DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
In the Preliminary Amendment filed 02 April 2024, Applicant amended claims 3-14 and 16-20. Claims 1-20 are pending.
Warning: Duplicate Claims
Applicant is advised that should claim 11 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. MPEP § 608.01(m).
Claim Rejections - 35 U.S.C. 102(a)
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102(a) that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless
(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; or
(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.
Claims 1, 3, 5-8, and 10-13 are rejected under 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) as being anticipated by Fakhari (WO 2018/049017 A1), as evidenced by Wang (“Modified PLGA–PEG–PLGA thermosensitive hydrogels with suitable thermosensitivity and properties for use in a drug delivery system.” Journal of materials chemistry B 5.8 (2017): 1551-1565) and Patinote (“Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes.” European journal of medicinal chemistry 193 (2020): 112238).
Fakhari is directed to “[b]lock copolymer systems for local administration of toll-like receptor agonists.” Title.
Fakhari discloses: “Provided are compositions comprising a reverse thermosensitive polymer, an immune response modifier (IRM), and ethanol. In certain aspects, the reverse thermosensitive polymer is polyoxamer 407 or PLGA-PEG-PLGA. The IRM can be a Toll-like receptor (TLR) agonist, in particular, a TLR7, TLR8, or TLR7/8 agonist.” Abstract.
Fakhari discloses that “Poly(lactic-co-glycolic acid)-b-Poly(ethylene glycol)-b-Poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer (Mn: 1,600: 1,500: 1,600 Da, 3:1 LA:GA) was acquired from PolySciTech (West Lafayette, IN)” was selected as the block copolymer. Page 25; see also page 32. That PLGA-PEG-PLGA has a “sol-gel transition around 37°C.” Page 32 at para. [00147]; see also page 33 at Table 6 (showing comparable sol-gel transition temperatures for the formulation). As evidenced by page 1551 (right column) of Wang, PLGA–PEG–PLGA copolymers form micelle structures in aqueous solution.
Fakhari discloses that the following TLR 7/8 agonists were used to prepare the formulations: S-36878 and S-36862. Page 32. As stated on page 8 (para. [0027]) of Fakhari, FIG. 2A shows the structure of the TLR 7/8 agonist S-36878 (non-lipidated), and FIG. 2B shows the structure of the TLR 7/8 agonist S-36862 (lipidated). Both those figures are reproduced below:
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The TLR agonist shown in Figure 2B is Telratolimod (3M-052, MEDI-9197), as evidenced by Figure 23 of Patinote (page 15). This observation is relevant because Telratolimod is defined as a hydrophobic immunoadjuvant in claim 10 of the present application.
The combination of PLGA-PEG-PLGA and Telratolimod is also disclosed in claim 4 of Fakhari (page 42).
Fakhari discloses that “[b]y mixing the drug solution to the excipient solution, particles of the drug form within excipient solution in-situ (FIG. 19)” (page 33), thereby evidencing encapsulation of the Telratolimod.
Fakhari discloses that the Telratolimod/PLGA-PEG-PLGA formulation is injectable. Pages 33-34 at paras. [00150]-[00151] and Table 7. Additionally, that formulation is configured for intratumoral (IT) injection. Fakhari, page 36, at para. [00159] and Table 9.
Claims 11-12 of Fakhari (page 43) disclose that the PLGA-PEG-PLGA formulation is capable of encapsulating 1 mg/ml of Telratolimod (S-36862). See also page 6 at para. [0016] (“In some instances, the composition can comprise 0.05 to 1.3 mg/mL IRM. For example, the concentration of IRM can be selected from the group consisting of 0.08 mg/mL, 0.4 mg/mL, and 1 mg/mL”).
Fakhari discloses that the Telratolimod/PLGA-PEG-PLGA formulation satisfies the extended-release profile recited at the end of Applicant’s claim 1. Figure 25B; see also page 35 at Example 5.
The presence of a radio-opaque label is not required to satisfy claims 1 and 3 because the corresponding concentration ranges include 0 mg/ml. MPEP § 2111 (“During patent examination, the pending claims must be ‘given their broadest reasonable interpretation consistent with the specification.’”).
In sum, claims 1, 3, 6-7, and 10-13 are anticipated by Fakhari.
Regarding claim 5, Applicant is alerted that “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).
Regarding claim 8, Telratolimod has a molecular weight of approximately 593.9 Daltons and, therefore, qualifies as “small” in accordance with page 17, lines 19-26, of Applicant’s specification, as originally filed.
Claim Rejections - 35 U.S.C. 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 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(a) 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.
Claims 2, 4, and 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Fakhari (WO 2018/049017 A1), as applied above in the §102(a) rejection of claims 1, 3, 5-8 and 10-13, in view of Som (“Image-guided intratumoral immunotherapy: Developing a clinically practical technology.” Advanced drug delivery reviews 189 (2022): 114505), as evidenced by Knavel (“Tumor ablation: common modalities and general practices.” Techniques in vascular and interventional radiology 16.4 (2013): 192-200).
Fakhari is discussed above, in the rejection under 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2). That discussion is incorporated by reference into this §103 rejection.
Although Fakhari discloses intratumoral injection, Fakhari is silent as to whether a radio-opaque agent can be included in the PLGA-PEG-PLGA/TLR agonist formulations disclosed therein. Consequently, Fakhari does not satisfy claims 2, 4, and 14.
Fakhari is also silent regard CT imaging, which is required by claim 15.
As explained below, the following reference compensates for this deficiency: Som.
Som teaches: “Effective intratumoral injections require precise delivery of the drug into the target lesion and may also depend on the distribution of the drug throughout tumor.” Page 3, right column.
Som teaches: “While superficial lesions can be injected by visual inspection, the majority of lesions are non-palpable and require image guidance for injection in the interventional radiology suite. The mostly widely utilized imaging modalities for intratumoral injection are computed tomography (CT) and ultrasound, with ultrasound being favored for anything <5 cm deep, including subcutaneous, thyroid, or breast lesions, and CT for deeper lesions and those in visceral organs. The technique for a CT or ultrasound-guided therapeutic injection is similar to that of biopsy, which is routinely performed and accurate within a few mm of the target virtually anywhere in the body. Imaging is used to guide needle placement into tumor, but the distribution of injected intratumoral therapy within (or outside of) tumor is often unevaluable since the therapy itself cannot by visualized by the imaging modality.” Page 3, right column.
Som teaches: “Iodinated contrast is the mainstay for increased contrast visualization particularly to look at enhancement of lesions. Concentrations for radio-opacity are typically in the 100 mgI/mL range and can be mixed in at 10–50% v/v intravenously.” Pages 11-12 (bridging sentence).
In Table 3 (page 13), Som teaches that iodinated contrast agents can be included in PLGA-PEG-PLGA injectable formulations. See also page 14 at Section 4 (amphiphilic block-polymers that self-assemble into nanoparticles allow for the solubilization of hydrophobic compounds and encapsulation of imaging agents).
Before the effective filing date of the claimed invention, a person having ordinary skill in the art would have been motivated by the teachings of Som to include an iodinated contrast agent (a radio-opaque agent) in the PLGA-PEG-PLGA/TLR agonist formulations of Fakhari to advantageously allow for CT imaging/monitoring during intratumoral therapy. Therefore, claims 2, 4, 14-15, and 17-20 are prima facie obvious. MPEP § 2144.05(I) (obviousness of similar and overlapping ranges, amounts, and proportions) and, alternatively, MPEP § 2144.05(II)(A) (“Generally, differences in concentration or temperature will not support the patentability ofsubject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”).
Regarding claim 16, Som teaches “thermal ablation” to treat tumors (page 10, right column). As evidenced by Knavel, there are only two types of thermal ablation. See Abstract (“During tumor ablation, thermal energy is used to heat or cool tissue to cytotoxic levels (less than -40°C or more than 60°C).”). Accordingly, a person having ordinary skill in the art would have readily envisaged cryoablation.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Fakhari (WO 2018/049017 A1), as applied above in the §102(a) rejection of claims 1, 3, 5-8 and 10-13, in view of Patinote (“Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes.” European journal of medicinal chemistry 193 (2020): 112238).
Fakhari is discussed above, in the rejection under 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2). That discussion is incorporated by reference into this §103 rejection.
Although Fakhari discloses that Telratolimod can be selected as the TLR7/8 agonist for the PLGA-PEG-PLGA formulation, Fakhari is silent as to whether any of the compounds recited in claim 9 can be selected instead, all of which are TLR7, TLR8, or TL7/8 agonists. As explained below, Patinote compensates for this deficiency.
Patinote is directed to agonists and antagonists of TLRs 7/8.
Patinote teaches the chemical structure of resiquimod in Figure 20 (page 13), which is shown below:
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Patinote teaches that (i) resiquimod is a TLR7/8 agonist; (ii) has an antitumor effect against skin cancer; and (iii) has proven to be an effective adjuvant against several diseases as cancer given its ability to induce local activation of immune cells. Page 14.
Before the effective filing date of the claimed invention, it would have been obvious to a person having ordinary skill in the art — following a review of Patinote — to modify Fakhari by substituting resiquimod for Telratolimod, given their similar chemical structures and similar utilities. Therefore, claim 9 is prima facie obvious. MPEP § 2144.09(I) (“A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.”); see also MPEP § 2144.06(II) (substituting equivalents known for the same purpose).
Conclusion
Claims 1-20 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
04 April 2026
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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