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 .
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.
This office action is a response to applicant’s election submitted July 2, 2026. Claims filed December 29, 2023 are examined herein wherein claims 1-13, 15, 17-23, 30 and 34-38 were preliminarily amended.
Claims 1-38 are pending in this application.
Priority
This application is a 371 of PCT/IB2022/056615 filed 07/19/2022 and claims foreign priority to IT102022000006149 filed 03/29/2022 and IT102021000019544 filed 07/22/2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copies have been received.
Election
Applicant’s election without traverse of Group I claims 1-20 in the July 2, 2026 is acknowledged.
Claim 21-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 2, 2026.
Thus claims 1-20 are examined herein.
Drawings
The drawings are objected to because:
Figures 1-2 and 11-12 have blurry Y-axis labels rendering them illegible.
In Figures 3-5 the terms THP-1-X-Blue™, RAW-Blue™, and HEK-Blue™ which are tradenames or marks used in commerce, has been noted in this application (See USPTO trademark registry). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Figures 3-4 and 10 appear to utilize the unit “uM”, but it is believed the unit “µM” is meant to be used.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
On page 3, lines 14-15, structure SDZ MRL 953 has overlapping atoms/bonds:
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On page 5, lines 14-15, structure FP112 is blurry rendering the structure illegible, the negative charges look like radicals. It is suggested to further correct the blurriness of the structural formulas listed on pages 6-11, 14-15, 17-26, 32-33, 37-39, and 50-51. See page 14, lines 4-5 for an example of a clear structural formula.
The use of the terms THP-1-X-Blue™, RAW-Blue™, and HEK-Blue™ (pg. 5, line 23, pg. 28, line 9, pgs. 11-13, description of drawings, pg. 56, lines 5-6, 8-9, 14, 19-20, 26-30, 35, pg. 57, lines 1, 4, 8, 13, 19-20, pg. 58, lines 1, 5, 13, 16,) which are tradenames or marks used in commerce, has been noted in this application (See USPTO trademark registry). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Interpretation
Claim 12 recites “A vaccine adjuvant consisting of the compound as defined in claim 1.” The broadest reasonable interpretation of the claim includes the compound itself.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 11 and 20: Claims 11 and 20 recite inter alia, “wherein said diseases are…. apoptosis….”. Including the phrase “apoptosis” within the list of diseases leads to a lack of clarity that renders the claim indefinite. It is unclear whether the phrase is including “apoptosis” which is programmed cell death, as a disease to be treated, whether it means that the compound acts by triggering apoptosis or whether it treats diseases that involve pathological apoptosis. A person of ordinary skill in the art would be unable to ascertain the metes and bounds of the invention, rendering the claims indefinite.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 4-6, 8, 10-12, and 15-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hasegawa (JP-H05202082 cited in previous action). The English translation relied upon was provided in a previous action.
Regarding claims 1-2, 4-6, 8, 10-12, 15-20: Hasegawa teaches compounds which are Lipid A analogs having Lipid A-like activity useful as drugs such as an immunostimulant and an antitumor agent (i.e. anticancer, English translation, para. 1, para. 0001). Hasegawa teaches the compounds activate immunity (i.e. vaccine, English translation, pg. 1, para. 0002). Hasegawa teaches a compound of the following formula I
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wherein R1 to R3 are H or OH; l, m, n are 6-14), e.g. 2-deoxy-4-O-phosphono-2-tetradecanamide-1-O-tetradecanoyl-3-O- tetradecanoyl-alpha-D-glucopyranose (i.e. each acyl has 14 C, Original document, abstract, pg. 3, middle of page, English translation, abstract). Hasegawa teaches the invention also includes pharmaceutically acceptable salts of the compounds, including sodium salts (English translation, pg. 2, para. 0012). Hasegawa teaches both isolated isomers are included in the invention (English translation, pg. 2, para. 0012). Hasegawa teaches the compounds are usually administered systemically or locally, orally or parenterally (English translation, pg. 3, para. 0026). Hasegawa teaches the liquid compositions for oral administration include pharmaceutically acceptable emulsions, solubilizers, suspensions, syrups, elixirs and the like, and generally used inert diluents, for example, purified water, ethanol, vegetable oil, emulsifier, etc. (i.e. carrier, English translation, pg. 3, para. 0026). Hasegawa teaches compositions for parenteral administration include external preparations containing one more active substances (i.e. additional active principle, English translation, pg. 3, para. 0026).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-12 and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hasegawa (JP-H05202082 cited in previous action) as applied to claims 1-2, 4-6, 8, 10-12, 15-20 above.
Regarding claims 1-2, 4-6, 8, 10-12, 15-20: Even if assuming for the sake of the argument the specific sodium salt was not anticipated over Hasegawa, the present claims would still have been rendered obvious over Hasegawa. As discussed above, Hasegawa teaches the invention also includes pharmaceutically acceptable salts of the compounds, including sodium salts (English translation, pg. 2, para. 0012). Wherein Hasegawa teaches sodium salts as a suitable alternative, the salt form of the compounds are encompassed by Hasegawa and it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
Regarding claims 3: As discussed above Hasegawa teaches the compound of claim 1.
Hasegawa does not explicitly teach wherein R1, R2, R3 (l, m, n of Hasegawa) are different from each other and within the claimed alkyl chain lengths.
However, Hasegawa further teaches l, m, n are 6-14 (Abstract). Hasegawa also demonstrates several compounds wherein chain lengths differ in individual compounds (English translation, pg. 3, last para). Hasegawa demonstrates chain lengths of 10, 12, and 14 (English translation, pg. 3, last para.).
Taken together it would have been prima facie obvious to modify the compounds of Hasegawa such that the three alkyl chain lengths differ and are within the claimed range, such as 10, 12, 14. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as Hasegawa teaches these as tolerable alkyl chain lengths are demonstrates that the alkyl chains can differ within the same compound. An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties. (See MPEP 2144.09 (I)).
Regarding claim 7: Hasegawa does not explicitly teach wherein the alkyl chains are 13, 9, or 11.
However, Hasegawa further teaches l, m, n are 6-14 (abstract). Hasegawa demonstrates chain lengths of 10, 12, and 14 (English translation, pg. 3, last para.).
Taken together it would have been prima facie obvious to modify the compounds of Hasegawa such that the three alkyl chain lengths are 13, 9, or 11 and arrive at the claimed compounds. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as Hasegawa teaches chain lengths of 10, 12, and 14, and the broad disclosure teaches chain lengths can range from 6-14. An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties. (See MPEP 2144.09 (I)).
Regarding claim 9: Although Hasegawa does not explicitly teach the beta anomer, Hasegawa teaches both isolated isomers are included in the invention (English translation, pg. 2, para. 0012). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (See MPEP 2144.09 (II)).
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hasegawa (JP-H05202082 cited in previous action) as applied to claims 1-12 and 15-20 above in view of Perri (WO 2019/092572, IDS filed December 29, 2023).
Regarding claims 12-14: Even if assuming for the sake of argument that a vaccine adjuvant was not anticipated over Hasegawa, claim 12, as well as claims 13-14 would have been rendered obvious in view of Perri.
As discussed above, Hasegawa teaches/renders obvious the compound of claim 1. Hasegawa teaches compounds which are Lipid A analogs having Lipid A-like activity useful as drugs such as an immunostimulant and an antitumor agent (i.e. anticancer, English translation, para. 1, para. 0001).
Hasegawa does not teach wherein the compound is utilized as a vaccine adjuvant or as the sole adjuvant in a vaccine composition comprising a pharmaceutically acceptable carrier and at least one pharmaceutically acceptable immunogenic antigen.
However, Perri teaches synthetic and natural proteins with a structure similar to lipid A, but with attenuated endotoxicity, are interesting candidates as vaccine adjuvants in the perspective of maintaining immunostimulatory activity while eliminating the toxic effects (pg. 2, lines 9-11). Monophosphoryl lipid A (MPL) is a molecule identical to lipid A, but with the C1 position stripped of the phosphate group through chemical modification. MPL has ~0.1 % of the inflammatory toxicity of the parent molecule, LPS, and is used as adjuvant in a series of vaccines (pg. 2, lines 12-15). However, the MPL adjuvant used nowadays is chemically heterogeneous, as produced directly from natural LPS (pg. 2, lines 16-17). The synthetic compounds named AGPs (also known as CRX adjuvants, Corixa) are comprised of a monosaccharide unit linked by glycosidation to a unit of an aminoalkyl aglycone N-acylate (pg. 2, lines 17-19). A further simplification of the structure of Lipid A still able to activate TLR4 is comprised of the monophosphorylated monosaccharide derivatives mimicking the reducing portion or the non-reducing portion of Lipid A
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(pg. 2, lines 22-25). The compounds shown above mimic lipid A are active in stimulating TLR4-dependent production of cytokines TNF-a and IL-6, or stimulating the release of inflammatory cytokines like interleukin-6 (IL-6), interleukin-8 (IL-8) and TNF-a factor (pg. 3, lines 1-10). Perri teaches comparable compounds to that of Hasegawa that activate TLR4 receptors and teach the use of the compounds as adjuvants or active principles in drug/vaccine compositions comprising the compounds (pg. 4, lines 25-30, pg. 5, lines 7-15). Perri teaches the compounds activate the immune system via activation of TLR4 activation (pg. 9, lines 3-11). Perri teaches the relevance of immune response adjuvants during vaccine administration is known, and such adjuvants substantially increase vaccine effectiveness and development of immunity, in the treated subject toward antigens present in the vaccine (pg. 9, lines 12-17). Perri teaches vaccine composition according to the invention could therefore comprise the compound as described herein at least one pharmaceutically acceptable carrier and at least one antigenic compound able to induce an immune response to a given pathology (pg. 9, lines 21-24).
Taken together, it would have been prima facie obvious to utilize the compounds of Hasegawa in a vaccine composition, or as a vaccine adjuvant in a composition comprising one pharmaceutically acceptable carrier and at least one antigenic compound able to induce an immune response to a given pathology as suggested by Perri. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as it is a known application in the art for lipid A analogs having lipid A activity that have immunostimulating activity in order to increase vaccine effectiveness and development of immunity, in the treated subject toward antigens present in the vaccine.
Conclusion
No claims are allowed in this action.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Peri (IT 201800000728, cited on PTO-892, the English translation relied upon was provided and cited on PTO-892) teaches novel TLR4 antagonists, compositions comprising them and their use as medicinal products (English translation, pg. 1, para. 1).
Hasegawa (JP-H05202083, cited on PTO-892, the English translation relied upon was provided and cited on PTO-892) teaches a novel 4,6-O-hydroxyphosphoryl-glucosamine derivative having lipid A-like activity which is useful as a drug such as an immunostimulant and an antitumor agent (English translation, pg. 1, para. 0001).
Bazin-Lee (WO 2019/157509, cited on PTO-892) teaches Toll-like receptor (TLR) ligands having an allose-based core are stable in aqueous formulation and are useful in treating, preventing, or reducing susceptibility to diseases or conditions mediated by TLRs, such as cancer, infectious disease, allergy, autoimmune disease, sepsis, and ischemia reperfusion (abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693
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