivates its use for that property). Because Kleidon demonstrates that cannabinoids themselves provide the claimed benefits, and Gedo/Wilkhu provides a biocompatible delivery system for cannabinoids, one would reasonably expect that topical application of the Gedo/Wilkhu composition would similarly provide those benefits.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 22 April 2026, have been fully considered. While the applicant has amended claim 1 to add structural and functional limitations, the claims remain rejected under 35 U.S.C. § 103 and new grounds of rejection are entered where appropriate.
Independent claim 1 has been amended to recite an integrated, chemically cross-linked three-dimensional structure, colloidal particles of non-ionic surfactant embedded within a cross-linked polymer network, and a functional limitation requiring ≥5% phytocannabinoid retention after 24 hours. These limitations have been considered but do not overcome the prior art for the reasons below.
The applicant argues that Gedo discloses only a simple physical mixture of pre-formed liposomes suspended in HA, whereas the claims require an integrated chemically cross-linked structure with embedded colloidal particles. This argument is not persuasive. Gedo explicitly teaches crosslinkable hyaluronic acid networks (¶[0039]) and discloses multiple crosslinking methods, including formaldehyde, divinylsulfone, glutaraldehyde, and attachment of thiol groups or methacrylates. The fact that Gedo’s example uses uncrosslinked HA does not negate its affirmative teaching of crosslinked HA compositions. Gedo also teaches inclusion of surfactants, including non-ionic surfactants such as poloxamers (¶[0102]), and formation of aqueous compositions containing dispersed phases (¶[0073] and ¶[0074]). Gedo teaches that the composition is formed by “suspending the mixture [of CBD, phospholipid, and cholesterol] in a solution of hyaluronic acid” (¶[0019]).
A person of ordinary skill in the art, applying routine formulation principles, would recognize that incorporating surfactant-based colloidal systems (micelles or vesicles) prior to or during crosslinking inherently results in physical entrapment/embedding within the polymer network. Such embedding is a natural consequence of gelation in the presence of dispersed colloids, not a patentably distinct structural feature. When the HA is crosslinked as taught by Gedo, the resulting structure inherently embeds surfactant components within the crosslinked network. The claimed “integrated structure” therefore represents an inherent result of known formulation steps, rather than a structural distinction requiring separate teaching.
The applicant has not demonstrated, nor do the claims require, that crosslinking occurs in situ in the presence of surfactant micelles. The claim does not require that the surfactant be chemically crosslinked to the polymer, only that the overall structure is chemically crosslinked and Gedo’s crosslinked HA satisfies this limitation. The claimed “integrated” structure is thus neither structurally nor functionally distinct from what would be produces when Gedo’s crosslinking teaching is applied (see In re Best, 562 F.2d 1252 (CCPA 1977), wherein a claimed structure is inherently produced by prior art process).
In addition, Babo teaches crosslinking hyaluronic acid in the presence of dispersed phases resulting in microparticle entrapment within a crosslinked network for controlled release, thus the “embedded colloidal particles” limitation is explicitly suggested and thus would be an obvious modification.
The applicant asserts that substitution of phospholipids with non-ionic surfactants (e.g., poloxamers) is non-obvious due to different self-assembly mechanisms and that one of skill would not replace amphoteric phospholipids with non-ionic poloxamers because they form bilayer vesicles versus micelles. This argument is not persuasive.
Gedo expressly teaches the use of non-ionic surfactants (poloxamers, PEG-based systems) as interchangeable excipients (¶[0102]). Gedo does not criticize, discredit, or teach away from non-ionic surfactants. The preference for phospholipids in examples does not constitute a teaching away (see In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994), wherein a reference may teach away when it suggests that the line of development flowing from the reference’s disclosure is unlikely to be productive of the result sought by the applicant). Here, Gedo’s express listing of non-ionic surfactants as useful components does the opposite.
Moreover, both phospholipids and poloxamers are well-known surfactant classes for formulating hydrophobic drugs, routinely selected based on formulation optimization criteria. Wilkhu explicitly teaches poloxamer-based cannabinoid delivery systems with controlled release. Substituting one known surfactant for another to achieve predictable solubilization and controlled release is obvious to try with a reasonable expectation of success (see In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980), wherein substitution of one known surfactant for another is prima facie obvious where both are known to be effective for the same purpose). The applicant’s argument focuses on mechanistic differences, whereas the legal inquiry is predictability of functional outcome, which is clearly established.
The applicant has amended claim 1 to require retention of at least 5% of the phytocannabinoid after 24 hours and as such, the applicant asserts this is unexpected (based on Example 12) and a direct consequence of the unique integrated structure. This argument is not persuasive for multiple independent reasons.
First, a release profile showing 95% release after 24 hours (i.e., 5% retention) is not unexpected. Gedo teaches a controlled release system. Controlled release systems routinely exhibit partial retention at 24 hours depending on polymer crosslinking density, surfactant selection, and drug loading. A retention of ≥5% after 24 hours corresponds to 95% release within 24 hours, which is consistent with known burst-release profiles of hydrogel/micellar systems. No evidence has been provided showing that the claimed system performs differently from prior art compositions with crosslinked HA and non-ionic surfactant under identical conditions and produces a substantially different release profile. No side-by-side comparison with Gedo compositions, or Gedo and Wilkhu combinations has been provided. Thus, no nexus has been established between the claimed structure and the alleged result.
Second, the claimed retention value (≥5%) is exceptionally low. A system that retains only 5% payload has released 95%, there is no unexpected synergy or criticality demonstrated by such a minimal retention threshold (see In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997), wherein unexpected results must be sufficiently greater than expected to overcome prima facie obviousness).
Third, the applicant has not provided any evidence that the claimed release profile is structurally dependent on the integrated multi-matrix feature rather than routinely achievable by crosslinking density and surfactant selection. Release kinetics are a result-effective variable dependent on crosslink density, surfactant concentration, polymer molecular weight, wherein optimization of such variables is routine (see In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003)). Without comparative data against a prior art formulation (e.g., Gedo with crosslinked HA and a poloxamer), the applicant cannot establish that the claimed structure produces unexpected results.
The applicant contends there is no motivation to replace liposomes with poloxamers and combine Wilkhu with Gedo. This argument is not persuasive. Both references are directed to cannabinoid solubilization, and controlled/modified release systems. Wilkhu explicitly teaches use of dual poloxamer systems to modulate release kinetics. Gedo teaches HA-based delivery systems for cannabinoids, including crosslinked matrices. A person of ordinary skill in the art would be motivated to incorporate Wilkhu’s poloxamer system into Gedo’s HA matrix to improve solubility, stability, and release kinetics. This constitutes a classic combination of known elements for predictable results under KSR v. Teleflex, 550 U.S. 398 (2007).
The applicant emphasizes embedding of colloidal particles within the polymer network. This argument is not persuasive. When micelles from poloxamers are present in solution, and crosslinking of HA occurs, the resulting structure will inherently trap and embed those micelles within the polymer mesh. This is a well-understood phenomenon in hydrogel drug delivery systems, and does not require explicit teaching in the prior art. Accordingly, the limitation is inherent.
The applicant notes that a counterpart European application has been allowed. The applicant is reminded that foreign prosecution outcomes are has no binding effect on USPTO examination (see In re Sneed, 710 F.2d 1544, 1550 (Fed. Cir. 1983), wherein the USPTO is not bound by a foreign patent office’s determination of patentability, and MPEP § 2141. The legal standards for obviousness differ between the USPTO and the EPO.
In summary, the applicant’s amendment and remarks have been fully considered but do not overcome the prior art. To rebut a prima facie case of obviousness, the applicant must show that the claimed invention as a whole would not have been obvious (see In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992)). The applicant’s arguments focus on differences between Gedo and the claimed invention, but fail to address that Gedo in combination with Wilkhu, Babo, Shimojo, Naheed, Friedman, and Kleidon teaches every limitation. The fact that Gedo does not explicitly disclose a chemically integrated three-dimensional structure with embedded poloxamer micelles is irrelevant where the combination of references teaches these features and the artisan would have been motivated to combine them (see KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), wherein a patent composed of several elements that are simply a combination of prior art elements does not become patentable simply because it includes a high number of elements).
To overcome the prior art rejections, it would be necessary to provide comparative experimental evidence demonstrating unexpected results versus the closest prior art, and amend the claims to recite structural limitations that clearly distinguish over inherent gel entrapment phenomena. In addition, the applicant would need to overcome §112(b) rejections outlined for the claims above.
Conclusion
No claims are allowed.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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