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 .
Claim Status
The claim set and Applicant’s remarks filed June 25, 2026 have been entered.
Claims 9-11 are canceled.
Thus, claims 1-8 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on March 26, 2026:
(I) The rejection of claims 1-2, 4-6 and 8 under 35 U.S.C. 102(a)(1); and
(II) The rejection of claims 1-2 and 4-8 on the ground of nonstatutory double patenting are each withdrawn in view of Applicant’s amendment to claim 1.
Response to Arguments
(I) The rejection of claims 1-8 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is maintained as the Examiner notes the rejection stated claims 1-8 were enabled for treating atopic dermatitis, psoriasis, allergic dermatitis, seborrheic dermatitis, and contact dermatitis with the hyaluronic acid conjugates recited in claim 1; and not for preventing as claimed.
The Examiner notes preventing inflammatory skin diseases is still a recited limitation within line 1 in each of claims 1-8.
The Examiner further notes the 112(a)-enablement rejection has been maintained and modified in view of the amendments to claims 1-8.
(II) The rejection of claim 7 is maintained in view of the new 103 rejection rejecting at least claim 1 as discussed below.
Applicant argues:
(A) Kim does not teach the required lithocholic acid, cholesterol or a combination thereof as the hydrophobic substance, see Applicant’s remarks, pg. 7, paragraph 5.
(B) Yang does not teach or suggest treating the specific inflammatory skin diseases now claimed by administering a hyaluronic acid conjugate comprising lithocholic acid and/cholesterol, see Applicant’s remarks, pg. 7, paragraph 6.
(C) Even if Kim and Yang were combined, the combination would not directly lead to the amended claims, see Applicant’s remarks, pg. 7, paragraph 6.
With respect to Applicant’s arguments (A)-(C), the Examiner notes the addition of the Shi reference teaches use of treating psoriasis by administering lithocholic acid; and since Kim already teaches treating inflammatory diseases by administering hyaluronic acid conjugates comprising 5β-cholanic acid, and methods of preparing such conjugates, it would have been prima facie obvious to one of ordinary skill in the art to have replaced the 5β-cholanic acid taught by Kim for lithocholic acid as taught by Shi in order to treat a different inflammatory disease, e.g. psoriasis, as discussed in greater detail below.
Thus, Applicant’s arguments (A)-(C) have been fully considered but are not found persuasive.
New Claim Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on June 25, 2026, where the limitations in pending claims 1-8 as amended now have been changed.
Therefore, rejections from the previous Office Action, dated March 26, 2026, have been modified and are listed below.
35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating atopic dermatitis, psoriasis, allergic dermatitis, seborrheic dermatitis, and contact dermatitis with a hyaluronic acid conjugate consisting of hyaluronic acid and either lithocholic acid, cholesterol or a combination thereof as the hydrophobic substance, does not reasonably provide enablement for preventing said diseases listed above. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a result, substantiation of utility and its scope is required when utility is
speculative, sufficiently unusual or not provided, and enablement must be
commensurate with the scope of the claim language. As MPEP § 2164.08 states, “The
Federal Circuit has repeatedly held that "the specification must teach those skilled in the
art how to make and use the full scope of the claimed invention without ‘undue
experimentation’." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir.
1993).”
As stated in MPEP § 2164.01(a), “There are many factors to be considered when
determining whether there is sufficient evidence to support a determination that a
disclosure does not satisfy the enablement requirement and whether any necessary
experimentation is “undue”.”
The applicant’s attention is drawn to In re Wands, 858 F.2d 731, 737, 8 USPQ2d
1400, 1404 (Fed. Cir. 1988), where the court set forth eight factors to be considered in
determining whether a disclosure meets the enablement requirement of 35 U.S.C.
112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. They are: (1) The nature of the
invention; (2) The state of the prior art; (3) The level of skill in the art; (4) The
predictability or lack thereof in the art; (5) The breadth of the claims; (6) The amount of
direction or guidance present; (7) The presence or absence of working examples; and
(8) The quantity of experimentation needed.
It is noted that all of the Wands factors have been considered with regard to the
instant claims, with the most relevant factors discussed below.
The nature of the invention: The claimed invention is drawn to treating or preventing atopic dermatitis, psoriasis, allergic dermatitis, seborrheic dermatitis, and contact dermatitis in a subject comprising administering a hyaluronic acid conjugate composed of hyaluronic acid and either lithocholic acid, cholesterol or a combination thereof as the hydrophobic substance as an active ingredient as required in claims 1-8.
Therefore, to be enabled for the full scope of treatment or prevention of said skin disease, one skilled in the art must reasonably be able to ascertain which agents are effective, obtain said agents, and successfully use said agents for treating or preventing said skin disease.
The state of the prior art: The state of the art does not recognize preventing atopic dermatitis, psoriasis, allergic dermatitis, seborrheic dermatitis, and contact dermatitis with a hyaluronic acid conjugate composed of hyaluronic acid and either lithocholic acid, cholesterol or a combination thereof as the hydrophobic substance. Attention is drawn to Lee et al. (Published 14 November 2022, ACS Nano, Vol. 16, Issue 12, pp. 20057-20074, IDS filed 11/19/2024), Lee teaches hyaluronic acid nanoparticles (HA-NPs) as a topical agent for treating psoriasis, see pg. 20057, title.
Lee teaches HA-NPs as topical therapeutics for treating psoriasis using in vivo skin penetration studies and psoriasis animal models, see pg. 20057, abstract.
Lee teaches using amphiphilic HA-LCA conjugates, where hydrophilic 60 kDa free hyaluronic acids (HAs) were chemically conjugated with hydrophobic lithocholic acid (LCA, Figure S1), see pg. 20059, left column, results and discussion, efficacy against psoriasis-like skin dermatitis, paragraph 1.
Lee teaches the specific HA-LCA conjugate known as HALN-3 (also referred to as HALN) was administered via the subcutaneous route in psoriasis-like skin dermatitis. Lee concludes that an empty self-assembled HALN itself is sufficient to protect animals against psoriasis-like skin dermatitis safely and effectively, see pg. 20059, right column, paragraph 2.
Lee teaches HALN subcutaneously administered into IMQ-inflamed mice normalized the levels of ceramide (Figure 5A), the major skin barrier lipid in the SC; claudin-1, the major component of tight junctions forming the epidermal barrier function; and antimicrobial peptide S100A9, see pg. 20061, right column, restoration of skin barrier function, paragraph 1.
Lee concluded HALN restored skin barrier functions, see pg. 20063, left column, paragraph 1.
The Examiner respectfully notes Lee does not teach or suggest the administered HA-LCA conjugates (HALN) can prevent psoriasis as recited by Applicant within each of claims 1-8.
The relative skill in the art: The relative skill of those in the art is high.
The predictability or lack thereof in the art: As discussed above, Lee teaches administering hyaluronic acid conjugates consisting of lithocholic acid and/or cholesterol as a topical agent in treating or preventing psoriasis as well as specific forms of dermatitis as recited in instant claim 1.
However, Lee does not demonstrate the hyaluronic acid conjugates consisting of lithocholic acid can prevent psoriasis let alone the other inflammatory skin diseases recited in claims 1-8 as written above.
As a result, at the time of the invention the use of hyaluronic acid conjugates as recited within claim 1 to prevent the recited inflammatory skin diseases was limited. Therefore, at the time of the invention the field of therapeutic use in preventing the recited skin diseases with the hyaluronic acid conjugates as recited within claim 1 was relatively underdeveloped and unpredictable.
The breadth of the claims: The claims are extremely board in that it encompasses both prevention and treatment of the recited inflammatory skin disasesin a subject using the instantly claimed method comprising administering a hyaluronic acid conjugate composed of hyaluronic acid and either lithocholic acid, cholesterol or a combination thereof as the hydrophobic substance as an active ingredient.
The amount of direction or guidance present: Applicants provide general guidance that the hyaluronic acid conjugates of the claimed invention are self-assembling; have excellent resistance to hyaluronidase and transdermal permeability; have excellent effects on the protection and recovery of skin barrier function; inhibit expression of cell proliferation-related factors and inflammatory cytokines; inhibit M1 macrophage polarization; and block TLR4 signaling which may be used as an agent for treating various skin diseases.
However, as discussed in the State of the Prior Art section above, Lee teaches administering hyaluronic acid conjugates consisting of lithocholic acid as a topical agent in treating psoriasis and not in preventing psoriasis.
Furthermore, Applicants do not provide any direction or guidance on the proposed mechanism of action used by the hyaluronic acid conjugates of claims 1-8 in preventing any of the recited inflammatory skin diseases of claim 1, which is particularly important in view of the Nature of Invention section as discussed above.
The presence or absence of working examples: Applicants provide experimental examples using specific hyaluronic acid conjugates to treat psoriasis within the specification.
Experimental Example 2 discloses psoriasis animal models were treated with hyaluronic acid conjugates HALN-1 to 3 injected subcutaneously at a dose of 20 mg/kg for 4 days, see specification, pg. 27, paragraph [00114].
The specification discloses Figs. 3 and 4 confirmed when HALN-1 to 3 were administered, erythema, scaling, and skin thickness were reduced compared to when PBS was administered. See pg. 28, paragraph [00118].
Experimental Example 5 discloses a concentration-dependent effect of transdermal administration of HALN-2 on treatment of psoriasis, see pg. 33, paragraphs [00143]-[00146] and Figs. 11-14.
Finally, Experimental Example 12 discloses treatment effects of psoriasis-induced mice with various types of hyaluronic acid conjugates containing lithocholic acid (HALN) or cholesterol (HACHN) at either a molecule weight of 10kDa or 60kDa, see pp. 48-49, paragraphs [00215]-[00222].
Experimental 12 discloses as shown in Figs. 25 to 26 where the hyaluronic acid conjugates comprise the different types of hydrophobic substances bound to hyaluronic acids reduced the PASI score, skin thickness, skin cell proliferation, and inflammatory response in the group to which each of the hyaluronic acid conjugates were applied, see pg. 50, paragraph [00228] and Figs. 25-26.
However, the Examiner respectfully notes the specification only provides data administering hyaluronic acid conjugates composed of lithocholic acid or cholesterol in treating psoriasis and does not provide any data demonstrating said conjugates can prevent psoriasis, which is consistent with the State of the Prior Art above.
Thus, the Examiner respectfully notes Applicant’s examples are not commensurate in scope with preventing any of the recited inflammatory skin diseases with a hyaluronic acid conjugate composed of hyaluronic acid and either lithocholic acid, cholesterol or a combination thereof.
Accordingly, the experimental examples discussed above do not support using the claimed hyaluronic acid conjugates of claim 1 in preventing any inflammatory skin disease recited in claim 1.
Note the lack of working examples is a critical factor to be considered, especially in a case involving the unpredictability of and underdeveloped art of HA-conjugates recited in claim 1 for treating or preventing inflammatory skin diseases as discussed above.
The quantity of experimentation needed: In order to translate the suggestion in Applicant’s disclosure into an actual therapeutic model with the full range of all possible treatment methods beyond those known in the art, one skilled in the art would have to undertake a novel and extensive research program to show that a hyaluronic acid conjugate composed of hyaluronic acid and either lithocholic acid, cholesterol or a combination thereof could successfully prevent any of the inflammatory skin diseases recited in claim 1 in a subject. Therefore, because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope beyond what is already known in the art, it would constitute an undue and unpredictable search and experimental burden.
Genentech, 108 F.3d at 1366, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicants fail to provide sufficient information to practice the claimed invention.
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 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.
(I) Claims 1-2, 4-6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Published 01 August 2019, US-20190231898-A1, IDS filed 01/07/2025) in view of Shi et al., (Published May 2021, Journal of Investigative Dermatology, Vol. 141, Issue 5, Supplement, Abstract Number 192, pp. S34, PTO-892).
Regarding claims 1-2, 4-6 and 8, Kim teaches treating an inflammatory disease comprising administering hyaluronic acid nanoparticles represented by Formula (I) depicted as,
PNG
media_image1.png
499
890
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Greyscale
, see pg. 10, left column, claim #1.
The Examiner respectfully notes Formula (I) depicts a hyaluronic acid conjugate composed of hyaluronic acid and 5β-cholanic acid.
Kim teaches the hyaluronic acid particles of Formula (1) may consist of hyaluronic acid and 5β-cholanic acid (e.g. the hyaluronic acid conjugate composed of hyaluronic acid and a hydrophobic substance as an active ingredient, required in claim 1, lines 3-4), see paragraph [0029].
Kim teaches the hyaluronic acid nanoparticles of Formula (I) may consist of hyaluronic acid and 5β-cholanic acid in a mass ratio of 1:0.05 to 1:0.30 (e.g. the mass ratio, required in claim 4), see paragraph [0030].
Kim teaches the hyaluronic acid conjugate of the hyaluronic acid nanoparticles of Formula (I) may be formed through self-assembly in an aqueous solution state (e.g. self-assembly, required in claim 5), see paragraph [0031].
Kim teaches the hyaluronic acid nanoparticles have a diameter of 100 nm to 500 nm (e.g. the diameter, required in claim 6), see pg. 10, left column, claim #5.
Kim teaches the pharmaceutical composition is effective in treating an inflammatory disease, wherein the inflammatory disease may be selected from the group consisting of and including dermatitis but the present invention is not limited thereto, see paragraph [0033].
Kim teaches the hyaluronic acid nanoparticles may be administered at a dose of 0.1 mg/kg (body weight) to 30 mg/kg (body weight) (e.g. a pharmaceutically effective amount, required in claim 1, line 4), see paragraph [0038].
Kim exemplifies administration to a patient (e.g. the subject in need thereof, required in claim 1, lines 4-5), see paragraph [0038].
Kim teaches a method of preparing the hyaluronic acid-5β-cholanic acid (HA-CA) nanoparticles, see paragraphs [0047]-0048].
Although Kim does not teach the hydrophobic substance is lithocholic acid as required in claims 1-8.
However, in the same field of endeavor of treating inflammatory skin diseases, Shi teaches administration of lithocholic acid (LCA) and other bile acids (BAs) by oral gavage ameliorating IL-23 MC induced-psoriasiform dermatitis (PsD) as evidenced by decreased ear thickness, epidermal thickness, and infiltration of IL-17A+ T cells in skin draining lymph nodes, see pg. S34, right column, paragraph #192.
Shi teaches LCA possessed the greatest potency in treating PsD; and administration of LCA at much lower dosing (compared to oral treatment) showed a similar anti-psoriatic effect in the IL-23 MC model, pg. S34, right column, paragraph #192.
Shi concludes that LCA improves PsD with minimal toxicity via direct inhibition of IL-17A production in T cells and by blocking CCL20-mediated trafficking and that administration of BAs may provide beneficial effects in patients with psoriasis (e.g. psoriasis, required in claim 1, line 2; and lithocholic acid, required in claim 1, line 6), pg. S34, right column, paragraph #192.
With respect to the limitation “the hydrophobic substance has a partition coefficient (LogP) within a range of 2 to 10”, required in claim 2; the Examiner reasonably interprets this limitation as a physical limitation of the hydrophobic substance conjugated to the hyaluronic acid. Since the combination of Kim and Shi teaches a hyaluronic acid conjugate consisting of lithocholic acid in treating psoriasis as the inflammatory disease, the Examiner reasonably interprets the physical limitation as discussed above is met by the teachings of Kim and Shi as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have substituted the 5β-cholanic acid as taught by Kim for the lithocholic acid as taught by Shi within the hyaluronic acid conjugates taught by Kim as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to have substituted the 5β-cholanic acid of Kim for the lithocholic acid of Shi within the hyaluronic acid conjugate taught by Kim to treat a different inflammatory disease, particularly an inflammatory skin disease as taught by Kim, which is exemplified as psoriasis as taught by Shi, as Kim already teaches treating an inflammatory skin disease, exemplifying dermatitis, which as taught by Kim is not limiting thereto with the hyaluronic acid conjugate of Kim.
One of ordinary skill in the art would have had a reasonable expectation of success to have substituted the 5β-cholanic acid of Kim for the lithocholic acid of Shi, because Kim teaches a method of making hyaluronic acid conjugates comprising 5β-cholanic acid; Kim and Shi are drawn to treating inflammatory diseases by administering a bile acid as discussed above; and wherein the Examiner notes as evidenced by the specification cholanic acid is a type of bile acid (see pg. 11, paragraph [0046]).
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Published 01 August 2019, US-20190231898-A1, IDS filed 01/07/2025) and Shi et al., (Published May 2021, Journal of Investigative Dermatology, Vol. 141, Issue 5, Supplement, Abstract Number 192, pp. S34, PTO-892) as applied to claims 1-2, 4-6 and 8 above, and further in view of Yang et al. (Published 08 October 2020, WO-2020205937-A1, PTO-892 mailed 03/26/2026).
Kim and Shi address claims 1-2, 4-6 and 8 as written above. Kim further teaches the pharmaceutical composition may be administered orally or parenterally (e.g. intravenously, subcutaneously, intraperitoneally, or topically), see paragraph [0038].
Although Kim does not explicitly teach wherein the hyaluronic acid conjugate is administered transdermally, required in claim 7.
However, in the same field of endeavor of administering a hyaluronic acid conjugate composed of hyaluronic acid and a bile acid, Yang exemplifies hyaluronic acid nanoparticles containing an anticancer agent, see abstract. Yang further exemplifies said nanoparticles are made up of hyaluronic acid conjugated to hydrophobic moieties, and wherein the hydrophobic moieties are steroid based compounds such as 5β-cholanic acid, see abstract.
Yang teaches the particles can be administered by a variety of routes including the oral, transdermal, subcutaneous or intravenous routes, see pg. 18, lines 20-25.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated wherein the hyaluronic acid conjugate composed of hyaluronic acid and lithocholic acid as taught by the combination of Kim and Shi is administered transdermally as taught by Yang above in order to treat psoriasis as taught by the combination of Kim and Shi above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results.
One of ordinary skill in the art would have been motivated to incorporate the transdermal administration taught by Yang to administer the hyaluronic acid conjugate consisting of hyaluronic acid and lithocholic acid in treating psoriasis as taught by Kim and Shi as discussed above. One of ordinary skill in the art would have had a reasonably expectation of success to have incorporated the teachings of Yang into the method of Kim and Shi as discussed above, because both Yang and Kim are drawn to administering hyaluronic acid conjugate particles composed of hyaluronic acid conjugated to hydrophobic moieties, particularly bile acids as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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