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 .
The Applicants’ Amendment to the Claims filed on April 10, 2026 is entered.
Priority
This is the First Office Action on the Merits of US 18/039,871 filed on 06/01/2023 which is a 371 of PCT/EP2021/084265 filed on 12/03/2021 which claims foreign priority benefit of EP 20211880.8 filed on 12/04/2020. The Filing Receipt filed on 07/08/2025 is controlling. Please note that instant claim 10 does not receive priority to the foreign priority document EP 20211880.8 because this document does not disclose the elements of SGN-40, and ABBV-927. Effective filing date for claim 10 is 12/03/2021.
Claim 15 is canceled.
Claims 1-14 and 16-20 are pending.
Claims 6 and 11 are withdrawn to non-elected species.
Claims 1-5, 7-10, 12-14 and 16-20 are under examination.
Election/Restrictions
Applicant’s election without traverse of:
-the Species of (A) being CDX-1140 as the type of CD40 agonist; and
-the Species of (B) being the administration of IL-15 subcutaneously and the administration of CD40 agonist intravenously,
in the reply filed on April 10, 2026 is acknowledged.
Claims 6 and 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species of type of CD40 agonist and type of administration, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on April 10, 2026.
Information Disclosure Statement
The IDS filed on 09/15/2023 has been considered by the examiner.
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.
Claim 3 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation "the dose of said IL-15 and CD40 agonist required to obtain a therapeutic effect in said subject, when administered alone" in lines 2-4. There is insufficient antecedent basis for this limitation in the claim because there is no prior reference in the claims to a dose of said IL-15 and CD40 agonist required to obtain a therapeutic effect in said subject, when administered alone.
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.
Claims 1-5, 7-9, 12-14 and 16-20 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.
Claims are drawn to a method of treating melanoma in a subject in need thereof, the method comprising administering to the subject a combination comprising IL-15 and a CD40 agonist. Thus, claims require the critically essential element of a genus of CD40 agonists which are functional to treat melanoma in subject when in combination with IL-15. The genus of CD40 agonists is described in the instant specification as encompassing a molecule which specifically binds to the subject’s CD40 molecule and increases/enhances/induces one or more CD40 activities (pg. 6, ln. 14-16). Thus, the claimed genus of CD40 antagonist is defined by function but without correlating to structure. For example, the genus of CD40 agonists includes a vast number of potential molecules of unrelated structure, including: nucleic acids, small molecules and generic antibodies.
For example, regarding the subgenus of an agonistic antibody that binds CD40, this subgenus is defined by binding function. See MPEP §2163(I)(A) which states:
"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. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence."
In this case, antibodies generally share certain characteristics such as Fc regions or hinge regions. However, these structures are not correlated with the binding function of the antibody. The hyper variable regions (HVRs), i.e., complementarity determining regions (CDRs) of an antibody, are well established in the art as the portion of the binding region which imparts the specificity of an antibody. However, there is no way to a priori look at an antigen sequence (CD40) and envisage the combination of six CDRs that will bind that antigen. First, even highly related CDRs may not bind the same target. See for example Kussie (“A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity” 1993 J Immunol Vol 152, No 1:pages 146-152)) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (c.g., abstract).
The specification discloses eight antibodies identified by name: Selicrelumab, APX005M, ChiLob7/4, ADC-1013, SEA-CD40, CDX-1140, SGN-40, and ABBV-927.
However, as discussed above, without any way to determine how broad the genus of such antibodies are, there is no way to determine if these antibodies represent the full breadth of what is claimed. The disclosure of these specific antibodies would not convey to the artisan that Applicant was in possession of the full genus of all antibodies which possess the required functions nor does it allow the skilled artisan to envisage the specific structure of such antibodies. Further note the decision in Amgen V. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to "claim antibodies by describing something that is not the invention, i.e., the antigen". This decision has precipitated guidance to the Office instructing that the portion of MPEP 2163 regarding the "newly characterized antigen test" (indicating a well-characterized antigen is sufficient to satisfy written description for antibodies which bind that antigen) should no longer be used and that contrary materials should not be relied upon as reflecting the current state of the law.
Note that instant claim 10 recites the eight antibodies from the specification and is not included in this rejection. However, the rest of the instant claims encompass a broad genus of agonistic anti-CD40 antibodies including a variant which is construed to include no particular structure so long as the function is retained.
Further, the state of the art does not provide a representative set of CD40 agonists encompassed by the claims so that one of ordinary skill in the art would be able to envision whether a given species of CD40 agonist would possess the required function as a therapeutic for treating melanoma when in combination with IL-15. For example, the state of the art describe a subset of functional CD40 agonist antibodies, including ADC-1013 (see Ellmark et al, below) or CDX-1140 (see Levy et al below). Further, Zhang et al disclose Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer. Specifically Interleukin-15 combined with the specific anti-CD40 antibody FGK4.5 provides enhanced therapeutic efficacy for murine models of colon cancer. (See Zhang et al in “Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer” (PNAS vol 106 No 18, May 5, 2009; pages 7513-7518).
However, the state of the art does not provide a representative set of the myriad types of molecules encompassed by the term CD40 agonist so that one of ordinary skill in the art would be able to envision whether a given species would be included in the claimed genus.
For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. The MPEP states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not a sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as be structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXlS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these.
Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond those compounds specifically disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus. While having written description of the molecules listed in instant claim 10, and compounds identified in the specification tables and/or examples, the specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims. Given this lack of description of representative species encompassed by the genus of the claim, the specification does not sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the entire scope of the claimed invention.
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.
Claims 1-3, 9-10, 12, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ellmark et al (US 2017/0226217, published 08/10/2017).
Regarding claim 1, Ellmark et al discloses a method of treating melanoma by administering to a subject a combination therapy comprising an anti-CD40 antibody and a further immunotherapeutic anti-cancer agent being Interleukin-15. (See Embodiments T, & FF; reference claim 3, para 0089, 0263-0283). For example, Ellmark et al recites in para 0110:
The method of the invention comprises
(a) administering to the subject a therapeutically effective amount of an antibody that specifically binds to CD40 and that is retained at the tumour site following administration, and optionally
(b) systemically administering to the subject a therapeutically effective amount of an additional therapeutic agent. Retention of an antibody at a tumour site is described in more detail below.
Steps (a) and (b) may be carried out simultaneously.
Alternatively steps (a) and (b) may be carried our sequentially provided step (a) precedes step (b). In step (a), the anti-CD40 antibody is preferably administered locally to the tumour.
Ellmark et al disclose using the combination therapy for treating a tumour in a subject where the tumour is a melanoma. (See para 0089.) Ellmark et al disclose the further immunotherapeutic agent with efficacy in the treatment of cancer is Interleukin-15 (see para 0283; Embodiments T and FF).
Regarding claim 2, Ellmark et al discloses that the CD40 agonist (antibody) is administered in a lower dose than needed for a therapeutic effect in the subject which is construed to meet the limitation of a subtherapeutic dose. See para 0111 which states:
The method of the invention has several advantages. First, because the anti-CD40 antibody is retained at the tumour site, it is highly effective as a treatment. Furthermore, there is reduced systemic exposure to anti-CD40 antibodies, allowing a lower dose of antibody to be used and resulting in fewer side-effects. When step (b) is carried out the treatment effect is further improved.
Regarding claim 3, Ellmark et al discloses that this subtherapeutic dose of the CD40 agonist (antibody) is a dose which is lower than the dose of CD40 agonist required to obtain a therapeutic effect in said subject, when administered alone. (See para 0111 just above).
Regarding claim 9, Ellmark et al discloses that the combination is in the form of a pharmaceutical composition. (See Embodiment DD; ref claim 30).
Regarding claim 10, Ellmark et al discloses that said CD40 agonist is ADC-1013. (See Example 3-in vivo murine melanoma model; Example 7- Effect of ADC-1013 on wildtype B16 melanoma in mice.)
Regarding claim 12, Ellmark et al discloses that the additional therapeutic agent and CD40 agonist are administered simultaneously. (See para 0110 above).
Regarding claim 14, Ellmark et al discloses that said melanoma is metastatic melanoma. (See Embodiment E).
Thus, Ellmark et al anticipates claims 1-3, 9-10, 12, and 14.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 7-10, 12-14 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ellmark et al (US 2017/0226217, published 08/10/2017), in view of Liot et al (US 20200283518 published 09/10/2020, filed on 02/28/2020), in view of Conlon et al in “Cytokines in the Treatment of Cancer” (J of Interferon & Cytokine Res; 2019 Vol 39, No 1; entire document), in view of Levy et al (US 20220175920 published 06/09/2022, filed on 03/26/2020.
Regarding claim 1, Ellmark et al discloses a method of treating melanoma by administering to a subject a combination therapy comprising an anti-CD40 antibody and a further immunotherapeutic anti-cancer agent being Interleukin-15. (See Embodiments T, & FF; reference claim 3, para 0089, 0263-0283). For example, Ellmark et al recites in para 0110:
The method of the invention comprises
(a) administering to the subject a therapeutically effective amount of an antibody that specifically binds to CD40 and that is retained at the tumour site following administration, and optionally
(b) systemically administering to the subject a therapeutically effective amount of an additional therapeutic agent. Retention of an antibody at a tumour site is described in more detail below.
Steps (a) and (b) may be carried out simultaneously.
Alternatively steps (a) and (b) may be carried our sequentially provided step (a) precedes step (b). In step (a), the anti-CD40 antibody is preferably administered locally to the tumour.
Ellmark et al disclose using the combination therapy for treating a tumour in a subject where the tumour is a melanoma. (See para 0089.) Ellmark et al disclose the further immunotherapeutic agent with efficacy in the treatment of cancer is Interleukin-15 (see para 0283; Embodiments T and FF).
Regarding claim 2, Ellmark et al discloses that the CD40 agonist (antibody) is administered in a lower dose than needed for a therapeutic effect in the subject which is construed to meet the limitation of a subtherapeutic dose. See para 0111 which states:
The method of the invention has several advantages. First, because the anti-CD40 antibody is retained at the tumour site, it is highly effective as a treatment. Furthermore, there is reduced systemic exposure to anti-CD40 antibodies, allowing a lower dose of antibody to be used and resulting in fewer side-effects. When step (b) is carried out the treatment effect is further improved.
Regarding claim 3, Ellmark et al discloses that this subtherapeutic dose of the CD40 agonist (antibody) is a dose which is lower than the dose of CD40 agonist required to obtain a therapeutic effect in said subject, when administered alone. (See para 0111 just above).
Regarding claim 9, Ellmark et al discloses that the combination is in the form of a pharmaceutical composition. (See Embodiment DD; ref claim 30).
Regarding claim 10, Ellmark et al discloses that the CD40 agonist is ADC-1013. (See Example 3-in vivo murine melanoma model; Example 7- Effect of ADC-1013 on wildtype B16 melanoma in mice.) In addition, see Levy et al (below) for the limitation of the CD40 agonist being CDX-1140.
Regarding claim 12, Ellmark et al discloses that the additional therapeutic agent and CD40 agonist are administered simultaneously. (See para 0110 above).
Regarding claim 14, Ellmark et al discloses that said melanoma is metastatic melanoma. (See Embodiment E). Further, Ellmark et al discloses that types of melanoma include Lentigo maligna, Lentigo maligna melanoma, Superficial spreading melanoma, Acral lentiginous melanoma, Mucosal melanoma, Nodular melanoma, Polypoid melanoma, Desmoplastic melanoma, Amelanotic melanoma, Soft-tissue melanoma, Melanoma with small nevus-like cells, Melanoma with features of a Spitz nevus and Uveal melanoma, and metastatic. (See para 0089-0090).
Regarding claim 13, Ellmark et al discloses that the CD40 agonist may be administered intravenously, intradermally or subcutaneously. (See Example 3-in vivo murine melanoma model; Example 7- Effect of ADC-1013 on wildtype B16 melanoma in mice; Example 11.) However, Ellmark et al does not show an embodiment that explicitly shows IL-15 administered intravenously, intradermally or subcutaneously. Conlon et al (see Conlon discussion below) discloses a daily bolus infusion of IL-15 in a phase I clinical trial for adults with refractory metastatic malignant melanoma as well as 22 patients receiving IL-15 SC (subcutaneously) and one cohort receiving rhIL-15 by continuous IV infusion for two days at 2.0 mcg/kg/day. (see Conlon et al page 13, right col.).
In addition, regarding the claims directed to dose amounts, Ellmark et al disclose dose amounts for the CD40 that meet the limitations of claims 4, 8, and 16-17 for CD40 agonist as follows.
Regarding claim 4, Ellmark et al discloses that said CD40 agonist is administered at a dose of about 20 ug per kg body weight which meets the limitation of from about 20 µg to about 800 µg per kg body weight. See Example 4, para 0322 showing low dose intratumoral, administration of 1 ug per dose into mouse model subjects. Since the average weight of a mouse is about 0.02-0.05 kg body weight, the doses of Ellmark et al meet the limitation of about 20 ug per kg body weight. Also, Example 8 shows peritumorally administration of CD40 agonist at 30 ug per dose which meets the limitation of about 600 ug per body weight.
Regarding claim 8, Ellmark et al discloses that said CD40 agonist is administered at a dose of less than 300 µg per kg body weight.
Regarding claim 16, Ellmark et al discloses within claim 4 that: said CD40 agonist is administered at a dose of from about 30 to about 600 µg per kg body weight.
Regarding claim 17, Ellmark et al discloses within claim 16 that: said CD40 agonist is administered at a dose of from about 40 to about 300 µg per kg body weight.
However, while Ellmark et al show a combination therapy of a CD40 agonist and IL-15 in a single embodiment, they do not show the dose amounts of the present claims for CD40 agonist combined with dose amounts for IL-15 in a single embodiment.
Conlon et al discloses dose amounts for IL-15 and suggest combination therapy with a CD40 agonist. (See page 14, Section headed: “IL-15 plus agonistic anti-CD40 antibody”.) Conlon et al disclose that “[i]n muring models, the combination of an agonistic anti-CD40 monoclonal antibody and IL-15 augmented tumor-specific CD8 T cells and antitumor efficacy-an approach that is being translated into clinical trials.” (See page 16, right col, last two sentences.) Conlon et al disclose that IL-15 was administered to patients for treating adults with refractory metastatic malignant melanoma but was generally toxic at therapeutic dose amounts. (See page 13, right col. for dose amounts provided to melanoma patients in a phase I trial.). Conlon et al disclose that a combination therapy using IL-15 was more effective than IL-15 alone. (See page 13, right col.) Conlon et al explicitly suggest combining IL-15 therapy with agonistic anti-CD40 antibody. Conlon et al showed that the combination of IL-15 with anti-CD40 “produced markedly additive effects that were curative in the majority of mice when compared to either agent alone”. (See page 14, right col.)
Regarding claim 5, Conlon et al discloses that said IL-15 is administered to adult patients with melanoma at a dose of 0.3 mcg/kg/day without dose-limiting toxicities. In contrast, administration of doses of 3 mcg/kg/day showed toxicity. The dose of 0.3 mcg/kg/day of Conlon et al meets the claim 5 limitation of about 0.1 to about 50 µg per kg body weight. (See page 13, right col., para 2.)
Regarding claim 7, Conlon et al discloses that the IL-15 is administered by IV bolus, continuous IV, or subcutaneously. Also, Conlon et al discloses that the IL-15 may be administered at a dose of 0.3 mcg/kg/day which meets the claim 7 limitation of less than 2 µg per kg body weight.
Regarding claim 18, Conlon et al discloses that said IL-15 is administered to adult patients with melanoma at a dose of 0.3 mcg/kg/day without dose-limiting toxicities. In contrast, administration of doses of 3 mcg/kg/day showed toxicity. The dose of 0.3 mcg/kg/day of Conlon et al meets the claim limitation of about 0.1 to about 20 µg per kg body weight. (See page 13, right col., para 2.)
Regarding claim 19, Conlon et al discloses that the IL-15 is administered to adult patients with melanoma at a dose of 0.3 mcg/kg/day which meets the limitation of a dose of from about 0.1 to 2 µg per kg body weight. (See page 13, right col., para 2.)
Regarding claim 20, Conlon et al discloses that said IL-15 is administered to adult patients with melanoma at a dose of 0.3 mcg/kg/day without dose-limiting toxicities. In contrast, administration of doses of 3 mcg/kg/day showed toxicity. The dose of 0.3 mcg/kg/day of Conlon et al meets the claim 20 limitation of less than 2 µg per kg body weight.
Regarding claim 1, Levy et al disclose a method of treating cancer in a subject by administering to the subject a combination therapy comprising a CD40 agonist. See reference claim 20. Levy et al disclose that IL-15 is induced by the administration of the CD40 agonist. (See para 0282; Levy et al disclose the CD40 agonist administration induces the secretion of IL-15 (See para 0008; para 0302; FIG 3; ref claim 16).
Regarding claim 9, Levy et al disclose the CD40 agonist can be administered in a pharmaceutical composition in combination therapy. (See para 0256; ref claim 14-15; para 0319 FIG 17 showing effects of administering CD40 agonists to mice models.
Regarding claim 10, Levy et al discloses that said CD40 agonist is a CD40 antibody or antigen binding fragment may be CDX-1140 (para 0228; 0400) and SGN-40 (para 0226).
Regarding claim 9, Levy et al discloses that the combination is in the form of a pharmaceutical composition. (See para 0257).
Regarding claim 1, Liot et al disclose a method of treating cancer in a subject by administering to the subject a combination of anti-cancer agents including a CD40 agonist and an IL-15. (See para 0044, 0114). In paragraph 0044, Liot et al recites: “In some embodiments, the disclosed methods include administering a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor and a therapeutically effective amount of a PD-1 inhibitor in combination with an additional therapeutic agent or therapy”, stating that the “additional therapeutic agent or therapy may be administered for increasing anti-tumor efficacy, for reducing toxic effects of one or more therapies and/or for reducing the dosage of one or more therapies”. The additional therapeutic agent may be a CD40 agonist and IL-15.
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art would have been motivated to combine the elements of the Ellmark et al reference for treating melanoma with the combination of cited references for the rationale of providing a successful treatment for melanoma to a subject. The rationale for combining the IL-15 and CD-40 agonist agents would be to be able to enhance immunotherapy effects while lowering the individual toxicity from the chemotherapy by using subtherapeutic doses as expressly suggested by the references of Ellmark et al, Liot et al and Conlon et al.
It would have been obvious to one of ordinary skill in the art to combine the elements of the cited references because each of the references suggest a therapeutic combination of a CD-40 agonist in combination with a IL-15 for treating cancer. Specifically, Ellmark et al, Liot et al and Conlon et al explicitly suggest that combination therapy allows for subtherapeutic doses of the agents alone to reduce toxicity. Further, the combination of references disclose many type of available CD40 agonists which are successful for specifically treating melanoma. Further, the cited combination of references disclose the claimed doses for the IL-15 and CD40 agonist. Regarding the doses for administering and the type of administering being a bolus IV, continuous IV, intratumoral, or subcutaneous, it is noted that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP § 2144.05. The combination of cited references disclose the claimed dose ranges and the claimed routes of administration. Therefore, the claimed limitations of routes of administration is considered optimization through routine experimentation, and would be obvious to one of ordinary skill in the art. Furthermore, a prima facie case of obviousness based on optimization may only be rebutted by evidence showing that the claimed element is critical, generally by proof that the claimed range achieves unexpected results relative to the prior art. See MPEP § 2144.05.
In view of the high skill level in the art it is considered that one of ordinary skill in the art would have had a reasonable expectation of success to combine the elements of the cited references to arrive at the presently claimed invention.
Conclusion
No claim is allowed.
Related art which may be applied in a future office action if appropriate.
Wong et al “IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer” PNAS Vol 120, No 35, August 1, 2023. Wong et al is post-filing art showing humanized immunocompetent orthotopic bladder tumor models, therapeutic augmentation of this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer.
Bilic et al (WO 2017106656 A1 published 06/22/2017, filed on 02/28/2020). Bilic et al disclose a method of treating cancer using a combination of therapeutic agents including IL-15 and a CD40 agonist (see page 12, lines 20-23). Bilic et al disclose the cancer is melanoma (e.g., page 7, line 20; page 9, lines 14-40).
Silva et al “De novo design of potent and selective mimics of IL-2 and IL-15” (Nature January 2019 565 (7738): pages 186-191). Tested therapeutic efficacy of Neo-2/15 in B16F10 mouse model for melanoma and CT26 mouse model for colon cancer. (See page 6, para 2; pages 13-16; FIG E1 (colon) FIG E2 (melanoma); entire document).
Flores et al in “Anticancer Cytokines: Biology and Clinical Effects of IFN-alpha2, IL-2, IL-15, IL-21, and IL-12” (Semin Oncol 2015 August Vol 42, No 4: pages 539-548).
Smith et al “Future directions in bladder cancer immunotherapy: towards adaptive immunity” Immunotherapy, Future Medicine LTD, UK, Vol 8, No 3, February 10, 2016, pages 351-365. Smith et al disclose relevant immunotherapies, including IL-12, IL-15 and anti-CD40 that are deserving of clinical consideration for treating bladder cancer.
Van Audenaerde et al “Novel combination immunotherapy for pancreatic cancer: potent anti-tumor effects with CD40 agonist and interleukin-15 treatment” (Clinical & Translational Immunology, Vol 9, e1165; pages 1-15, August 15, 2020; IDS ref). Van Audenaerde et al disclose combination therapy comprising IL-15 and a CD40 agonist for use in the treatment of pancreatic cancer. CD40 agonists include a CD40 antibody or antigen binding fragment thereof such as selected from: Selicrelumab, APX005M, ChiLob7/4, ADC-1013, SEA- CD40, CDX-1140, SGN-40, ABBV-927.
Van Audenaerde et al (Poster Presentation Abstract # PO-417 Anti-tumoural effects of IL-15 an CD40 stimulation as a novel combination immunotherapy for pancreatic cancer”. June 29, 2018, pages A393.2.A394). Van Audenaerde et al disclose anti-tumoural effects of IL-15 an CD40 stimulation as a novel combination immunotherapy for pancreatic cancer. Van Audenaerde et al disclose a “combination of IL-15 and anti-CD40 exhibits a profound anti-tumour response in two mouse models of PC resulting in prolonged survival and even total eradication of >60% of PCs”, stating that “these data provide a solid proof of principle to advance with this combination strategy”.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
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