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 .
Status of Claims
The amendment filed on 04/22/2026 is acknowledged.
Claims 3, 5, 8-10, 12-17, 20, 21, 23, 24, 28, 29, 34-36, 39 and 41 are canceled.
Claims 2, 4, 6, 7, 11, 18, 19, 22, 25, 27, 30, 31, 32, 33, 37, 38, 40 are amended.
Claims 1-2, 4, 6, 7, 11, 18, 19, 22, 25-27, 30-33, 37, 38, 40 and 42 are pending and under consideration.
Information Disclosure Statement
The information Disclosure statements (IDS) filed on 02/05/2024, 11/18/2024, 01/17/2025, 02/24/2025, 08/01/2025, 09/16/2025, 11/19/2025 and 04/22/2026 are considered, initialed and are attached hereto.
Priority
Applicant’s claim for benefit of U.S. provisional application 63/143,936, filed January 30, 2021, is acknowledged.
Election/Restriction
Applicant’s election without traverse of (a) a biomaterial preparation and at least one immunomodulatory payload; (b) a TLR7/8 agonist; and (c) a modulator of innate immunity, filed on April 22, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s comments regarding examination to be extended to the additional species upon allowance of a genetic claim are noted.
Specification
The use of the term SynperonicsTM, Pluronic®, Kolliphor®, which is a trade name or a mark used in commerce, has been noted in this application. 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.
The data and examples in the specification are not completely clear. There are a lot of “embodiments” in the example section and it is not immediately apparent what has actually been carried out (e.g. where exactly the biomaterial has been placed). It is assumed that the lymph node resection site is different from the tumor resection site in the examples. The applicant should clarify the exact methods used in the examples.
Claim Interpretation
The specification teaches the term “a lymph node dissection site” means one or more lymph nodes is partially or fully removed from a subject who is suspected of or known to be suffering from cancer (paragraph [000103]). Therefore, the lymph node dissection site is interpreted to include 1) a lymph node that is partially removed (for instance for biopsy), 2) multiple lymph nodes that are partially removed, 3) a lymph node that is completely removed, and 4) multiple lymph nodes are completely removed. In addition, since the claim does not specify if the lymph node dissection is required to be performed before, at the same time with, or after the claimed step of administering the immunomodulatory composition, the claim is interpreted as encompassing all three options.
Claim Rejections
Claim 11 is objected to for using the acronym “TLR7/8” without defining its proper name at its first occurrence in the claims.
Claim Rejections - 35 USC § 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.
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 2, 25-26, 32 and 42 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.
a. The phrase “characterized by” in claim 2 renders the claim indefinite because its meaning is unclear. The specification fails to explain the term.
b. The phrase “at least a portion” in claims 25-26 renders the claims indefinite because it is unclear what amount is considered “a portion”. The specification fail to specify if it is 0.1%, or 99%. Therefore, the boundaries of the claims become subjective.
c. Regarding claim 32, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Specifically, applicants use “e.g.” in reference to a gastrointestinal track cancer, whereby the language “e.g.” identifies species (a stomach cancer) of a gastrointestinal track cancer. It is unclear if the gastrointestinal track cancer is required to be stomach cancer or encompasses species beyond the stomach cancer, such as liver cancer or pancreatic cancer. As the metes and bounds of the claim limitation are unclear, the claim is rejected for indefiniteness.
d. Claim 42 recites the limitation "the improvement" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Written Description
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 1-2, 4, 6, 7, 11, 18, 19, 22, 25-27, 30-33, 37, 38, 40 and 42 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicant are claiming and what Applicant have possession of.
The claims are drawn to a method of treating cancer, comprising a step of administering to a target site in a cancer subject, a composition comprising an immunomodulatory composition, wherein the target site is or comprises a lymph node dissection site.
The specification teaches the term “cancer” feres to a malignant neoplasm and includes many different types of cancers (instant specification paragraph [00036]).
The specification states a TLR7/8 agonist, it is an agonist for both Toll-like receptor 7 and 8 (instant specification paragraphs [000190]). This is a functional statement and a TLR7/8 agonist could be any molecules, such as fusion proteins, antibody-drug conjugates and small molecules.
Therefore, the claims recite administering a composition comprising a genus of TLR7/8 agonists to treat all types of cancers.
Regarding to using a TLR7/8 agonist to treat all types of cancers, the specification has written description of the following example: after the proximal lymph node resection in a 4T1-Luc2 breast cancer mouse model, administering a biomaterial preparation that comprises R848 (resiquimod) that is or includes the lymph node resection site, lead to prolonged animal survival compared with empty biomaterial as a negative control (examples 1-3). However, the specification does not have written description for using a TLR7/8 agonist to treat all types of cancers.
In the state of the art, the effect of a TLR7/8 agonist against different types of cancers are not predictable. For instance, Maddineni et al (Cancers 2023, 15 (17), 4386) reviews the various TLR agonists in head and neck squamous cell carcinoma (HMSCC) in clinical trials, and concludes that TLR agonists, including NKTR-262 (a TLR7/8 agonist), do not appear to provide benefits to this type of cancer (whole document). Kumar et al (Journal of Gynecological Cancer. Volume 23, Issue 1, 2013, Pages 184-192) teaches human cervical cancer Langerhans cells are functionally anergic to TLR7 and TLR8 ligands (see Conclusions), suggesting the cancer is unlikely to respond to TLR7/8 agonists. Sun et al (Biomark Res. 2022 Dec 7;10(1):89.) teaches while R848 treated mice demonstrated survival benefits, the expression of TLR7/TLR8 is increased in stage I-IV pancreatic cancer in a state-dependent manner in advanced tumors and stimulation of TLR7/TLR8 expression by R848 results in increased cancer cell proliferation and reduced chemosensitivity (see section Pancreatic cancer). Siu et al (J Immunother Cancer. 2020. Oct;8(2):e001095) teaches intertumoral administration of MEDI9197 (a TLR7/8 agonist) in patients with advance solid tumors, appeared feasible for cutaneous and subcutaneous, but challenging for deep-seated lesion, and no patients responded despite local and systemic immune activation is observed (whole document). Bhagchandani (Adv Drug Deliv Rev. 2021 Aug;175:113803) teaches in a A20 B cell lymphoma mouse model, R848, as a monotherapy, has limited effect in tumor inhibition and mouse survival (Figure 8C).
Therefore, the state of the art support that not all cancers can be treated with a TLR7/8 agonist.
Regarding the TLR7/8 agonist, although the claims are inclusive of one TLR7/8 agonist (R848), they claims also broadly encompass all TLR7/8 agonists, such as fusion proteins, antibody-drug conjugates and small molecules. Therefore, these structures are claimed only by their functional characteristics and the specification fails to provide sufficient correlation between the claimed functional characteristics and the necessary structural components.
In the state of the art, it is impossible for one of skill in the art to predict if a certain molecule would function to inhibit a particular protein. Due to the structure difference between species, TLR7 and TLR8 might respond to the same agonist differently between species. In other words, while one agonist is a TLR7/8 agonist in one species, it might be agonist for only one receptor in another species. For instance, Zhu et al (Molecular Immunology, 2008, volume 45, issue 11, page 3238-3243) teaches human and mouse TLR7 and TLR8 show different receptor specificity to both synthetic and physiological ligands, such as resiquimod and ssRNA (Introduction). In addition, imiquimod, a selective TLR7 ligand for mouse and human, activates both porcine TLR7 and TLR8 (Abstract, Section 3.2). BenchChem Technical Support Team (Foundational and Exploratory, 2026 April) teaches CL075 is a TLR7/8 agonist for human but it does not activate mouse TLR8 (section Core Differences in Receptor Activation and Cellular Response). However in the rabbit, CL075 activates TLR8 mildly but not TLR7 (Lai et al, Vaccine. Volume 32, Issue 43, 2014. Pages 5593-5599).
Second, the effect of different TLR7/8 agonists in cancer treatment is unpredictable. For instance, Mullins et al (J. immunotherapy cancer (2019) 7, 244) teaches when administered intratumorally, MEDI9197 is able to inhibit tumor growth and enhance long-term survival in mice bearing established B16-OVA melanoma tumors, but not resiquimod (section MEDI9197 induces a range of immunological changes within the tumor microenvironment (TME) resulting in anti-tumor efficacy). Zuniga et al (Cancer Cell Int. 2022 Sep 19;22(1):286) teaches intratumoral delivery of TLR agonists generally lead to rapid effusion of the compound from the injection site, which necessitates frequent dosing regimens, leading to undesired systemic proinflammatory cytokine induction (section Background). In a CT26 mouse tumor model, intratumoral injection of resiquimod does not provide significant anti-tumor activity, while TransCon TLR7/8 agonist, which is a sustained-release prodrug of resiquimod, show potent and sustained anti-tumor benefits (page 5 left column, page 6 left column).
The specification does not provide adequate written description to identify the broad and variable genus of the TLR7/8 agonists because, inter alia, the specification does not disclose a correlation between the necessary structure and the function(s) recited in the claims. A definition by function does not suffice to define the genus because it is only an indication of what the molecule does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves that result. In addition, given the highly diverse nature of the claimed genus of molecules, even one of skill in the art cannot envision the structure of the agonists by its functional characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of molecules claimed only by a functional characteristic.
Furthermore, Applicant has not shown procession of a representative number of species that have the claimed function(s). The specification has written description for the examples: after the proximal lymph node resection in a 4T1-Luc2 breast cancer mouse model, administering a biomaterial preparation that comprises R848 (resiquimod) that is or includes the lymph node resection site, lead to prolonged animal survival compared with empty biomaterial as a negative control (examples 1-3). However, as noted above, the claims are not limited to this one exemplary molecule, and encompass any molecule that is an agonist of TLR7/8. There is no description of the structure common to the members of the genus that one of skill in the art can visualize or recognize the members of the genus. Therefore, only one species have been described and this is not considered to be representative of the breadth of the genus. Given the lack of structure function correlation and the lack of a representative number of species, the specification provides insufficient written description to support the genus encompassed by the claim.
Taken together, neither the state of the art or the specification provides a sufficient representative number of species to meet the written description requirement for using a genus of TLR7/8 agonists to treat all types of cancers.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The skilled artisan cannot envision the detailed chemical structure of the encompassed molecules of TLR7/8 agonists. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
In Abbvie v. Centocor (Fed. Cir. 2014), the Court noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
The instant case has many similarities to Abbvie above. First, the claims clearly attempt to define the genus of TLR7/8 agonists by the functions. As noted by Abbvie above, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description. Second, there is no information in the specification based upon which one of skill in the art would conclude that the disclosed single example would be representative of the entire genus. The specification discloses no structure to correlate with the function.
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function (see MPEP 2163). A patent specification must set forth enough detail to allow a person of ordinary skill in the art to understand what is claimed and to recognize that the inventor invented what is claimed. In the case of DNA, an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention (see Lilly, 119 F.3d at 1566 (quoting Fiers, 984 F.2d 15 1171). Because the specification does not describe the structures for potentially numerous TLR7/8 agonists, which would have the recited functions, one of skill in the art would reasonably conclude that applicant was not in possession of a method of treating all types of cancers comprising administering a composition comprising any TLR7/8 agonists.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, there is not identification of any particular portion of the structure that must be conserved or present. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Enablement
Claims 1-2, 4, 6, 7, 11, 18, 19, 22, 25-27, 30-33, 37, 38, 40 and 42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating mouse 4T1-luc2 cancer by administering a composition comprising R848 to the target site, does not reasonably provide enablement for treating any type of cancers with any TLR7, TLR8, or TLR7 and 8 agonists. The specification is not enabling to use any types of TLR7/8 agonist to treat all types of cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
It is noted that MPEP 2164.03 teaches that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order to be enabling.”
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)):
1) nature of the invention;
2) the breadth of the claims;
3) the state of the prior art;
4) the level of one of ordinary skill;
5) the level of predictability in the art;
6) the amount of direction or guidance provided by the inventor;
7) the existence of working examples; and
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (2) The breadth of the claims
The claims are drawn to a method of treating cancer comprising a step of administering to a target site in a cancer subject, a composition comprising an effective amount of an immunomodulatory composition, wherein the target site is or comprises a lymph node dissection site.
Regarding cancer, there are hundreds of cancers, which have in common only some loss of controlled cell growth. The specification is enabling for one specific example, which is a mouse 4T1-Luc2 breast cancer model (examples 1-3). The specification does not have enablement for using a TLR7/8 agonist to treat all types of cancer.
Regarding TLR7/8 agonists, there are unlimited number of TLR7/8 agonists. The specification is enabling for using one specific TLR7/8 agonist, R848 (resiquimod), to treat cancer (examples 1-3). The specification does not have enablement for using any TLR7/8 agonists in the claimed method.
(3) The state of the prior art and (5) The level of predictability of the art
Regarding treating all types of cancer, while the state of the art is relatively high with regard to the treatment of specific tumor types with specific reagents, the state of the art with regard to treating cancer broadly is underdeveloped. In particular, there is no known anti-cancer agent that is effective against all cancer types. The cancer treatment art involves a very high level of unpredictability. The lack of significant guidance from the present specification or prior art with regard to the actual treatment of all cancers with any TLR7/8 agonist makes practicing the claimed invention unpredictable.
Cancers arising from different tissues differ in etiology and response to treatment. Heppner et al (Cancer Metastasis Review 2:5-23; 1983) discuss the heterogeneity of tumors from different tissues, as well as the same tissue, and tumor heterogeneity contributes greatly to the sensitivity of tumors to drugs. Heppner et al. teach that as a tumor progresses to a metastatic phenotype, the susceptibility to a particular treatment can differ, and as such, makes predicting the responsiveness to treatment difficult.
With regard to cancer treatment, Bally et al. (US 5,595,756) teaches although a number of bioactive agents have been found to be effective against cancer cells, the clinical use of such anti-cancer agents has been highly compromised because of treatment-limiting toxicities (Bally et al. col. 1, lines 17-24).
Sporn et al (“Chemoprevention of Cancer,” Carcinogenesis, Vol. 21 (2000), 525-530) teaches the magnitude of mortality of cancers and that new approaches to a variety of different cancer are critically needed. Sporn et al also teaches because the genotype and phenotype heterogeneity in advanced malignant lesions in individual patients, it is hard to know the specific molecular and cellular targets a potential therapy should target.
Furthermore, the art indicates the difficulties in going from animal model to clinical studies for drug development for treatment of cancers. Gura T (Science, 1997, 278(5340): 1041-1042, encloses 1-5) indicates that the model systems used in cancer drug discovery are not predictive at all (see p. 1, 2nd paragraph). Gura T also teaches that the results of xenograft screening might not be much better than those obtained with the original models, mainly because the xenograft rumors do not behave like naturally occurring tumors in humans (see p. 2, 4th paragraph).
The gene and/protein difference between species also makes it difficult to develop and translate compounds across species. For instance, TLR8 has species-specific structure that is essential for species-specific ligand recognition (Liu et al. Mol Immunol. 2010 Feb; 47(5): 1083-90). Therefore, an agonist that can bind with human TLR8 might not bind with mouse TLR8.
Hait (Nature Reviews/Drug Discovery, 2010, 9, pages 253-254) states that “data suggest that the overall success rate for oncology products in clinical development is -10%” (see page 253, left column, the 1st paragraph). Hait further teaches several reasons why the outcome for a particular cancer target may be disappointing, such as incomplete understanding of the target in the pathogenesis of specific human malignancies, the putative role of cancer stem cells in limiting the efficacy of cancer therapeutics, the roles of single nucleotide polymorphisms in genes responsible for drug metabolism by affecting drug pharmacokinetics (page 253, Section “Understanding the target in context).
Hait also teaches drug effects in preclinical cancer models often do not predict clinical results. Despite several improvements have been made, including orthotopic implantation and use of mice with humanized hematopoietic and immune systems and newer genetic mouse models, whether or not these models will more accurately predict drug activity against human cancer remains to be determined. Other alternatives, including three-dimensional tissue culture or xenografts of fresh human biopsy specimens onto immunocompromised mice, have the potential advantage of including the human microenvironment. However, these approaches have yet to prove their value relative to their cost (page 253, Section “Predictive models).
The challenges facing cancer drug development are further confirmed and discussed in Gravanis et al (Chin Clin Oncol, 2014, 3(2):22, pages 1 -5). Gravanis et al. teaches the constantly evolving biology of the tumor may be to blame for the frequent non-reproducibility of research results, systemic biology approaches of the -omic type still generate largely incomprehensible, and animal models of cancer are similarly unable to predict the clinical situation (page 3, right column, the 2nd paragraph).
In addition, the effect of a TLR7/8 agonist against different types of cancers are not predictable. Maddineni et al (Cancers 2023, 15 (17), 4386) reviews the various TLR agonists in head and neck squamous cell carcinoma (HMSCC) in clinical trials, and concludes that TLR agonists, including NKTR-262 (a TLR7/8 agonist), do not appear to provide benefits to this type of cancer (whole document). Kumar et al (Journal of Gynecological Cancer. Volume 23, Issue 1, 2013, Pages 184-192) teaches human cervical cancer Langerhans cells are functionally anergic to TLR7 and TLR8 ligands (see Conclusions), suggesting the cancer is unlikely to respond to TLR7/8 agonists. Sun et al (Biomark Res. 2022 Dec 7;10(1):89.) teaches while R848 treated mice demonstrated survival benefits, the expression of TLR7/TLR8 is increased in stage I-IV pancreatic cancer in a state-dependent manner in advanced tumors and stimulation of TLR7/TLR8 expression by R848 results in increased cancer cell proliferation and reduced chemosensitivity (see section Pancreatic cancer). Siu et al (J Immunother Cancer. 2020. Oct;8(2):e001095) teaches intertumoral administration of MEDI9197 (a TLR7/8 agonist) in patients with advance solid tumors, appeared feasible for cutaneous and subcutaneous, but challenging for deep-seated lesion, and no patients responded despite local and systemic immune activation is observed (whole document). Bhagchandani (Adv Drug Deliv Rev. 2021 Aug;175:113803) teaches in a A20 B cell lymphoma mouse model, R848, as a monotherapy, has limited effect in tumor inhibition and mouse survival (Figure 8C).
Given Bally et al. teaching of treatment-limiting toxicities in clinical use; Sporn's teaching that the cancer progression is heterogeneous as it progresses, both in genotype and phenotype; Gura's and Liu’s teaching that the models are unpredictable; both Hait and Gravanis et al teaching various challenges facing cancer drug development, such as an understanding of cancer biology is far from complete, drug effects in preclinical cancer models often do not predict clinical results and many others; Maddineni et al, Kumar et al, Sun et al, Siu et al and Bhagchandani et al’s teaching that the effect of a TLR7/8 agonist can be used to treat all types of cancer, the cited references demonstrate that treatment of all types of cancer using aTLR7/8 agonist is not predictable.
Regarding the TLR7/8 agonists, its effect is also not predictable.
First, it is impossible for one of skill in the art to predict if a certain molecule would function to inhibit a particular protein. Due to the structure difference between species, TLR7 and TLR8 might respond to the same agonist differently between species. In other words, while one agonist is a TLR7/8 agonist in one species, it might be agonist for only one receptor in another species. For instance, Zhu et al (Molecular Immunology, 2008, volume 45, issue 11, page 3238-3243) teaches human and mouse TLR7 and TLR8 show different receptor specificity to both synthetic and physiological ligands, such as resiquimod and ssRNA (Introduction). In addition, imiquimod, a selective TLR7 ligand for mouse and human, activates both porcine TLR7 and TLR8 (Abstract, Section 3.2). BenchChem Technical Support Team (Foundational and Exploratory, 2026 April) teaches CL075 is a TLR7/8 agonist for human but it does not activate mouse TLR8 (section Core Differences in Receptor Activation and Cellular Response). However in the rabbit, CL075 activates TLR8 mildly but not TLR7 (Lai et al, Vaccine. Volume 32, Issue 43, 2014. Pages 5593-5599).
Second, the effect of different TLR7/8 agonists in cancer treatment is unpredictable. For instance, Mullins et al (J. immunotherapy cancer (2019) 7, 244) teaches when administered intratumorally, MEDI9197 is able to inhibit tumor growth and enhance long-term survival in mice bearing established B16-OVA melanoma tumors, but not resiquimod (section MEDI9197 induces a range of immunological changes within the tumor microenvironment (TME) resulting in anti-tumor efficacy). Zuniga et al (Cancer Cell Int. 2022 Sep 19;22(1):286) teaches intratumoral delivery of TLR agonists generally lead to rapid effusion of the compound from the injection site, which necessitates frequent dosing regimens, leading to undesired systemic proinflammatory cytokine induction (section Background). In a CT26 mouse tumor model, intratumoral injection of resiquimod does not provide significant anti-tumor activity, while TransCon TLR7/8 agonist, which is a sustained-release prodrug of resiquimod, show potent and sustained anti-tumor benefits (page 5 left column, page 6 left column).
Given Zhu et al, BenchChem Technical Support Team, Lai et al’s teaching about the difference in TLR7/8 function/expression between species, Mullins et al, Zuniga et al’s teaching about the unpredictability of the function between different TLR7/8 agonist, the cited references demonstrate that the function of a TLR7/8 agonist is not predictable.
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples:
The instant specification is only enabling for one example of treating mouse 4T1-luc2 cancer by administering a composition comprising R848 to the target site. The specification is not enabling to use any types of TLR7/8 agonist to treat all types of cancers.
Given the evidence above, the heterogeneity of cancers, unpredictable responsiveness to TLR7/8 agonists, and the various TLR7/8 agonists, one of skill in the art could not reasonably extrapolate the findings for one specific method in a single specific type of cancer in mouse, to unlimited options of administering any TLR7/8 agonist in all of the hundreds of diverse cancers.
In conclusion, the claimed invention does not provide enablement for the treatment of all cancers with any TLR7/8 agonist. Therefore, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
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.
Claims 1, 2, 4, 6, 7, 11, 18, 19, 22, 27, 30, 32, 33, 38, 40 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Tjan-Heijnen et al (J Clin Oncol 27, CRA506, 2009, Volume 27, Number 18 suppl) in view of Goldberg (US 10,413,612, previously published as US 2019/0083626 A1 on March 21 2019, cited as A25 in IDS filed on 02/05/2024).
Claim 1 is drawn to a method of treating cancer, comprising a step of administering to a target site in a cancer subject, a composition comprising an effective amount of an immunomodulatory composition, wherein the target site is or comprises a lymph node dissection site.
Claim 2 is drawn to the method of claim 1, wherein the immunomodulatory composition is characterized by its ability to:(i) induce an innate immune response; and/or (ii) inhibit an immunosuppressive inflammation response.
Claim 4 is drawn to the method of claim 1, wherein the immunomodulatory composition is or comprises: (ii) a biomaterial preparation and at least one immunomodulatory payload.
Claim 6 is drawn to the method of claim 4, wherein the biomaterial preparation comprises at least one polymer.
Claim 7 is drawn to the method of 4, wherein the immunomodulatory payload is or comprises: (i) a modulator of innate immunity.
Claim 11 is drawn to the method of claim 4, wherein the immunomodulatory payload is or comprises:(i) a TLR7/8 agonist. Claim 11 is rejected because it is unclear the agonists included in the claim. For examination purpose, the claim is interpreted to include an agonist of TLR7, or TLR8, or both TLR7 and 8.
Claim 18 is drawn to the method of claim 1, wherein the cancer subject is a tumor resection subject.
Claim 19 is drawn to the method of claim 1, comprising, prior to the step of administering, removing at least one lymph node that is proximal to a tumor in the cancer subject, optionally wherein the removal of at least one lymph node is performed:(i) intraoperatively during a tumor resection surgery, or (ii) in a different operation from a tumor resection surgery.
Claim 22 is drawn to the method of claim 19, further comprising intraoperative administration of a second immunomodulatory composition at the tumor resection site, optionally wherein the second immunomodulatory composition administered at the tumor resection site is the same or is different from the immunomodulatory composition administered at the lymph node dissection site.
Claim 27 is drawn to the method of claim 1, wherein the lymph node is or comprises: a sentinel lymph node, a draining lymph node, an axillary lymph node, an inguinal lymph node, a femoral lymph node, a facial lymph node, a neck lymph node, a cervical lymph node, a supraclavicular lymph node, a subclavian lymph node, a pectoral lymph node, a mediastinal lymph node, a pelvic lymph node, a mesenteric lymph node, and/or a retroperitoneal lymph node.
Claim 30 is drawn to the method of claim 1, comprising intraoperative administration of the composition to the target site in a cancer subject undergoing a lymph node dissection surgery.
Claim 32 is drawn to the method of claim 1, wherein the cancer being treated is at least one of: a carcinoma, a sarcoma, a germ cell tumor, a blastoma, a lymphoma, a skin cancer, a melanoma, a pharyngeal head and neck cancer, a thyroid cancer, a brain cancer, a bladder cancer, a gastrointestinal tract cancer (e.g., a stomach cancer), a thoracic cancer, a lung cancer, a breast cancer, a colorectal cancer, a genitourinary cancer, a kidney cancer, a prostate cancer, a gynecologic cancer, a testicular cancer, an ovarian cancer, and or an uterine cancer.
Claim 33 is drawn to the method of claim 4, wherein the biomaterial preparation comprises:(i) a thermo-responsive polymer, optionally wherein the thermo-responsive polymer is or comprises a poloxamer; and/or (ii) a carbohydrate polymer, optionally wherein the carbohydrate polymer comprises hyaluronic acid and/or chitosan or a modified chitosan.
Claim 38 is drawn to the method of claim 1, wherein the method reduces the likelihood of: (i) developing one or more symptoms associated with lymphedema and/or lymphocele as compared to a lymph node dissection without administration of an immunomodulatory composition; and/or (ii) developing one or more metastatic lesions as compared to a lymph node dissection without administration of an immunomodulatory composition.
Claim 40 is drawn to the method of claim 1, wherein the administration at the lymph node dissection site is performed by implantation or injection.
Claim 42 is drawn in a method of treating cancer by intraoperative administration of a combination of a biomaterial preparation and an immunomodulatory payload to a subject suffering from cancer, the improvement that comprises: administering the combination at a lymph node dissection site rather than or in addition to at a tumor resection site.
Tjan-Heijinen et al teaches in breast cancer patients that have micrometastases (pN1mi) in the sentinel lymph node (SN), omission of completion axillary lymph node dissection (cALND) or omission of axillary radiotherapy (ax RT) leads to higher 5-year axillary recurrence (AR) rate, and therefore suggests these patients should undergo cALND or ax RT to prevent AR (whole document).
Tjan-Heijinen et al fails to teach the method of treating cancer comprising administering a composition comprising an effective amount of a TLR7/8 agonist to a target site that is or comprises a lymph node dissection site.
However, Goldberg teaches a method of treating cancer comprising intraoperative administration at a tumor resection site of a subject suffering from cancer an effective amount of a combination of a biomaterial and a toll-like receptor 7 and 8 (TLR7/8) agonist, wherein the biomaterial is or comprises hyaluronic acid (see Goldberg claim 1). R848 (also known as Resiquimod), a TLR 7/8 agonist, is an agonist of innate immunity (column 95 line 22). Hyaluronic acid is a polymer and a biomaterial preparation. The drug composition can be placed within a tumor resection site or in a sentinel lymph node (column 11 line 47-51). In addition, the local tumor recurrence is prevented most effectively when an agonist of innage immunity (R848 or STING-RR) is administered via the hydrogel (Column 95 line 20-23). This is relevant to claims 1, 2, 4, 6, 7, 11, 18, 22, 27, 30, 33, 40 and 42.
Goldberg also teaches the cancer is a sarcoma, carcinoma, lymphoma, germ cell tumor, or blastoma (column 3 line 35-37). This is relevant to claim 32.
Goldberg further teaches the method is useful preventing tumor recurrence and/or metastasis (reduces the likelihood of developing one or more metastatic lesions) (column 3 line 39-46, column 27 line 27-31). This is relevant to claim 38.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Tjan-Heijinen et al and Goldberg, to administer a TLR7/8 agonist at the lymph node dissection site that has micrometastases, to treat cancer and prevent cancer recurrence, because doing so would reduce the rate of cancer recurrence. One would be motivated to do so because treating cancer positive lymph nodes is common practice in the art and it can provide survival benefits for the patients (Tjan-Heijinen et al) and the method of administering a composition comprising R848 placed at tumor resection site has been shown to be able promote animal survival and most effectively preventing tumor recurrence (Goldberg). One would have a reasonable expectation of success in making the combination because a composition comprising R848 is shown to promote animal survival and prevent cancer recurrence when administered at a tumor resection site, the same would apply to cancer positive lymph nodes dissection or resection site.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claims 25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Tjan-Heijnen et al in view of Goldberg as applied to claims 1, 2, 4, 6, 7, 11, 18, 19, 22, 27, 30, 32, 33, 38, 40 and 42 above, and further in view of Rodriguez-Bigas et al (Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003).
Claim 25 is drawn to the method of claim 18, wherein tumor resection surgery comprises removal of at least a portion of an organ comprising a tumor.
Claim 26 is drawn to the method of claim 25, wherein the tumor resection surgery further comprises anastomosis after the removal of at least a portion of the organ comprising the tumor.
Claims 25 and 26 are rejected because it is unclear the precise size of the portion of an organ to be removed. For examination purpose, the term “at least a portion of an organ” is interpreted to include as little as one cell of the organ and as big as the whole organ can be removed.
The teachings of Goldberg and Tjan-Heijnen et al have been discussed previously.
Goldberg and Tjan-Heijnen et al fail to teach the limitation wherein tumor resection surgery comprises removal of at least a portion of an organ comprising a tumor as cited in claim 25, and wherein the tumor resection surgery comprises anastomosis as cited in claim 26.
However, removal of at least a portion of an organ comprising a tumor to obtain a tumor-free margin, and anastomosis to restore normal flow after removing tumors, are both common practices in cancer treatment. For instance, Rodriguez-Bigas teaches in colon cancer management, surgical principles include en bloc resection of any organs or structures attached to the tumor, and a margin of normal bowel be obtained on either size of the tumor (section Resection Margins). In addition, all the procedures can be performed with a hand-sewn or stapled anastomosis.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Goldberg and Tjan-Heijinen et al and Rodriguez-Bigaz et al, to remove at least a portion of an organ comprising a tumor and perform anastomosis after removal of at least a portion of the organ comprising the tumor, because doing so would increase the chance of obtaining tumor-free environment and restore the normal function of the organ. One would be motivated to do so is that the surgical procedures would increase the chance of obtaining tumor-free environment and would restore the normal function of the organ. One would have a reasonable expectation of success in making the combination because tumor resection surgery comprises removal of at least a portion of an organ comprising a tumor, and anastomosis after the surgery removal is common practice in the art.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Tjan-Heijnen et al in view of Goldberg as applied to claims 1, 2, 4, 6, 7, 11, 18, 19, 22, 27, 30, 32, 33, 38, 40 and 42 above, and further in view of Scaglioni et al (Transl Cancer Res. 2020 May; 9(5): 3167-3171).
Claim 31 is drawn to the method of claim 30, wherein the lymph node dissection surgery further comprises anastomosis.
The teachings of Goldberg and Tjan-Heijnen et al have been discussed previously.
Goldberg and Tjan-Heijnen et al fail to teach the lymph node dissection surgery further comprises anastomosis.
However, Scaglioni et al teaches lymphedema is very common after cancer-related surgeries and adjuvant therapies and breast cancer-related lymphedema is a rather common complication in particular when axillary lymph node dissection and radiotherapy are required (page 3167 left column). Lymphedema can deeply affect the quality of life of the patients and may lead to severe complications (page 3167 left column). Scaglioni et al reviews the a few different options to restore a functional pathway for lymph drainage and suggests lymphovenous anastomosis (LVA) can become the gold standard for the treatment lymphedema after lymph node dissection surgery in cancer patients (whole document).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Goldberg and Tjan-Heijinen et al and Scaglioni et al, to perform anastomosis after lymph node dissection because doing so would have benefits to the patients, such as reduced likelihood of lymphedema and complications. One would be motivated to do so because lymph node anastomosis can restore the function of lymph drainage and reduce the likelihood of lymphedema. One would have a reasonable expectation of success in making the combination because lymph node anastomosis, such as lymphovenous anastomosis (LVA) has been successfully in the art.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Tjan-Heijnen et al in view of Goldberg as applied to claims 1, 2, 4, 6, 7, 11, 18, 19, 22, 27, 30, 32, 33, 38, 40 and 42 above, and further in view of Jung et al (Carbohydrate Polymers Volume 156, 2017, pages 403-408).
Claim 37 is drawn to the method of claim 4, wherein the biomaterial preparation comprises a poloxamer at 7-12.5% (w/w), and one or both of a hyaluronic acid at 0.5-7% (w/w) and chitosan or a modified chitosan at 0.5-7% (w/w).
The teachings of Goldberg and Tjan-Heijnen et al have been discussed previously.
Goldberg and Tjan-Heijnen et al fail to teach the biomaterial preparation as cited in claim 37.
However, a thermosensitive hydrogel comprising hyaluronic acid (HA) and poloxamer are well established to deliver therapeutic drugs to patients. For example, Jung et al teaches an injectable thermos-sensitive hydrogel comprising HA and Pluronic F-127 (poloxamer) that has enhanced mechanical strength of hydrogel and elicits a sustained release of the drug (see abstract). Jung et al tests the solid-gel transition curves of the hydrogel comprising 1% HA and 0-30% F-127 and teaches that the incorporation of HA could lower the Pluronic concentration for gelation (page 4).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Goldberg and Tjan-Heijinen et al and Jung et al, to use a hydrogel comprising HA and Pluronic and also optimize the concentration of HA and Pluronic, to effectively deliver a TLR7/8 to the target site, because one of skill in the art would have been motivated to optimize the concentration of the components in a composition to achieve desired property. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine the optimum concentration of a known agent to improve the property of a composition. The determination of the concentration for a known compound is a matter of routine experimentation using well-established methods in the field, and can be reasonably expected to produce predictable results. Regarding the overlapping dose ranges of the instant claims and Jung et al’s teaching, according to MPEP 2144.05, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Relevant Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Park et al (Sci. Transl. Med. 10, eaar1916, 2018, cited as C108 in IDS filed 02/05/2024) teaches a biodegradable hydrogel comprising R848, which is an agonist of Toll-like receptor 7/8 and an agonist of innate immunity, is placed in the tumor resection site and is used to treat metastasis cancer. The hydrogel is hyaluronic acid based.
Conclusion
No claims are allowed.
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/TIAN YANG/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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