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 .
DETAILED ACTION
This action is in response to Applicant’s amendment filed February 27, 2026 in reply to the Non-final Office Action mailed January 12, 2026. Claims 1, 8, 17, and 22 have been amended; and claims 3, 19 and 20 have been canceled. Claims 2, 6, and 11-16 have been withdrawn. Claims 1, 4, 5, 7-10, 17, 18, 21, and 22 are under examination in the application.
Withdrawal of Prior Claim Rejections - 35 USC § 112(a)
Claims 8, 17, and 22 have been satisfactorily amended to remove new matter. Therefore, the 35 USC 112(a) rejection presented in the Non-final Office Action mailed January 12, 2026 is hereby withdrawn.
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.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8, as now amended, which depends from claim 1, stipulates in a wherein clause that “the nano-liposomes consist of multi-layer vesicles of…DOTAP”, which renders the claim indefinite for the following reasons:
1. Claim 1 provides that the nano-liposomes necessarily contain mRNA. However, claim 8 appears to require that the nano-liposomes necessarily consist of DOTAP and thus would necessarily exclude the mRNA. One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of the claimed subject matter.
2. One of ordinary skill in the art would generally understand a liposome to be a spherical vesicle having at least one lipid bilayer surrounding a core, typically an aqueous or hydrophilic core that can contain a drug. While one of ordinary skill in the art would understand that a liposome can be a multi-layer vesicle, and that the lipid bilayer can consist of DOTAP, one of ordinary skill in the art would not understand the notion that a liposome consists of “multi-layer vesicles of DOTAP”, in view of the fact that the liposome itself as a whole is but a vesicle. One of ordinary skill in the art would generally understand that the lipid bilayer component is not a vesicle, nor is any lipid compound contained therein a vesicle. One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of the claimed subject matter.
***It would appear that Applicant intends the limitation of claim 8 to perhaps be e.g. “wherein the nano-liposomes are multi-layer vesicles whose lipid portion consists of DOTAP”. However, this is clearly not what the claim as presented actually says.
Claim Interpretation
Claim 4 has been amended to stipulate in a wherein clause that “the CXCL9 molecules are present in a concentration of about 250 to 1500 ng/ml of the biocompatible, nanocomposite hydrogel composition”. Claim 4 previously stated that “CXCL9 molecules are present in a concentration of about 250 to 1500 ng/ml of the hydrogel material”. The specification discloses, in paragraph [0079] that “CXCL9 molecules are present in a concentration of about 250 to 1500 ng/ml of the hydrogel material”. In paragraph [0061], the specification discloses that “a plurality of CXCL9 molecules” are present “in the hydrogel”, and that “in embodiments, the CXCL9 molecules are present in an amount of about 250 ng/ml to 1500 ng/ml, such as, but not limited to, about 500 ng/ml”. Consistent with previous interpretations, “in the hydrogel” is being interpreted to mean “in the hydrogel material”. Indeed, the limitation of claim 1 about “a plurality of CXCL9 molecules in the hydrogel” is being interpreted as the CXCL9 molecules are in the hydrogel material. Since the volume of the hydrogel material is being interpreted as essentially the same as the volume of the hydrogel composition as a whole, the mass of CXCL9 in the volume of the hydrogel material is being interpreted as essentially the same as the mass of CXCL9 in the volume of the hydrogel composition as a whole.
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, 4, 5, 7-10, 17, 18, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Olson et al. (U.S. Patent Application Pub. No. 2022/0143210), in view of Okano et al. (Japanese Patent Application Pub. No. JP 05229934 A), Sayour et al. (Int J Mol Sci. 2018; 19: 2890; i.e. “Sayour I”), and Sayour et al. (Oncoimmunology. 2017; 6(1): e1256527; i.e. “Sayour II”).
***Applicant is advised that Olson et al. is an application for patent published under section 122(b) which names another inventor and was effectively filed before the effective filing date of the claimed invention. Olsen et al. is a National Stage entry of a WIPO application filed February 27, 2020, which claims priority to U.S. Provisional Patent Applications filed on April 1, 2019 and February 27, 2019. The effective filing date of the present application is August 14, 2020.
Applicant Claims
Applicant’s elected subject matter is directed to a hydrogel composition comprising polyethylene glycol (i.e. as the hydrogel material), CXCL9, and nanoliposomes loaded with mRNA corresponding to a tumor antigen; wherein the nanoliposomes are multilayer vesicles of DOTAP and have an average diameter of 70-200 nm; wherein the hydrogel composition comprises about 5-550 µg of nanoliposomes; and wherein the nanoliposomes include about 1 µg mRNA to about 5-10 µg of nanoliposomes.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Olson et al. disclose a hydrogel composition for treatment of cancer comprising polyethylene glycol (i.e. as the hydrogel material) and a chemokine, wherein the chemokine can be e.g. CXCL9 (paragraphs 0008, 0010, 0011, 0024, 0053, 0056, 0057).
Okano et al. disclose a hydrogel composition comprising e.g. polyethylene glycol (i.e. as the hydrogel material) and liposomes containing an active agent.
Sayour I discloses multilamellar nanoliposomes for treatment of cancer comprising DOTAP and loaded with mRNA corresponding to a tumor antigen, which nanoliposomes can be employed for intratumoral delivery.
Sayour II discloses that nanoliposomes comprising DOTAP and loaded with mRNA corresponding to a tumor antigen for use in cancer treatment have an average diameter of 70-200 nm; have an optimal ratio of 1 µg mRNA to 10-20 µg DOTAP; and are employed in an amount of e.g. 400 µg (i.e. 25 µg mRNA plus 375 µg of DOTAP).
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Olson et al. do not explicitly disclose that the hydrogel composition further comprises multilayer nanoliposomes of DOTAP with an average diameter of 70-200 nm; and containing 1 µg mRNA to about 5-10 µg of nanoliposomes. These deficiencies are cured by the teachings of Okano et al., Sayour I, and Sayour II.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Olson et al., Okano et al., Sayour I, and Sayour II, outlined supra, to devise Applicant’s presently claimed hydrogel composition.
Olson et al. disclose a hydrogel composition for treatment of cancer comprising polyethylene glycol (i.e. as the hydrogel material) and CXCL9; wherein the hydrogel composition is locally administered to a malignant tumor and stimulates the immune system to eliminate the malignant tumor cells. Since Okano et al. disclose that a hydrogel composition comprising e.g. polyethylene glycol (i.e. as the hydrogel material) can further contain liposomes loaded with the active agent for controlled delivery and release; since Sayour I discloses that multilamellar nanoliposomes comprising DOTAP and loaded with mRNA corresponding to a tumor antigen can be employed for intratumoral delivery to stimulate the immune system for treating cancer, with the advantage that mRNA encoding for tumor associated or tumor specific epitopes harness the immune system in a personalized and directed manner against tumor specific antigens which can serve as a more immunogenic and expeditious trigger of anti-tumor immunity; and since Sayour II discloses that nanoliposomes comprising DOTAP and loaded with mRNA corresponding to a tumor antigen for use in cancer treatment have an average diameter of 70-200 nm; have an optimal ratio of 1 µg mRNA to 10-20 µg DOTAP; and are employed in an amount of e.g. 400 µg (i.e. 25 µg mRNA plus 375 µg of DOTAP); one of ordinary skill in the art would thus be motivated to further include about 400 µg nanoliposomes comprising DOTAP and loaded with mRNA corresponding to a tumor antigen having an average diameter of 70-200 nm and an optimal ratio of 1 µg mRNA to 10-20 µg DOTAP in the Olson et al. hydrogel composition, with the reasonable expectation that the resulting hydrogel composition, upon local administration to a malignant tumor, will have the advantages of mRNA encoding for tumor associated or tumor specific epitopes harnessing the immune system in a personalized and directed manner against tumor specific antigens which can serve as a more immunogenic and expeditious trigger of anti-tumor immunity.
Olson et al. disclose that the chemokine is present in the amount of 121 ng/ml of the hydrogel composition (see e.g. paragraph 0178). Applicant claims the CXCL9 chemokine is present in the amount of “about” 250-1500 ng/ml of the “hydrogel material”. From claim 22, it appears the “hydrogel”, presumably, the “hydrogel material” can be only 50% of the volume of the hydrogel composition as a whole. Hence, Applicant provides for a CXCL9 amount of “about” 125 ng/ml of the hydrogel composition as a whole. Olson et al. thus appear to meet this limitation.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Potentially Allowable Subject Matter and Rejoinder
As previously noted, Applicant potentially has allowable subject matter if claim 1 can be amended to necessarily exclude Olsen’s immune checkpoint inhibitors. Upon allowance of claim 1, Applicant is then eligible for rejoinder of claim 13, directed to “a method of treating or preventing a disease in a subject” by administering a vaccine comprising the hydrogel composition of claim 1.
Although claim 13 remains withdrawn at this time, in the interest of compact prosecution, it is noted here as a courtesy that if claim 13 as now presented is rejoined and examined, claim 13 would be rejected under 35 USC 112 for scope of enablement. Indeed, Applicant is advised that there is clearly a lack of enablement for treating any and all diseases known to man. Further, Applicant is also not enabled for “preventing” any and all diseases known to man, including cancer and infectious diseases, even if Applicant is enabled for “treating” cancer and infectious diseases.
Response to Arguments
Applicant's arguments filed February 27, 2026 have been fully considered but they are not found persuasive.
i) Applicant contends that due to “the consisting of transitional phrase”, the claimed composition does necessarily “exclude the chemokines of Olsen”.
The Examiner, however, would like to point out the following:
1. Contrary to Applicant’s assertion, claim 1, as now presented, does not necessarily exclude immune checkpoint inhibitors.
2. In the Non-final Office Action mailed January 12, 2026, it was noted that “Claim 3, which depends from claim 1, stipulates in a wherein clause that “the biocompatible hydrogel material is polyethylene glycol (PEG)”. This is being interpreted as the “hydrogel material” element is exclusively PEG (i.e. “consists of” PEG), which would exclude all other elements, such as checkpoint inhibitors. Claim 3 is thus objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims”.
3. However, Applicant did not amend claim 1 by merely moving the limitation of claim 3 into claim 1 only. Applicant also amended claim 1 by providing that one of the elements of the claimed hydrogel composition is “phosphate buffered saline (PBS)”. While one of ordinary skill in the art would recognize that phosphate buffered saline would necessarily contain certain key elements, such as water, NaCl, KCl, Na2HPO4, and KH2PO4, phosphate buffered saline is open to the further inclusion of essentially any other ingredient, including checkpoint inhibitors. Indeed, as one of ordinary skill in the art would recognize, phosphate buffered saline is often used as the standard carrier for the delivery of checkpoint inhibitors. Clearly, then, in contrast to Applicant’s assertion, the presently claimed composition, as now presented, does not necessarily exclude Olsen’s checkpoint inhibitors.
For the foregoing reasons, the 35 USC 103 rejection is hereby maintained.
Conclusion
No claims are allowed.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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/DAVID BROWE/Primary Examiner, Art Unit 1617
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