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 .
Claim Status
Claims 1, 5-8, 12, 19, 21-25 and new claims 31-35 are under consideration in this office action.
Withdrawn Objections/Rejections
Any objection or rejection of record pertaining to cancelled claim 9 is rendered moot by applicant' s cancellation of said claim.
The objections of claims 19 and 22-23 are withdrawn in view of applicant’s amendment.
The objection to the specification is withdrawn; a substitute specification was filed on December 19, 2025.
The rejection of claims 1, 5-8, 12, and 25 under 35 U.S.C. 112(b) is withdrawn in view of applicant’s amendment to remove the term “optionally”.
The rejection of claims 19, 22, and 25 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 2016/059602 is withdrawn in view of applicant’s amendment to limit the anti-HER3 antibody to CDX-3379.
New Objections/Rejections Necessitated by Amendment
Claim Objections
Claim 19 is objected to because of the following informalities: Claim 19, last line, change “do not administer the treatment” to “not administering to the subject the CDX-3379 and the PD-1 inhibitor” in order to be consistent with the prior language of the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 5-8, 12, 19, 21-25 and new claims 31-35 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.
Claims 1 and 19 are rejected as vague and indefinite for reciting the term “CDX-3379” as the sole means of identifying the antibody. The use of laboratory designations only to identify a particular antibody renders the claims indefinite because different laboratories may use the same laboratory designations to define completely distinct molecules. It is also well known in the art that molecule names can be altered, deleted, amended, or revised over time by inventors and authors. Hence, one of ordinary skill in the art and or competitors would be unable to discern the bounds of the claimed invention. The rejection can be obviated, for example, by amending the claims to identify the antibody target and to specifically and uniquely identify the antibody by heavy and light chain variable region amino acid sequences.
Claim 1 is limited to a cancer cell expressing a PIK3CA gene modification. The term “modification” is indefinite, because it is unclear whether the modification increases, decreases, or has no effect on PIK3CA gene/protein function, which is relevant when treating a specific type of cancer. Without this guidance, the claim reads on any nucleic acid substitution or deletion that induces an amino acid substitution. The specification includes a list of relevant modifications in the amino acid sequence (spec, pg 8). The rejection can be obviated by including these embodiments in the claim.
Claims 7-8, which is dependent on claim 1, recite the limitation “the anti-HER3 antibody”. There is insufficient antecedent basis for this limitation in the claim.
Independent claim 19 recites “the PD-1 inhibitor” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
The term “sufficient” in claim 19 is a relative term which renders the claim indefinite. The term “sufficient” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. “Sufficient to activate” is indefinite because the specification does not provide some standard for measuring the meaning of the degree.
Claim 23, which is dependent on claim 19, recites the limitation “the PI3K/AKT/mTOR pathway”. There is insufficient antecedent basis for this limitation in the claim.
New claims 32 and 34 lack transitional phrase after “the PD-1 inhibitor”. The claims should read “the PD-1 inhibitor is selected from the group consisting of cemiplimab, nivolumab, pembrolizumab, avelumab, durvalumab, and atezolizumab.” Without the “consisting of” phrase, it is unclear whether the inhibitor is limited to only those agents listed.
New claims 33-34 lack a transitional phrase after “a mutation”; it should read “a mutation selected from the group consisting of R115, Y343, G363, E542, E545, C971, R975, and H1047”. Without the “consisting of” phrase, it is unclear whether the mutations are limited to only those sites listed.
New claim 35, which is dependent on claim 25, recites the limitation “the sample”. Claim 25 is directed to a “a biological sample, “a tumor biopsy sample”, “a cell-free DNA sample, and “a liquid sample”. As such, it is unclear which sample of claim 25 claim 35 is to be limited.
Claims 1, 5-6, 12, 21-22, 24-25 and new claim 31 are included in this rejection for being dependent on a rejected base claim and for failing to cure the indefiniteness.
Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112(a)
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, 5-8, 12, 19, 21-25 and new claims 31, 33, and 35 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 claims contain 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
Claims 1, 5-8, 12, 19, 21-25 and new claims 31, 33, and 35 are directed to method of treating head and neck cancer comprising administration of CDX-3379 and a PD-1 inhibitor. Regarding the PD-1 inhibitor, the claims are directed to vast genus of inhibitors that are defined entirely by function.
As detailed below, applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such, applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
Claims 1, 5-8, 12, 19, 21-25 and new claims 31, 33, and 35 are directed to a method of administering a PD-1 inhibitor to a subject. The genus of PD-1 inhibitor encompasses a broad genus of agent that are defined entirely by function, i.e. the inhibition of PD-1. The specification does not provide a consistent structure for all possible substances or fails to provide a representative number of species for the claimed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of PD-1 inhibitor that are antibodies.
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. It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three complementarity determining regions (CDRs) that provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (see Almagro et al, Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1; PTO-892 from 9/22/25).
There is no way to a priori look at an antigen sequence (e.g., PD-1) 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 (PTO-892 from 9/22/25), who demonstrates that a single amino acid change in the heavy chain of an antibody that binds p-azophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (see abstract). Second, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (pg 7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity (see table on pg 11).
While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains.
According to the specification, the applicant has disclosed 6 specific species of anti-PD-1 antibody, which are known in the art and is comprised of specific combinations of heavy chain CDRs and light chain CDRs. However, the specification does not provide adequate written description for the entire claimed genus of anti-PD-1 antibodies, because one skilled in the art would be unable to immediately envision, recognize, or distinguish most of the members comprised within the genus claimed, specifically which heavy chain and light chain amino acid sequences should be combined to yield an antigen-binding region that is capable of binding and inhibiting PD-1.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
In the instant case, the specification provides insufficient direction or guidance concerning the relationship between the structure of the possible antibody to demonstrate possession of the breadth of the genus of anti-PD-1 antibodies encompassed by the instant claim, especially in view of the unpredictability of such an endeavor. The prior art, as evidenced by Edwards et al., 2003 (PTO-892 from 9/22/25), teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
To provide adequate written description and evidence of possession of the claimed genera, 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 the instant case, the only factors present in the claims are a recitation of two generic, broad genera that encompassed a diverse and huge number of possible antibodies and other agents that modulate immune checkpoint proteins. The specification does not provide a consistent structure for all of the possible antibodies/agents and fails to provide a representative number of species for the claimed genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genera.
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only 20 species within the genus.
For claims drawn to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011). An antibody described only by functional characteristic, such as antibody that binds PD-1, without any known or disclosed correlation between that function and the structure of the sequence, is not a sufficient identifying characteristic for written description purposes.
With the exception of specifically disclosed antibodies with specific CDRs, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Therefore, claims 1, 5-8, 12, 19, 21-25 and new claims 31, 33, and 35 do not meet the written description requirement.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 19, 21-25 and new claim 35 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/059602, published April 21, 2016 (“Clarke”) in view of US 2019/0270727, published September 5, 2019 (“Aktoudianakis”; see IDS from 5/24/2022).
Claim 19 is directed to a method of treating a subject with head and neck cancer with the anti-HER3 antibody CDX-3379 and a PD-1 inhibitor, the method comprising a step of determining if the subject will benefit from the CDX-3379 and PD-1 inhibitor therapy.
Clarke teaches a method of treating head and neck cancer (pg 34) comprising administering an anti-HER3 antibody and a PD-1 inhibitor (pg 152), as in claim 19. The combination of anti-HER3 antibody with an anti-PD-1 antibody resulted in greater tumor regression in a mouse model of metastatic renal cell carcinoma and greater anti-tumor efficacy (pg 152), as in the patient that can benefit from the treatment of claim 19.
Clarke teaches that activation of HER3 increases PI3K/AKT pathway and that anti-HER3 antibodies inhibit agonist induced HER3 phosphorylation (pg 125). Clarke teaches validation of an anti-HER3 antibody for its use as a diagnostic for determining HER3 expression; the level of HER3 expression can be used to identify patients that may clinically benefit from anti-HER3 antibody therapy (pg 143), as in the limitations of claim 19 directed to the performance of a diagnostic assay on a biological sample to determine if a subject may benefit from anti-HER3 treatment. Clark teaches that the biological sample may have been removed from a human (e.g., a biopsy) (pg 83), and HER3 was detectable in a kidney tumor sample (pg 148), as in the biological sample of instant claim 19 and the tumor biopsy of instant claim 25. Clarke also teaches that the biological sample for diagnostic purposes is serum (pg 83), which is a component of blood, as in new claim 35.
The Clarke reference does not teach that the level of PD-1 expression on activated T cells is elevated nor does it teach the anti-HER3 antibody CDX-3379.
Aktoudianakis teaches methods for treating cancer comprised of administering PD-1 inhibitors in combination with the anti-HER3 antibody CDX-3379 [0601], as in instant claim 19. Aktoudianakis teaches that PD-1 is highly expressed on activated T cells, and PD-L1/PD-1 signaling is a primary mechanism of cancer immune evasion [0952]. Inhibition of this pathway can reduce tumor size ([0860], [0868]).
Although Clarke does not specifically disclose wherein the subject can benefit from the treatment if the subject expresses a level of PD-1 on a plurality of activated T cells that when blocked is sufficient to activate tumor-killing activity of the T cells, it would have been obvious to one of ordinary skill in the art that a PD-1 inhibitor in combination with CDX-3379 that is efficacious in decreasing tumor volume, as taught by Clarke and Aktoudianakis, would also be effective to activate tumor-killing activity. The ordinary artisan would include the T cell expression methods of Aktoudianakis in the method of Clarke in order to measure PD-1 expression on T cells and then tailor patient specific treatments using PD-1 inhibitor therapeutics. This is because of the need in cancer cell immunotherapy to develop reliable therapeutics for the treatment of cancer that achieve predictable results.
Claims 1, 5-6, 8, 12, and new claims 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/059602 (“Clarke”) in view of US 2014/0037622, published February 6, 2014 (“Boshoff”; see IDS from 5/24/2022) and US 2019/0270727, published September 5, 2019 (“Aktoudianakis”).
The claims are directed to a method of treating PIK3CA gene modified head and neck cancer by administering an anti-HER3 antibody or fragment thereof and an immune checkpoint modulator.
Clarke teaches a method of treating head and neck cancer (pg 34) comprising administering an anti-HER3 antibody and a PD-1 inhibitor (pg 152), as in instant claim 1. This combination of anti-HER3 antibody with anti-PD-1 antibody resulted in greater tumor regression in a mouse model of metastatic renal cell carcinoma and greater anti-tumor efficacy (pg 152), demonstrating that the subject can benefit from the combination therapy. The PD-1 inhibitor may be pembrolizumab, which reads on the PD-1 blocker and antibody of new claims 31-32.
Regarding the limitations of instant claim 8 directed to inhibition of ribosomal protein S6 phosphorylation, Clarke teaches that activation of HER3 increases PI3K/AKT pathway and that anti-HER3 antibodies inhibit agonist induced HER3 phosphorylation (pg 125). Thus, one of ordinary skill will predict that treatment with anti-HER3 antibodies would inhibit HER2 signaling activity, including PI3K and its downstream target S6.
Clarke teaches that the combination therapy of anti-HER3 antibody and checkpoint inhibitor may be used in combination with other chemotherapeutics and/or radiation (pg 63), as in the limitation of instant claim 12.
Clarke does not teach a method of treating a subject with a cancer that expresses PIK3CA gene modifications, as required by instant claim 1.
Boshoff teaches a method of treating head and neck cancer and that head and neck squamous cell carcinoma have genetic alterations, including modified PIK3CA gene [0043], as in instant claim 1. Boshoff teaches a method of treating head and neck cancer that is HPV positive [0005], as in instant claim 5. Boshoff teaches a method for treating head and neck cancer that is a solid tumor or metastatic lesion, as in instant claim 6.
Given that Clarke teaches a method of treating head and neck cancer by administering a combination therapy comprising an anti-HER3 antibody and an immune checkpoint inhibitor and further given that Boshoff teaches species of head and neck squamous cell carcinoma associated with modification in the PIK3CA gene or head and neck cancer related to HPV infection, it would have been obvious to the ordinary artisan to treat the subjects of Boshoff with the treatment method of Clarke. The motivation to do some comes from Boshoff, who teaches that patients with a head and neck cancer who are HPV-positive exhibit alterations in PI3K activity and that these patients are more likely to benefit from treatment with a PI3K inhibitor [0004]. As the anti-HER3 antibody of Clarke decreases PI3K activity, it would have been obvious to the ordinary artisan that the method of Clarke for treatment of head and neck cancer would be applicable to different types of head and neck cancer that are associated with an aberrant upregulation PI3K; applying a known technique to a known disease ready for improvement will yield predictable results (see MPEP 2143).
Clarke in view of Boshoff does not teach the anti-HER3 antibody CDX-3379, as required by instant claim 9.
Aktoudianakis teaches methods for treating cancer comprised of administering PD-1 inhibitors in combination with the anti-HER3 antibody CDX-3379 [0601], as in instant claim 9.
Given that Clarke in view of Boshoff teaches a method of treating head and neck cancer with a combination therapy of anti-HER3 antibody and an immune checkpoint inhibitor and Aktoudianakis teaches the claimed anti-HER3 antibody, it would have bene obvious to one of ordinary skill in the art to use the antibody of Aktoudianakis in place of the anti-HER3 antibody of Clarke. This is because, as stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious.
Claims 1, 5-8, 12 and new claims 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/059602 (“Clarke”) in view of US 2014/0037622 (“Boshoff”) and US 2019/0270727 (“Aktoudianakis”), as applied to claims 1, 5-6, 8, 12, and 31-32 above, and further in view of Haratani et al, published December 3, 2019 (see PTO-892 from 9/22/25).
The teachings of Clarke in view of Boshoff and Aktoudianakis are discussed above; this combination of references does not teach a method of treating cancer wherein the head and neck cancer is resistant to a PD-1 treatment in the absence of the anti-HER3 antibody, as required by instant claim 7.
Haratani et al teaches that combination therapy with PD-1 inhibitor and anti-HER3 antibody-drug conjugate significantly enhances the anti-tumor immunity of PD-1 blockade in a syngeneic mouse tumor model that is refractory to anti-PD-1 therapy (abstract).
Given that Clarke in view of Boshoff teaches that anti-HER3 antibody and PD-1 inhibitor combination therapy results in greater tumor regression in a mouse model of cancer and greater anti-tumor efficacy in subjects with a cancer expressing a PIK3CA gene modification, and further given Haratani et al teaches improved anti-tumor efficacy of combination therapy in an animal that is refractory to anti-PD-1 therapy, it would have been obvious to one of ordinary skill in the art to apply the treatment method of Clarke in view of Boshoff to a patient who is non-responsive to anti-PD-1 monotherapy. One would do so and have a reasonable expectation of successfully treating this patient, as the combination therapy demonstrates improved anti-tumor efficacy over monotherapy.
Claims 1, 5-6, 8, 12, and new claims 31-34 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/059602 (“Clarke”) in view of US 2014/0037622, published February 6, 2014 (“Boshoff”) and US 2019/0270727, published September 5, 2019 (“Aktoudianakis”), as applied to claims 1, 5-6, 8, 12, and 31-32 above, and further in view of Huang et al, published September 15, 2019 (instant PTO-892).
The teachings of Clarke in view of Boshoff and Aktoudianakis are discussed above; this combination of references does not teach the method wherein the PIK3CA gene comprises the mutation R115.
Huang teaches the mutation R115P in PIK3CA in therapy-resistant breast cancer patients (see abstract). In CCK-8 assay, cells transfected with R115P mutant exhibited enhanced proliferation (pg 6057, column 2). This mutation also promote cell migration and upregulates PI3K pathway (pg 6060, column 1).
Given that Clarke, Boshoff, and Aktoudianakis teach a method of treating head and neck cancer comprising administering CDX-3379 and a PD-1 inhibitor, wherein the cancer expresses a PIK3CA gene modification, and further given that Huang teaches a mutation in PIK3CA that contributes to the tumorigenicity of a cancer, one of ordinary skill in the art would be able to envision immediately the claimed methods of new claims 33 and 34 directed to a PIK3CA gene mutant at R115. This is because, as stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose (i.e. the mutant of Huang in the modified PIK3CA of Boshoff) renders an invention obvious and an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious.
Response to Arguments
Applicant's arguments filed December 19, 2025 have been fully considered.
Regarding the rejection of the claims under 35 U.S.C. 112(a) for failing to meet the written description requirement, the claims have been amended to include one specific anti-HER3 antibody, and the rejection no longer includes discussion of the anti-HER3 antibody. The PD-1 inhibitor, however, remains undefined, and the rejection is maintained. It is noted that new claims 32 and 34, which list specific PD-1 inhibitors, are not included in the written description rejection. Including these inhibitors in claims 1 and 19 would be sufficient to overcome the rejection under 35 U.S.C. 112(a).
With respect to the rejection of claim under 35 U.S.C. 103, applicant argues that the administration of CDX-3379 with an anti-PD-1 therapy is associated with unexpectedly good synergistic effects, compared to monotherapy (remarks, pg 11). Although it is clear that the combination treatment is better than each treatment alone, it is not clear that the combination treatment is associated with unexpected synergy. An example of unexpected synergy would be a therapeutic response that is significantly greater than the sum of each monotherapy response. However, a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (see MPEP 716.02(a)I).
Applicant asserts that the primary reference Clarke does not teach a method of treating head or neck cancer with CDX-3379 nor do Boshoff, Haratani, and Aktoudianakis remedy this deficiency (remarks, pg 12). Applicant also argues that the properties of CDX-3379 related to epitope binding that induces a conformational lock were not appreciated in the prior art, and that the HER3 antibodies of Clarke, Aktoudianakis, and Haratani do not disclose or suggest these properties (remarks, pg 12). However, Aktoudianakis teaches the antibody CDX-3379 and, thus, teaches all related inherent properties of that antibody. See MPEP 2112.II: There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Applicant’s arguments do not show how the combined teachings of the cited references and the knowledge/skills contained therein cannot render the rejected claims obvious.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675