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 .
Current Status
This action is responsive to the claims of 06/06/2025. Claims 1-17 are pending. Claims 4, 8, and 11 are withdrawn. Claims 1-3, 5-7, 9-10, and 12-17 have been examined on the merits.
Election/Restrictions
Applicant’s election without traverse of a compound of Formula I IRX4204 (below), trastuzumab as the Her2-targeted therapeutic agent, and thyroxine as the thyroid hormone in the reply filed on 06/06/2025 is acknowledged.
IRX4204:
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A search for Applicant’s elected species IRX4204 retrieved prior art, thus the Markush search was not extended to the full scope of Formula (I).
The elected species read on claims 1-3, 5-7, 9-10, and 12-17.
Claims 4, 8, and 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of Her2-targeted therapeutic agent, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/06/2025.
Priority
The effective filing date is 06/11/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/19/2022 (x4), 09/29/2022, and 06/17/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: the chemical structures of Formula (I) and (II) on Pg. 11-12, 27-29, and 31-35 are of low image resolution. Please provide higher resolution images. Appropriate correction is required.
Claim Objections
Claims 1-3, 5-7, 12-13, and 15-16 are objected to because of the following informalities. Appropriate correction is required.
Claims 1 and 5 recite the chemical structure of Formula (I); however, the image resolution is poor. Please provide a higher resolution image to improve readability.
Claims 2-3, 6-7, 12-13, and 15-16 depend from either claim 1 or 5 and do not rectify the above issue. Thus, these claims are similarly objected to.
Claims 1 and 5 recite
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. Please delete the annotated comma as it is unnecessary.
Claims 2-3, 6-7, 12-13, and 15-16 depend from either claim 1 or 5 and do not rectify the above issue. Thus, these claims are similarly objected to.
Claim Interpretation - 35 USC § 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Here, claims 2-3, 6-7, 9-10, 14, and 17 recite the phrase “means for” followed by functional language that does not recite sufficient structure, material, or acts for performing the claimed function.
Claims 2 and 6 recite “means for therapeutically targeting Her2” wherein prong A is met by “means for” and Prong B and C are met by “therapeutically targeting Her2.” The phrase “therapeutically targeting Her2” does not provide any structure to the means for performing this action, i.e., the claim does not recite a chemical structure, name, or class which would be capable of targeting Her2. Thus, the claims, under 35 U.S.C. 112(f), are interpreted as drawn to the corresponding structure recited in the specification and equivalents thereof. The specification defines “means for therapeutically targeting Her2” on Pg. 5 paragraph 21 as mAbs that bind to Her2, antibody-drug conjugates that bind to Her2, and inhibitors of Her2 tyrosine kinase activity.
Claims 3 and 7 recite “means for inhibiting Her2+ tumor cell proliferation” wherein prong A is met by “means for” and Prong B and C are met by “inhibiting Her2+ tumor cell proliferation.” The phrase “inhibiting Her2+ tumor cell proliferation” does not provide any structure to the means for performing this action, i.e., the claim does not recite a chemical structure, name, or class which would be capable of this inhibition. Thus, the claims are interpreted under 35 U.S.C. 112(f). The specification defines “means for inhibiting Her2+ tumor cell proliferation” on Pg. 2-3 paragraph 9 as anti-Her2 antibodies and on Pg. 30 paragraph 109 as an antibody-drug conjugate wherein the antibody is an anti-Her2 antibody.
Claims 9-10, 14, and 17 recite “means for activating RXR/Nurr1 heterodimeric receptors” wherein prong A is met by “means for” and Prong B and C are met by “activating RXR/Nurr1 heterodimeric receptors.” The phrase “activating RXR/Nurr1 heterodimeric receptors” does not provide any structure to the means for performing this action, i.e., the claim does not recite a chemical structure, name, or class which would be capable of this activation. Thus, the claims are interpreted under 35 U.S.C. 112(f). The specification defines “means for activating RXR/Nurr1 heterodimeric receptors” on Pg. 2 paragraph 8 as compounds of Formula I
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and Formula II
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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 5-7, 13, and 15-17 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.
Claim 5 recites the limitation "the Her2 kinase inhibitor" in line 3. There is insufficient antecedent basis for this limitation in the claim. The claim is independent and does not recite “a Her2 kinase inhibitor” at any point in the claim. Thus, it is unclear what Her2 kinase inhibitor the phrase “the Her2 kinase inhibitor” is referring to. The metes and bounds of the claim are therefore undefined rendering the claim indefinite.
Claims 6-7 and 13 are similarly rejected since they depend from claim 5 and do not rectify the underlying issue.
To overcome: replace “the Her2 kinase inhibitor” with “the Her2-targeted therapeutic agent” which has antecedent basis in line 2 of the claim. For purposes of examination, the claim is interpreted as drawn to the Her2-targeted therapeutic agent.
Claims 15-17 each recite the limitation "the inhibition of tumor cell growth by the combination" in line 1-2. There is insufficient antecedent basis for this limitation in the claim. Claims 15-17 depend from claims 1, 5, and 9, respectively, none of which recite inhibition of tumor cell growth or a combination of the claimed drugs. Thus, it is unclear what the inhibition of tumor cell growth and the combination are referring to. The metes and bounds of the claims are therefore undefined rendering the claims indefinite.
To overcome: Applicant may replace "the inhibition of tumor cell growth by the combination" with "
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 1-3, 5-7, 9-10, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over IO (WO 2017/075612, filed in IDS of 06/19/2022) in view of LIBY (Liby, K., et al., Cancer Susceptibility and Prevention, 2007, 13(20), 6237-6243, filed in IDS of 06/19/2022), as evidenced by NCI (National Cancer Institute, NCI Dictionary of Cancer Terms, “Her2/neu,” archived on Wayback Machine 04/23/2008, retrieved from https://web.archive.org/web/20180423100811/https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-neu on 06/23/2025), and MITRI (Mitri, Z., et al., Chemotherapy Research and Practice, 2012, 2012,1-7).
Determining the Scope and Contents of the Prior Art:
IO teaches specific RXR activation by an RXR agonist gives optimal anti-cancer activity when combined with administration of a thyroid hormone (Pg. 2 P5). IO teaches a method of treating breast cancer comprising administering an RXR agonist and a thyroid hormone (Pg. 35 claim 23) wherein the RXR agonist is 3,7-dimethyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid (Pg. 33 claim 3), i.e., IRX4204
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, and the thyroid hormone is thyroxine (Pg. 33 claim 7). IO further teaches the method comprising administration of another anti-cancer agent (Pg. 36 claim 29). IO teaches IRX4204 activated RXR receptors with very high potency with EC50 < 0.5 nM (Pg. 23 Table 1) and selectively activates Nurr1/RXR heterodimer (Pg. 23 P88). IO also teaches IRX4204 inhibited growth of both ER-positive and -negative breast cancer cell lines in vitro with 74% efficacy in the ER-negative cell line (Pg. 26 Table 3).
LIBY teaches NRX194204
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(Pg. 6238 Fig. 1), which is the same compound as IRX4204 as taught by IO, above. LIBY further teaches, in mouse mammary tumor virus (MMTV)-neu mice, NRX194204 not only delayed the development of ER-negative mammary tumors but also caused marked tumor regression (92%) or growth arrest (8%) in all of the mammary tumors when used therapeutically (Pg. 6237 Abstract). LIBY teaches in MMTV-neu mice, wild-type neu is expressed in the mammary tissue under control of the MMTV promotor and ER- mammary tumors begin to appear (Pg. 6240 Right Col. P2). The Examiner understands the neu mammary tumors of LIBY to be an equivalent of HER2+, as evidenced by NCI. NCI discloses HER2/neu is a protein involved in cell growth and is found in breast cancer cells (Line 1). Thus, HER2 and neu are understood to reference the same protein.
MITRI teaches HER2 overexpression is present in approximately 20-30% of breast cancer tumors and is associated with a more aggressive disease, higher recurrence rate, and shortened survival (Pg. 1 Introduction P1). MITRI teaches trastuzumab is the standard of care in treatment of HER2+ breast cancer (Pg. 2 Sect. 3 P1). MITRI further teaches the ideal timing of trastuzumab administration appears to be concurrent with chemotherapy (Pg. 2 Sect. 3 P2). Examiner, thus, understands trastuzumab can be administered with another anti-cancer therapeutic. MITRI also teaches despite the success of Trastuzumab-based therapy in treating all stages of HER2+ breast cancer, resistance to Trastuzumab is an important issue which affects outcomes for a subset of patients (Pg 3 Sect. 5 P1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
IO does not teach the breast cancer is HER2+ or that the additional anti-cancer agent is trastuzumab.
LIBY, evidenced by NCI, does not teach the method of treating HER2+ breast cancer further comprises administration of thyroxine and a HER2-targeted therapeutic such as trastuzumab.
MITRI does not teach a method of treating HER2+ breast cancer by administering IRX4204 and thyroxine.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HER2+ breast cancer and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding treatment of HER2+ breast cancer and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references IO, LIBY evidenced by NCI, and MITRI.
The artisan would be motivated to utilize the method of IO to treat HER2+ breast cancer in order to improve treatment outcomes and cause marked tumor regression or tumor growth arrest in the patient, in view of LIBY and MITRI. The artisan would recognize IRX4204/NRX194204 as suitable for treatment of HER2+ breast cancer since LIBY teaches 92% marked tumor regression and 8% growth arrest in a HER2/neu mouse model of breast cancer (Pg. 6237 Abstract). The artisan would be further motivated to treat HER2+ patients since MITRI teaches HER2+ breast cancer is associated with more aggressive disease (Pg. 1 Introduction P1); thus, the artisan would recognize the need for an improved treatment and in view of IO and LIBY be motivated to treat the HER2+ breast cancer with the combination IRX4204 and thyroxine. Moreover, IO teaches IRX4204 treats both ER-positive and -negative breast cancer cell lines with 74% efficacy in the ER-negative cell line (Pg. 26 Table 3). Thus, the artisan would recognize the efficacy of IRX4204 in treating non-hormone dependent breast cancer, i.e., a group which includes HER2+ breast cancer. Finally, the artisan would be motivated to utilize the combination IRX4204 and thyroxine since IO teaches optimal anti-cancer activity from combination administration of an RXR agonist and thyroid hormone (Pg. 2 P5) wherein thyroxine is preferred (Pg. 33 claim 7).
The artisan would be motivated to utilize this treatment in a patient receiving (instant claims 1 and 9)/undergoing treatment with (instant claim 5) a HER2-targeted therapeutic agent that is trastuzumab since MITRI teaches trastuzumab is the standard of care in treatment of HER2+ breast cancer (Pg. 2 Sect. 3 P1), but a subset of patients experience resistance to trastuzumab therapy (Pg 3 Sect. 5 P1). Thus, the artisan would recognize the need for an additional effective treatment in the case of “less than a complete response” (instant claim 5) to trastuzumab. The artisan would have an expectation of success since IO teaches the IRX4204/thyroxine treatment may be administered with another anti-cancer agent (Pg. 36 claim 29) and MITRI teaches the ideal timing of trastuzumab administration is concurrent with chemotherapy (Pg. 2 Sect. 3 P2).
Moreover, the artisan would have been imbued with at least a reasonable expectation of success that by combining IRX4204 and thyroxine with trastuzumab, one would have achieved a composition useful for treating HER2+ breast cancer since both are taught by the prior art as suitable for such treatment (see all teachings above). See In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two agents each of which is taught by the prior art to be useful for the very same purpose. The idea of combining the two agents flows logically from having been individually taught in the prior art.
Thus, the artisan would find the instant claims 1-3, 5-7, 9-10, and 12-14 obvious.
Claims 1, 5, 9, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over IO (WO 2017/075612, filed in IDS of 06/19/2022), LIBY (Liby, K., et al., Cancer Susceptibility and Prevention, 2007, 13(20), 6237-6243, filed in IDS of 06/19/2022), as evidenced by NCI (National Cancer Institute, NCI Dictionary of Cancer Terms, “Her2/neu,” archived on Wayback Machine 04/23/2008, retrieved from https://web.archive.org/web/20180423100811/https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-neu on 06/23/2025), and MITRI (Mitri, Z., et al., Chemotherapy Research and Practice, 2012, 2012,1-7) as applied to claims 1, 5, and 9 above, and further in view of ROMOND (Romond, E.H., et al., N. Engl. J. Med., 2005, 353(16), 1673-1684).
Determining the Scope and Contents of the Prior Art:
IO, LIBY evidenced by NCI, and MITRI teach the limitations of claims 1, 5, and 9, see above 103 rejection, paragraph 25.
LIBY teaches doses of 30 and 60 mg/kg diet for IRX4204 (Pg. 6242 Table 2).
ROMOND teaches trastuzumab is dosed at 2-4 mg/kg of body weight when administered with another chemotherapy (Pg. 1675 Left Col. P2) to patients with HER2+ breast cancer (Pg. 1673 Abstract Background).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
IO, LIBY evidenced by NCI, and MITRI do not teach the combination treatment of IRX4204 and trastuzumab is synergistic.
ROMOND does not teach the compound of Formula (I).
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HER2+ breast cancer and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding treatment of HER2+ breast cancer and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references IO, LIBY evidenced by NCI, MITRI, and ROMOND.
The claims 15-17 recite the combination of the HER2-targeteted therapeutic and the RXR agonist of Formula (I) results in greater inhibition of tumor growth compared to the additive effects of each of the agents alone. The Examiner understands these claims as being drawn to synergism between the two agents when co-administered.
Thus, the claims 15-17 are drawn to properties of the claimed combination treatment, i.e., the combined administration of the compound of Formula (I) and the HER2-targeted therapeutic agent is synergistic in nature. MPEP 2112.01.II states: “‘Products of identical chemical composition cannot have mutually exclusive properties.’ In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Since the references applied to claims 1, 5, and 9, above, teach both IRX4204 and trastuzumab and their suitability in treatment of HER2+ breast cancer, and the combination treatment of the two is found to be obvious, it would be expected that the combination would have the same physical properties as the combination in the instant application, namely that the combination exhibits synergy.
Furthermore, the Examiner understands this synergy to be a product of the dosages at which the two agents are given. See, for example, Pg. 36 paragraph 145 and Pg. 37 Table 1 of the instant specification, wherein certain concentrations of the two agents, when used together, were synergistic. The determination of the optimum dosages for both IRX4204 and trastuzumab would have been well within the practice of the artisan. The artisan would be motivated to optimize the dosages using the teachings of LIBY and ROMOND as starting points.
MPEP 2144.05(II)(A) provides guidance about the obviousness of optimization of variables within prior art conditions or through routine experimentation: "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).”
In the instant case, the dosages of IRX4204 and trastuzumab are analogous to the “concentration or temperature” recited in the MPEP since dosage is a result-effective variable, i.e. a variable that achieves a recognized result (e.g., treatment outcomes or %inhibition of tumor growth). Since LIBY teaches dosages of IRX4204 that result in regression and arrest of growth in a percentage of HER2+ tumors (Pg.6237 Abstract) and ROMOND teaches doses of trastuzumab in co-administration with another anti-cancer agent to treat HER2+ breast cancer (Pg. 1675 Left. Col. P2), the artisan would have been motivated to modify the dosages of IRX4204 and trastuzumab taught in these prior art references, so as to optimize the treatment outcomes from co-administration of these two agents. Therefore, the dosages that would provide synergistic inhibition of tumor growth would have been obvious to arrive at through routine experimentation. Furthermore, absent any evidence demonstrating a patentable difference from the prior art teachings and the criticality of any dosage that would impart synergy to the combination treatment, the determination of the optimum synergistic dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 5-6, 9, and 12-17 are rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,224,583. Although the claims at issue are not identical, they are not patentably distinct from each other.
Note: withdrawn claims 4, 8, and 11 would be rejected if not withdrawn. Further, the instant application is a CON of the application from which the reference Patent issued, thus, the safe harbor protection of 35 U.S.C. 121 does not apply.
Patent ‘583 claim 5 is drawn to a method of treating a patient with HER2+ breast cancer comprising administering the RXR agonist
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, i.e., IRX4204, and a small molecule HER2 kinase inhibitor including lapatinib (claim 6), neratinib (claim 7), and tucatinib (claim 8). The recited species are species of the instant claims 1-2, 9, 12, and 14 and Patent claim 1 is also anticipatory in view of these species recited in Patent claims 5-8. Patent claim 3 is drawn to the method of treatment further comprising administering thyroid hormone. Patent claim 9 is drawn to the method of treatment wherein the inhibition of tumor cell growth by the combination of the HER2 kinase inhibitor and the RXR agonist is greater than additive effects of each of the HER2 kinase inhibitor and the RXR agonist alone. In view of the recited species, Patent claim 3 is anticipatory of instant claims 12 and 14 and Patent claim 9 is anticipatory of instant claims 15 and 17.
Patent ‘583 claim 12 is drawn to a method of treating a patient with HER2+ breast cancer undergoing treatment with a small molecule HER2 kinase inhibitor wherein there is less than a complete response, comprising continuing treatment with the HER2 kinase inhibitor and initiating treatment with the RXR agonist IRX4204. Patent claims 13, 14, and 15 recite the HER2 kinase inhibitor is lapatinib, neratinib, and tucatinib, respectively. The recited species are species of instant claims 5-6, 13, and 16 and Patent claim 2 is also anticipatory in view of these species recited in Patent claims 12-15. Patent claim 10 is drawn to the method of treatment further comprising administering thyroid hormone. Patent claim 16 is drawn to the method of treatment wherein the inhibition of tumor cell growth by the combination of the HER2 kinase inhibitor and the RXR agonist is greater than additive effects of each of the HER2 kinase inhibitor and the RXR agonist alone. In view of the recited species, Patent claim 10 is anticipatory of instant claim 13 and Patent claim 16 is anticipatory of instant claim 16.
Claims 1-3, 5-7, 9-10, and 12-17 are rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 1 of U.S. Patent No. 10,966,950. Although the claims at issue are not identical, they are not patentably distinct from each other.
Note: The instant application is a CON of application no. 17/123,347 (Patent 11,224,583) which was a DIV of application no. 16/898,230 (Patent 10,966,950). Since the instant application is one step removed from the divisional filing status (i.e., the instant app is not a DIV), the safe harbor protection of 35 U.S.C. 121 does not apply.
Patent ‘950 claims are drawn to a method of treating a patient with HER2+ breast cancer receiving a HER2-targeted therapeutic antibody comprising administering the RXR agonist IRX4204 (claims 1, 5-6, and 9) further comprising administration of the HER2-targeted therapeutic antibody (claim 2) and a thyroid hormone (claim 4); wherein the therapeutic antibody is trastuzumab (claim 7) or pertuzumab (claim 8). Patent ‘950 claim 16 is drawn to the method of treatment wherein the inhibition of tumor cell growth by the combination of the HER2-targeted antibody and the RXR agonist is greater than the additive effects of the two agents alone. The Patent ‘950 recites species of the instant claims (i.e., IRX4204 and trastuzumab/pertuzumab) within the same method of treating HER2+ breast cancer. Thus, the Patent claims 1-2, 4-9, and 16 anticipate the instant claims 1-3, 9-10, 12, 14-15, and 17.
Patent ‘950 claims 3, 10-15, and 17 mirror the limitations of Patent claims 1-2, 4-9, and 16, except that the method of treatment comprises treating a patient undergoing treatment with a HER2-targeted antibody wherein there is evidence of therapeutic effect that is less than a complete response, comprising continuing treatment with the HER2 antibody and initiating treatment with the RXR agonist IRX4204 (see patent claims 3 and 13). Since the Patent claims recite species of the instant claims (i.e., IRX4204 and trastuzumab/pertuzumab) within the same method of treating HER2+ breast cancer with “less than a complete response,” the Patent claims 3, 10-15, and 17 anticipate the instant claims 5-7, 13, and 16.
Claims 1-3, 5-7, 9-10, and 12-17 are rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,998,521. Although the claims at issue are not identical, they are not patentably distinct from each other.
Note: withdrawn claims 4, 8, and 11 would be rejected if not withdrawn.
Patent ‘521 is drawn to a method of treating a patient with HER2+ breast cancer (claim 11) resistant to at least one HER2-targetted therapeutic agent, comprising administering the RXR agonist IRX4204 (claim 4) further comprising administering thyroid hormone (claim 3); wherein the HER2-targeted therapeutic agent is an anti-HER2 antibody (claim 5) such as trastuzumab or pertuzumab (claim 6), an antibody-drug conjugate (claim 7), or a HER2 kinase inhibitor (claim 8) chosen from a handful of examples including lapatinib (claims 9-10). Patent ‘521 claim 12 is drawn to the method wherein inhibition of tumor cell growth by the combination RXR and HER2-targeted therapeutic is greater than additive inhibitor effects of each alone. The recited species are species of the rejected instant claims and, thus, anticipate them. Patent claims 1-2 are also anticipatory in view of the above species.
Patent ‘521 claims 13-23 are drawn to the same species as the patent claims 1-12, but the method is drawn to treatment of a patient with HER2+ breast cancer (claim 22) wherein the patient is undergoing treatment with a HER2-targeted therapeutic agent and the cancer has become resistant to the HER2 therapeutic (claim 13).
The examiner understands resistance to the HER2 therapeutic to be indicative of “less than a complete response” (see instant claim 5). Thus, since species of the instant are recited in the same treatment context, the Patent claims anticipate the instant claims.
Claims 1-3, 5-7, 9-10, and 12-17 are provisionally rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claim 1-20 of copending Application No. 18/649,476 (reference application, claims of 04/29/2024). Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims are drawn to a method of treating HER2+ breast cancer (claim 9) comprising administering the RXR agonist IRX4204 (claim 3) wherein the cancer is resistant to at least one HER2-targeted therapeutic and the patient is receiving the HER2-targeted therapeutic (parent claim 1); wherein the HER2-targeteted therapeutic agent is an anti-HER2 antibody (claim 4) such as trastuzumab or pertuzumab (claim 5), an antibody-drug conjugate comprising an anti-HER2 antibody (claim 6), or a HER2 kinase inhibitor (claim 7) chosen from a handful including lapatinib (claim 8). Reference claim 10 is drawn to the method wherein inhibition of tumor cell growth by the combination RXR and HER2-targeted therapeutic is greater than additive inhibitor effects of each alone. The recited species are species of the rejected instant claims and, thus, anticipate them. The examiner understands resistance to the HER2 therapeutic to be indicative of “less than a complete response” (see instant claim 5).
Reference claims 11-20 are drawn to the same species as the reference claims 1-10, but the method is drawn to treatment of a patient with HER2+ breast cancer (claim 19) wherein the patient is undergoing treatment with a HER2-targeted therapeutic agent and the cancer has become resistant to the HER2 therapeutic (claim 11).
Thus, since species of the instant are recited in the same treatment context, the Reference claims anticipate the instant claims.
Claims 1-3, 5-7, 9-10, and 12-14 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 4-5, 9, and 11 of U.S. Patent No. 11,896,558 in view of MITRI (Mitri, Z., et al., Chemotherapy Research and Practice, 2012, 2012,1-7) as applied to claims 1-3, 5-7, 9-10, and 12-14 in the above 103 rejection.
Determining the Scope and Contents of the Prior Art:
Patent ‘558 claims are drawn to a method of treating a HER2+ cancer in a patient (claim 1) comprising administering the RXR agonist IRX4204 (claim 5) further comprising administering thyroid hormone (claim 4); wherein the HER2+ cancer is breast cancer (claim 9). Patent ‘558 claim 11 is drawn to the method of patent claim 1 further comprising administration of an additional anticancer agent.
The teachings MITRI are above in paragraph 25.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
Patent ‘558 does not teach wherein the additional anticancer agent is a HER2-targeted therapeutic such as trastuzumab, wherein there is evidence of therapeutic effects that is less than a complete response in a patient receiving the trastuzumab.
MITRI is not a U.S. Patent document.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HER2+ breast cancer and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding treatment of HER2+ breast cancer and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent 11,896,558 and MITRI.
The main motivation to treat a patient that is receiving trastuzumab and may have “less than a complete response” to the trastuzumab therapy comes from MITRI: trastuzumab is the standard of care in treatment of HER2+ breast cancer (Pg. 2 Sect. 3 P1), but a subset of patients experience resistance to trastuzumab therapy (Pg 3 Sect. 5 P1). The artisan would have an expectation of success since Patent ‘558 discloses the compound IRX4204 and thyroid hormone may be administered with an additional anti-cancer agent in a method of treating HER2+ breast cancer (see all teachings above).
Claims 1-3, 5-7, 9-10, and 12-14 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 6, 8-10, and 15 of U.S. Patent No. 10,973,788 in view of IO (WO 2017/075612, cited in IDS of 06/19/2022), LIBY (Liby, K., et al., Cancer Susceptibility and Prevention, 2007, 13(20), 6237-6243), as evidenced by NCI (National Cancer Institute, NCI Dictionary of Cancer Terms, “Her2/neu,” archived on Wayback Machine 04/23/2008, retrieved from https://web.archive.org/web/20180423100811/https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-neu on 06/23/2025), and MITRI (Mitri, Z., et al., Chemotherapy Research and Practice, 2012, 2012,1-7) as applied to claims 1-3, 5-7, 9-10, and 12-14 in the above 103 rejection.
Determining the Scope and Contents of the Prior Art:
Patent ‘788 claims are drawn to a method of treating cancer in a patient comprising administering the RXR agonist IRX4204 (claim 1 and 15) further comprising treating the patient with an anti-cancer agent (claim 6) that is a monoclonal antibody (claim 8) and a TSH modulating agent (claim 9) that is a thyroid hormone (claim 10).
The disclosure of Patent ‘788 is referred to in order to understand what cancers are treated by the claimed method, in accordance with MPEP 804(II)(B)(1): “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).” The disclosure Example 4 teaches VTP194204 (i.e., IRX4204) exhibited tumor growth inhibitory effects in breast cancer (Pg. 23 Col. 27 Ex. 4).
The IO, LIBY evidenced by NCI, and MITRI teachings are above, paragraph 25.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
Patent ‘788 does not teach wherein the breast cancer is HER2+, the additional anticancer agent monoclonal antibody is trastuzumab, there is evidence of therapeutic effect that is less than a complete response in a patient receiving the trastuzumab, and the thyroid hormone is thyroxine.
IO, LIBY evidenced by NCI, and MITRI are not U.S. Patent documents.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HER2+ breast cancer and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding treatment of HER2+ breast cancer and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent 10,973,788, IO, LIBY evidenced by NCI, and MITRI.
Since Patent ‘788 teaches the administration of IRX4204 to a patient having breast cancer further comprising administration of an additional anti-cancer agent and a thyroid hormone, i.e., the same context in which IRX4204 is taught to be useful by IO, the artisan would find the instant claims obvious and be motivated to practice the instant method by the same logic as laid out in the above 103 rejection, paragraph 25.
The main motivation, with an expectation of success to include thyroxine as the thyroid hormone comes from IO: RXR activation by an RXR agonist gives optimal anti-cancer activity when combined with administration of a thyroid hormone (Pg. 2 P5) and the thyroid hormone is thyroxine (Pg. 33 claim 7).
The artisan would be motivated with an expectation of success to treat HER2+ breast cancer in view of LIBY: IRX4204 delayed the development of tumors, caused marked tumor regression (92%), and growth arrest (8%) in a mouse model of HER2/neu breast cancer (Pg. 6237 Abstract).
The main motivation, with an expectation of success, to treat a patient that is receiving trastuzumab and may have “less than a complete response” to the trastuzumab therapy comes from MITRI: trastuzumab is the standard of care in treatment of HER2+ breast cancer (Pg. 2 Sect. 3 P1), but a subset of patients experience resistance to trastuzumab therapy (Pg 3 Sect. 5 P1).
Claims 1-3, 5-7, 9-10, and 12-14 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 6, and 10 of U.S. Patent No. 9,655,872 in view of IO (WO 2017/075612, filed in IDS of 06/19/2022), LIBY (Liby, K., et al., Cancer Susceptibility and Prevention, 2007, 13(20), 6237-6243, filed in IDS of 06/19/2022), as evidenced by NCI (National Cancer Institute, NCI Dictionary of Cancer Terms, “Her2/neu,” archived on Wayback Machine 04/23/2008, retrieved from https://web.archive.org/web/20180423100811/https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-neu on 06/23/2025), and MITRI (Mitri, Z., et al., Chemotherapy Research and Practice, 2012, 2012,1-7) as applied to claims 1-3, 5-7, 9-10, and 12-14 in the above 103 rejection.
Determining the Scope and Contents of the Prior Art:
Patent ‘872 claims are drawn to a method of treating breast cancer in a patient comprising administering the RXR agonist IRX4204 (claim 1 and 10) further comprising treating the patient with at least one other agent selected from anti-cancer agents and TSH modulating agents (claim 6).
The IO, LIBY evidenced by NCI, and MITRI teachings are above, paragraph 25.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
Patent ‘872 does not teach wherein the breast cancer is HER2+, the additional anticancer agent is a HER2-targeted therapeutic trastuzumab, there is evidence of therapeutic effect that is less than a complete response in a patient receiving the trastuzumab, and the TSH modulator is thyroxine.
IO, LIBY evidenced by NCI, and MITRI are not U.S. Patent documents.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HER2+ breast cancer and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding treatment of HER2+ breast cancer and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent 9,655,872, IO, LIBY evidenced by NCI, and MITRI.
Since Patent ‘872 teaches the administration of IRX4204 to a patient having breast cancer further comprising administration of additional anti-cancer agents and TSH modulators, i.e., the same context in which IRX4204 is taught to be useful by IO, the artisan would find the instant claims obvious and be motivated to practice the instant method by the same logic as laid out in the above 103 rejection, paragraph 25.
The main motivation, with an expectation of success to include thyroxine as the TSH modulator comes from IO: RXR activation by an RXR agonist gives optimal anti-cancer activity when combined with administration of a thyroid hormone (Pg. 2 P5) and the thyroid hormone is thyroxine (Pg. 33 claim 7).
The artisan would be motivated with an expectation of success to treat HER2+ breast cancer in view of LIBY: IRX4204 delayed the development of tumors, caused marked tumor regression (92%), and growth arrest (8%) in a mouse model of HER2/neu breast cancer (Pg. 6237 Abstract).
The main motivation, with an expectation of success, to treat a patient that is receiving trastuzumab and may have “less than a complete response” to the trastuzumab therapy comes from MITRI: trastuzumab is the standard of care in treatment of HER2+ breast cancer (Pg. 2 Sect. 3 P1), but a subset of patients experience resistance to trastuzumab therapy (Pg 3 Sect. 5 P1).
Conclusion
Claims 1-3, 5-7, 9-10, and 12-17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA ELIZABETH BELL whose telephone number is (703)756-5372. The examiner can normally be reached Monday-Friday 8:30-5:00.
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