Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined pursuant to the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
The Examiner acknowledges Applicants’ Response to the Action of 9 April 2026, filed on 15 May 2026. Applicants did not amend any claims. Upon finalization and entry of the Restriction/Election Requirement (see below), claims 1 – 17 will be available for substantive examination.
Response to Restriction/Election Requirement
Applicants’ election, with traverse, of the invention of Group I, claims 1 – 17 in the Response filed on 15 May 2026 is acknowledged. The traversal is on the grounds that “the method of claim 1 cannot be practiced with a composition using a glycosaminoglycan other than hyaluronic acid, or with a non-crosslinked composition.” It is the Examiner’s position that Applicants’ argument is not persuasive. As one of ordinary skill in the art would recognize, it is the dust mite antigen component of the compositions prepared according to the method of the invention that induces an immune response. In order for Applicants’ argument to be persuasive, it would require proof or evidence that the immune response that the composition of the invention is designed to elicit would not occur without a cross-linked hyaluronic acid hydrogel. Looking to the prior at references cited in Applicants’ IDS of 20 September 2023, both of the references cited therein address the contribution of the dust mite antigen itself to the desired immune response and only cite to the use of a cross-linked HA hydrogel in reducing possible allergic responses to the injection. Nor does Applicants’ specification provide any data supporting a contention that hydrogel carriers for dust mite antigens other than cross-linked HA, or other GAG’s, would not be able to elicit an immune response, as desired. Consequently, Applicants’ arguments are unpersuasive, and the Restriction Requirement is hereby made FINAL.
The Examiner further acknowledges Applicants’ election of the species Dermatophagoides pteronyssinus from the genus of dust mite.
Claims 18 - 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Accordingly, claims 1 – 17 are subject to examination on the merits, to the extent that the house dust mite is Dermatophagoides pteronyssinus, to which the grounds of rejection set forth below are applicable.
Information Disclosure Statement
The Examiner has considered the information disclosure statement (IDS) filed 20 September 2023, which is now of record in the file.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Rejections Pursuant to 35 U.S.C. § 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.
Claim 1 – 26 are rejected pursuant to 35 U.S.C. § 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA , the Applicant, regards as the invention.
The preamble of claim 1 states that the invention is directed to a method “for treating immunotherapy of allergic diseases.” In contrast, the Abstract of Applicants’ specification discloses that the “present invention relates to a composition for immunotherapy of allergic diseases (see also, ¶¶[0002], [0012]1).” In this regard, the Examiner notes that one of ordinary skill in the art would recognize that antigen compositions have established utility for the “treatment of allergic diseases,” and NOT for “treating immunotherapy” of allergic diseases. Consequently, the skilled practitioner would be uncertain as to what the claimed composition was intended to treat.
To determine whether a claim is patentable over the prior art, the claim terms must first be construed. Genentech v. Wellcome Foundation, 29 F.3d 1555, 1563-64, 31 USPQ2d 1161, 1167-68 (Fed. Cir. 1994); MPEP § 2164.04. Claim terms must be given their broadest reasonable interpretation consistent with the specification; that is, their plain meaning, unless Applicant has otherwise defined the term or terms in question in the specification. In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000); In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989). However, if Applicant elects to define specific claim terms, he/she must do so with reasonable clarity, deliberateness, and precision, and must set out his uncommon definition so as to give one of ordinary skill in the art notice of the change in meaning. Intellicall, Inc. v. Phonometrics, Inc., 952 F.2d 1384, 1387-88, 21 USPQ2d 1383, 1386 (Fed. Cir. 1992).
In the instant case, the Examiner notes that the phrase “for treating immunotherapy of allergic diseases,” only occurs in claim 1 of the application as filed on 20 September 2023. In the Abstract and Specification, the disclosures referenced above include what is reasonably interpreted as a correct technical description relating to clinical use of the disclosed compositions: “[t]he present invention relates to a composition for immunotherapy of allergic diseases.”
In light of this disclosure, and in the interests of compact prosecution, the Examiner shall interpret the phrase in question for examination purposes as referring to use of compositions for immunotherapy of allergic diseases.
In addition, claim 1 recites a limitation directed to the composition of the invention being a “crosslinked product of house dust mite antigens and hyaluronic acid hydrogels.” It is the Examiner’s position that one of ordinary skill in the art would reasonably interpret, not only technically, but both grammatically and logically, the phrase in question to be directed to a composition comprising a “crosslinked product” where the crosslinking is between the antigens and the hydrogels. First of all, a skilled practitioner would recognize that it would be technically unlikely to crosslink a house dust mite antigen to hyaluronic acid to form a hydrogel, at least on the basis that hyaluronic acid must be crosslinked in order to display the semi-solid properties attributed to hydrogels. See, for example, Chandrasekharan, A., et al, J. Polym. Sci., Part A: Polym. Chem 57: 522 – 530 (2019) (“Chandrasekharan (2019)”).
In looking to Applicants’ specification, the Examiner notes that the specification discloses, at, for example, ¶¶[0009], [0010], [0012], [0013], language tracking the limitation cited above. However, the disclosure at ¶[0038] is more instructive:
The composition of the present invention utilizes hydrogels as a delivery material for house dust mite antigens. The immunotherapeutic agent using injectable HA hydrogels employed in the present invention allows easy subcutaneous injection of a liquid hydrogel containing a large amount of allergens. Upon exposure to visible light or blue light, this liquid hydrogel transforms into a viscous hydrogel, thereby slowing its degradation. This ensures a consistent degradation of an allergen load that can induce immune tolerance without triggering anaphylaxis. Furthermore, the consistent rate of degradation of the allergen-loaded hydrogel resolves the inconvenience of frequently administering allergens through subcutaneous injection. Before photo-crosslinking occurs, the hydrogel remains in a liquid state, allowing the use of thin injection needles, which feature the advantage of not causing pain during the injection process.
This disclosure clearly exemplifies an absence of any disclosure that would support a crosslinking between the HA and the dust mite antigens (“a crosslinked product”) to form the hydrogel. Further, looking at Example 1, the hyaluronic acids that were photocrosslinked to produce a hydrogel were thiolated and methacrylated hydrogels, and it was the presence of these modifying groups that enabled crosslinking of HA in either visible or UV light to create the hydrogel. Consequently, it is the Examiner’s position that the claim is reasonably understood to be directed to the use of a composition for treating allergic diseases, wherein the composition comprises a mixture of crosslinked hyaluronic acid and house dust mite antigens, which, in the interests of compact prosecution is the interpretation applied in examination of the claims.
Claims 2 - 17 are included in this rejection because they depend from claim 1 and because they do not remedy the noted ambiguity.
Claim 9 recites the limitation "the 750 µg of the house dust mite….". There is insufficient antecedent basis for this limitation in the claim. Base claim 1 does not recite any concentration or amount of the house dust mite antigen, thus it is unclear what “the 750 µg” is referencing.
Claim 9 and 10 lack antecedent basis in reciting “the house dust mite antigen” and “the antigen”. Base claim 1 recites “house dust mite antigens”, which encompasses multiple house dust mite antigens. Thus, it is unclear whether “the house dust mite antigen” and “the antigen” (singular), refer to just one, more than one or all of the house dust mite antigens. Amending claims 9 and 10 to recite “the house dust mite antigens” would overcome this rejection.
Claim 9 is indefinite in reciting “wherein the 750 µg of the house dust mite antigen is comprised based on 100 µL of the hyaluronic acid.” It is unclear what is contemplated by the phase, as it is unclear whether the administered composition of claim 1 comprises 750 µg of the house dust mite antigens in 100 µL of the hyaluronic acid and is required by the claim, or whether the 750 µg of the house dust mite antigens is based on 100 µL of the hyaluronic acid in order to specify a ratio of the two components that may be present. As written, one skilled in the art would not be reasonably apprised of the metes and bounds of the claim.
Rejections Pursuant to 35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections pursuant to 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.
Claims 1 – 7, 13, 16, and 17 are rejected pursuant to 35 U.S.C. § 102(a)(1) as being anticipated by International Congress of 50th Anniversary KAAACI, 5 June 2022 (“KAAACI (2022)”).
KAAACI (2022) discloses the application of allergen-specific immunotherapy (AIT) with injectable compositions comprising hyaluronic acid (HA) hydrogels that contain house dust mites (HDM’s), wherein compositions comprise one or more hydrogels that are crosslinked via a visible (VIS) light-induced thiol-ene reaction, wherein the compositions comprised a thiolated HA hydrogel, a methacrylated HA hydrogel, and a mixture of a thiolated 4-arm poly(ethylene glycol) hydrogel and a methacrylated HA hydrogel, in 1:1 and 2:1 volume ratios, wherein mice were sensitized by administering HDM extract intranasally for five days, and received one subcutaneous injection of each of the three hydrogel preparations followed by irradiating with blue light through the skin, wherein all groups of test animals exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage compared to the positive control, indicating that administration of the HA hydrogel compositions reduced allergic symptoms and induced tolerance in a murine model of rhinitis.
Consequently, KAAACI (2022) discloses each and every limitation of the claims at issue, rendering them anticipated pursuant to 35 U.S.C. § 102(a)(1).
Rejections Pursuant to 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 that 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 of this title, 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 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 absent any evidence to the contrary. Applicants are advised of the obligation pursuant to 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 – 7 and 10 - 17 are rejected pursuant to 35 U.S.C. § 103, as being obvious over KAAACI (2022) in view of Lee, H., et al., Reactive and Functional Polymers 131: 29 – 35 (2018) (“Lee (2018)”), and US 2016/0251403 A1 to Lundegaard, C., et al., published 1 September 2016 (“Lundegaard ‘403”).
The Invention As Claimed
Applicants claim a method for treating immunotherapy of allergic diseases, the method
comprising administering a composition comprising the crosslinked product of house dust mite antigens and hyaluronic acid hydrogels to a subject in need thereof, wherein the hyaluronic acid is substituted with a thiol group or a methacrylate group, wherein the hydrogel comprises hyaluronic acid substituted with a thiol group (SH-HA) and hyaluronic acid substituted with a methacrylate group (MA-HA), wherein the volume ratio of hyaluronic acid substituted with a thiol group and hyaluronic acid substituted with a methacrylate group is 1 :1, wherein the hydrogel comprises hyaluronic acid and polyethylene glycol, wherein the hyaluronic acid is substituted with a methacrylate group, wherein the polyethylene glycol is substituted with a thiol group, wherein the antigen is a crude extract, wherein the composition further comprises a photoinitiator, wherein the photoinitiator is riboflavin, wherein the crosslinking of the crosslinked product is induced by visible light, wherein the house dust mite is Dermatophagoides pteronyssinus, wherein the composition further comprises an adjuvant, wherein the allergic disease is induced by house dust mites, and wherein the allergic disease is rhinitis, asthma, conjunctivitis, urticaria, contact dermatitis, or atopic dermatitis.
The Teachings of the Cited Art
The disclosures of KAAACI (2022) are relied upon as set forth above. The reference does not explicitly disclose use of compositions wherein the antigen is a crude extract, wherein the composition further comprises riboflavin as a photoinitiator, wherein the house dust mite is Dermatophagoides pteronyssinus, and wherein the composition further comprises an adjuvant, and the allergic disease is rhinitis, asthma, conjunctivitis, urticaria, contact dermatitis, or atopic dermatitis. The teachings of Lee (2018) and Lundegaard ‘403 remedy those deficiencies.
Lee (2018) discloses hyaluronic acid (HA) hydrogels crosslinked via thiol-ene reaction initiated by visible blue light exposure in the presence of riboflavin phosphate (RFP), wherein the gelation procedure is rapid and proceeds as effectively with exposure to blue light as it does with UV light, which triggered gelation that proceeds over about 5 min at 36 °C after an initial small change in modulus upon light exposure, and wherein a riboflavin phosphate-based, blue light-initiated photo-reaction to gelate HA is an effective and promising modality for applications where in situ gelation is desired (see Abstract), wherein blue light (BL) triggered gelation of HA via thiol-ene reaction between methacrylated HA (MA-HA) and thiolated HA (SH-HA) (see p. 29, 2nd col., 2nd para.), wherein methacrylated HA (MA-HA) and thiolated HA (SH-HA) were dissolved in PBS at a concentration of 10 mg/mL, and the solutions mixed at a 1:1 ratio, and riboflavin dissolved in PBS was added to the mixture of modified HA solution, followed by irradiation exposure times of 20 s for UV and 40 s for blue light (BL) (see p. 30, 1st col., 3rd para.)
Lundegaard ‘403 discloses combinations of peptides or variants thereof derived from a portion of house dust mite allergens and the use of the peptides in relieving an immune response caused by a dust mite (see Abstract), wherein the combination of peptides is used as an “allergy vaccine” in the treatment of allergy to a house dust mite allergen, wherein the peptide combinations derive from one or more of the house dust mite allergens, and are shown to produce a T-cell response in many donors and to have a satisfactorily high worldwide HLA Class II coverage (see ¶[0013]), wherein the peptides are used in a pharmaceutical composition in a method for relieving or reducing (e.g., treating) an immune response triggered by an allergen of a dust mite (e.g., house dust mite) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the composition (see ¶[0040]), wherein the compositions comprise peptides from an allergen of both the house dust mite species Dermatophagoides farinae and Dermatophagoides pteronyssinus (see ¶[0093]), wherein the peptide may be formulated (e.g., mixed together) with immune-modifying agents like adjuvants that may be any conventional adjuvant, including but not limited to oxygen-containing metal salts, e.g., aluminum hydroxide, chitosan, heat-labile enterotoxin (LT), cholera toxin (CT), cholera toxin B subunit (CTB), polymerized liposomes, mutant toxins, e.g. LTK63 and LTR72, microcapsules, interleukins (e.g. IL-1 BETA, IL-2, IL-7, IL-12, INFGAMMA), GM-CSF, MDF derivatives, CpG oligonucleotides, LPS, MPL, MPL-derivatives, phosphophazenes, Adju-Phos®, glucan, antigen formulation, liposomes, DDE, DHEA, DMPC, DMPG, DOC/Alum Complex, Freund's incomplete adjuvant, ISCOMs®, LT Oral Adjuvant, muramyl dipeptide, monophosphoryl lipid A, muramyl peptide, and phospatidylethanolamine (see ¶[0348]), and wherein the compositions treat allergies to dust mites that clinically present as atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anaphylaxis, and/or hay fever (see ¶[0362]).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to treat allergic diseases with injectable compositions comprising hyaluronic acid (HA) hydrogels that contain house dust mite (HDM) antigens, wherein the compositions comprise one or more hydrogels that are crosslinked via a visible (VIS) light-induced thiol-ene reaction, wherein the compositions comprised a thiolated HA hydrogel, a methacrylated HA hydrogel, and a mixture of a thiolated 4-arm poly(ethylene glycol) hydrogel and a methacrylated HA hydrogel, in 1:1 and 2:1 volume ratios, wherein mice were sensitized by administering HDM extract intranasally for five days, and received one subcutaneous injection of each of the three hydrogel preparations followed by irradiating with blue light through the skin, wherein all groups of test animals exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage compared to the positive control, indicating that administration of the HA hydrogel compositions reduced allergic symptoms and induced tolerance in a murine model of rhinitis, as taught by KAAACI (2022), wherein the hyaluronic acid (HA) hydrogels are crosslinked via thiol-ene reaction initiated by visible blue light exposure in the presence of riboflavin phosphate (RFP), wherein the gelation procedure is rapid and proceeds as effectively with exposure to blue light as it does with UV light, which triggered gelation that proceeds over about 5 min at 36 °C after an initial small change in modulus upon light exposure, and wherein a riboflavin phosphate-based, blue light-initiated photo-reaction to gelate HA is an effective and promising modality for applications where in situ gelation is desired, wherein the thiol-ene reaction crosslinked the methacrylated HA (MA-HA) and thiolated HA (SH-HA), upon irradiation for 40 s with blue light (BL), as taught by Lee (2018), and wherein the compositions comprise peptides from an allergen of the house dust mite species Dermatophagoides pteronyssinus, and wherein the peptide composition is formulated with immune-modifying agents like adjuvants that may be any conventional adjuvant, and wherein the compositions treat allergies to dust mites that clinically present as diseases such as atopic dermatitis, contact dermatitis, and allergic rhinitis, as taught by Lundegaard ‘403. One of skill in the art would be motivated to do so, with a reasonable expectation of success in so doing, by the teachings of Lee (2018) to the effect that the gelation procedure is rapid and proceeds as effectively with exposure to blue light as it does with UV light in the presence of riboflavin phosphate (RFP) (see Abstract), and by the teachings of Lundegaard ‘403 as to the recognized utility of adjuvants in enhancing the immunomodulatory effects of vaccine compositions (see ¶[0348]).
With respect to claim 10, which claim recites a limitation directed to the antigen being “a crude extract,” the Examiner notes that the cited references, such as KAAACI (2022) do not expressly characterize the dust mite antigens as crude extracts. However, the Examiner further notes that the reference does not disclose the use of antigens that have been processed to remove substances other than the major allergens, leading to the reasonable presumption that the antigens are from a crude extract.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 1 – 7 and 10 – 17 would have been obvious within the meaning of 35 USC § 103.
Claim 8 is rejected pursuant to 35 U.S.C. § 103, as being obvious over KAAACI (2022) in view of Lee (2018), and Lundegaard ‘403, as applied in the above rejection of claims 1 – 7 and 10 – 17, and further in view of US 2022/0370419 A1 to Jarrett, P., et al., claiming priority to 12 May 2015 (“Jarrett ‘419”).
The Invention As Claimed
The invention with respect to claims 1 and 5 is described above. In addition, Applicants claim a method for treating allergic diseases comprising administering a composition comprising crosslinked hyaluronic acid hydrogels and house dust mite antigens, wherein the hydrogels comprise hyaluronic acid and polyethylene glycol at a ratio from 1:1 to 4:1.
The Teachings of the Cited Art
The disclosures of KAAACI (2022) in view of Lee (2018), and Lundegaard ‘403, are relied upon as applied in the above rejection of claims 1 – 7 and 10 – 17. The references do not disclose hydrogels that comprise hyaluronic acid and polyethylene glycol at a ratio from 1:1 to 4:1. The teachings of Jarrett ‘419 remedy that deficiency.
Jarrett ‘419 discloses hydrogels used for drug delivery to treat various medical conditions by delivering a therapeutic agent to target tissue in a hydrogel formed in situ (see Abstract), wherein hydrogels can be formed from hyaluronic acid crosslinked via its native nucleophiles, or after it is derivatized with functional groups (see ¶[0078]), wherein the hydrogels can be formed with a polyethylene glycol-containing precursor (see ¶[0088]), and wherein, in an exemplified embodiment, hydrogel compositions were prepared with a 4.8% polyethylene glycol (PEG) formulation and a 1% formulation of hyaluronic acid (see Example 1, ¶¶[0143] – [0168]; see also, TABLE 3).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to treat allergic diseases with injectable compositions comprising hyaluronic acid (HA) hydrogels that contain house dust mite (HDM) antigens according to the teachings of KAAACI (2022), Lee (2018), and Lundegaard ‘403, wherein the hydrogels further comprise polyethylene glycol at a concentration of 4.8% and hyaluronic acid at up to 2.5%, as taught by Jarrett ‘419. One of ordinary skill in the art would have been motivated to do so, with a reasonable expectation of success by the express teachings of Jarrett ‘419 to the effect that a combination with HA results in improved viscosities (see ¶[0057]).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claim 8 would have been obvious within the meaning of 35 USC § 103.
NO CLAIM IS ALLOWED.
CONCLUSION
Any inquiry concerning this communication or any other communications from the examiner should be directed to Daniel F. Coughlin whose telephone number is (571)270-3748. The examiner can normally be reached on M-F 8:30 am - 5:30 pm.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, David J Blanchard, can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/DANIEL F COUGHLIN/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/ Supervisory Patent Examiner, Art Unit 1619
1 Paragraph references are to US 2024/0307529 A1
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