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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-16 and 20 in the reply filed on April 9, 2026 is acknowledged.
Claims 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 9, 2026.
Drawings
The drawings are objected to because the dimensions marked in white on Figure 1 are barely visible. The dimension marking on the right edge of the figure (approximately mid-way up) is cut off. 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.
Claim Objections
Claims 1 and 20 are objected to because of the following informalities:
the “/or” should be removed in “selected from an inhibitor of poly ADP… and/or a Toll-like receptor (TLR) agonist”;
“[P]oly ADP ribose polymerase” is conventionally denoted “poly (ADP-ribose) polymerase”; and
some punctuation, line break, and/or indentation should precede the “wherein…” clause.
Claim 2 is objected to because of the following informalities: lack of antecedent basis for “the particles”.
Claims 10 and 11 are objected to because of the following informalities: lack of a hyphen in “acid terminated” and “ester terminated”.
Appropriate corrections are required.
Claim Rejections - 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 1-16 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 1 and 20 recite “wherein (a) 50% of a total amount of the immunotherapeutic agent in the biodegradable polymeric microspheres is released from the biodegradable polymeric microspheres into a 37° C solution of PBS Tween 20 (0.05%) at a point in time between 3 days and 14 days; (b) between 1 mg and 100 mg of immunotherapeutic agent per 1 g dry weight of microspheres is released from the biodegradable polymeric microspheres into a 37° C solution of PBS Tween 20 (0.05%) at a point in time between 3 days and 14 days; or (c) both (a) and (b)”. The specification does not adequately describe an adequately representative number of biodegradable polymeric microspheres comprising a biodegradable polymer and an immunotherapeutic agent selected from a PARP inhibitor and a TLR agonist.
The methodology for determining adequacy of written description entails (1) for each claim, determining what the claim as a whole covers, (2) reviewing the entire application to understand how applicant provides support for the claimed invention including each element and/or step, and (3) determining whether there is sufficient written description to inform a skilled artisan that applicant was in possession of the claimed invention as a whole at the time the application was filed. MPEP §2163(II). Also the “written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice …, reduction to drawings …, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” MPEP §2163(II)(A)(3)(a)(ii) (citations omitted). The “Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 ‘merely by clearly describing one embodiment of the thing claimed’.” Id. (citations omitted).
1) Claim 1 as a whole covers any biodegradable polymeric microspheres comprising any biodegradable polymer at any concentration, and an immunotherapeutic agent selected from any PARP inhibitor and any TLR agonist, at any concentration, wherein biodegradable polymeric microspheres in any size exhibit one or both of a release profile between 3 and 14 days, determined by the active agent weight concentration or quantity. Claim 20 recites a kit comprising the biodegradable polymeric microspheres of claim 1 and a device such as a vial, needle, and so on. Only claim 3 recites the concentration of the PARP inhibitor or the TLR agonist as “between 3wt% and 10 wt%”; however claim 3 does not specify any other parameters of the biodegradable polymeric microspheres, e.g., excipients and their concentration in the microspheres and the biodegradable polymer used.
(2) The entire application has been reviewed to understand support for the claimed invention including each element. The disclosure (paras.[0053]-[0062]) teaches microspheres made from four PLGA’s of Resomer® brand, all four comprising 50:50 lactide:glycolide ratio. Three of the Resomer® PLGA’s comprised identical Mw 7-17k, and Resomer®501H had a lesser molecular weight indicated by inherent viscosity. Three PLGA’s were acid-terminated, and only RG502 was ester-terminated. Active agents were either milled imiquimod or milled olaparib. The microspheres were made via oil-in-emulsion technique using polyvinyl alcohol in water, followed by filtration to specific size ranges, and lyophilization. Figure 2 shows the percent release of active agent from the four microsphere types disclosed; however it shows only three of the four embodiments. All three comprised acid-terminated PLGA with lactide:glycolide ratio of 50:50. Therefore there is no disclosure of whether the ester-terminated PLGA attained the recited release profile. Also there is no discussion or contemplation of how different PARP inhibitors or different TLR agonists, or lack of a milling step for the active agent, different biodegradable polymers and processing steps, size of the microspheres, and other factors could affect the release profiles of each type of microspheres. Therefore this is an instance wherein “a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 ‘merely by clearly describing one embodiment of the thing claimed’.” MPEP §2163(II)(A)(3)(a)(ii) (citations omitted). The breadth of disclosure as compared to the scope of the claims at hand does not indicate possession of the claimed genus.
(3) Therefore it is determined that there is not sufficient written description to inform a skilled artisan that applicant was in possession of the claimed invention as a whole at the time the application was filed.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4-9, 12-16, and 20 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Heit (Heit, A., et al., Antigen co-encapsulated with adjuvants efficiently drive protective T cell immunity, Eur. J. Immunol. 2007, 37:2063-74).
Heit teaches “biodegradable poly(lactic-co-glycolic) microspheres (MP) co-entrapping Ag [antigen] and Toll-like receptor (TLR) 9 or 7 ligands as an endosomal delivery device” (abstract; pp.2066-72). “[T]he microparticles were generated by emulsifying 200 mg polymer(PLG Resomer 502, 50:50 lactide:glycolide ratio,…)” (p.2071 rt. col.). “The particle size ranged from 1–30 µm” (p.2072 left col.), i.e., 30 µm in instant claim 4. Resomer® 502 is an ester-terminated PLGA. “MP-based vaccination not only protected towards otherwise lethal infections, but also exerted protective and therapeutic effects towards mouse melanoma tumor cells.” (p.2064 rt col.; see p. 2065 left col.). The MPs are prepared in a process comprising lyophilization or freeze drying, prior to being formulated in PBS for injection (p.2072 left col.). Official notice is taken that injectable formulations are commonly provided in a vial for dispensing into a syringe.
Regarding the active agent release profile between 3 days and 14 days in the “wherein” clauses of claims 1 and 20, Heit does not expressly discuss a release rate of the TLR ligands CpG-ODN (CpG- oligodeoxynucleotides) or R837 from its microspheres in PBS Tween 20 as recited. However endosomal release of encapsulated ligand as verified by “large amounts of IL-12 and IL-6” production (p.2065 left col.; see Fig.1, 4, 5 and accompanying text). Furthermore Heit’s microspheres anticipate claims 1 and 20 by teaching all the structural features of claims 1 and 20: “[b]iodegradable polymeric microspheres comprising a biodegradable polymer and an immunotherapeutic agent selected from … a Toll-like receptor (TLR) agonist”. A “chemical composition and its properties are inseparable”. MPEP § 2112.01(II). For product claims, “when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent”. MPEP §2112.01(I). Furthermore “[s]omething which is old does not become patentable upon the discovery of a new property… [T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer…. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.” MPEP §2112(I)(citations omitted). Thus Heit’s microspheres are presumed to inherently comprise the active agent release profile between 3 days and 14 days in the “wherein” clause of claims 1 and 20. Furthermore discovery of the release profile does not render Heit’s microspheres patentable to Applicant.
Claim(s) 1, 3-10, 12-16, and 20 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being clearly anticipated by Wang (US 2022/0040310).
Wang teaches Toll-like receptor (TLR) agonists including comprising-ODN (CpG oligodeoxynucleotide), polyinosinic:polycytidylic acid (poly IC), R837, and imiquimod, embedded in injectable PLGA microparticles of up to 100 µm (para.0039), including “1-30 µm in diameter” (para.0101; see title; abstract; paras.0004, 0074, 0101, 0228 ; claims 1-10). In one embodiment “PLGA microparticle (5 μm-20 μm) contains 3% polyIC, 1% imiquimod, 5% paclitaxel,…” (para.0229). Wang teaches using acid-terminated 50:50 PLGA to form microparticles (paras.0101, 0104-05). Wang teaches both lyophilized or injectable formulation in a buffer (paras.0039-40). Official notice is taken that injectable formulations are commonly provided in a vial for dispensing into a syringe.
Regarding the active agent release profile between 3 days and 14 days in the “wherein” clauses of claims 1 and 20, Wang does not expressly discuss a release rate of the TLR ligands from its microspheres in PBS Tween 20 as recited. However endosomal release of encapsulated ligand as verified by “large amounts of IL-12 and IL-6” production (p.2065 left col.; see Fig.1, 4, 5 and accompanying text). Furthermore Wang’s microparticles anticipate claims 1 and 20 by teaching all the structural features of claims 1 and 20: “[b]iodegradable polymeric microspheres comprising a biodegradable polymer and an immunotherapeutic agent selected from … a Toll-like receptor (TLR) agonist”. A “chemical composition and its properties are inseparable”. MPEP § 2112.01(II). For product claims, “when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent”. MPEP §2112.01(I). Furthermore “[s]omething which is old does not become patentable upon the discovery of a new property… [T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer…. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.” MPEP §2112(I)(citations omitted). Thus Wang’s microparticles are presumed to inherently comprise the active agent release profile between 3 days and 14 days in the “wherein” clause of claims 1 and 20. Furthermore discovery of the release profile does not render Wang’s microspheres patentable to Applicant.
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.
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.
Claim(s) 1-16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US 2022/0040310 ).
Wang does not specifically teach using TLR agonists in the form of nanoparticles as recited in claim 2 or using both an acid-terminated and ester-terminated PLGA to form microparticles as in claim 11. However it would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to do so. The skilled person would have been motivated to do so because Wang teaches milling water insoluble drugs such as imiquimod (para.0096), and preparing nanosized PLGA particles, i.e., nanoparticles, which contain the agonists therein. The drug particles contained therein would be smaller and thus nanoscale. Furthermore the selection of a known material or mechanism based on its suitability for its intended use supports a prima facie obviousness determination. MPEP §2144.07 (citations omitted). Here although Wang does not teach a micron-scale PLGA particle comprising both acid-terminated and ester-terminated PLGA as in claim 11, Wang teaches nanoparticles comprising both “PLGA (50:50 glycolide/lactide, MW=17000) with terminal COOH groups and 500 mg of PLGA-NHS (PLGA-N-hydroxysuccinimide, MW 50,000-80,000 Da, LA:GA 50:50)” and the TLR agonist R837 (para.0104). Wang does not limit the use of the combination to nanoparticles. The skilled person would have understood that the same may be used to form microparticles.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614
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