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 .
Priority
The present application, filed on 03/29/2024, is a 371 of National Stage of International Application No. PCT/KR2022/006317, filed on 05/03/2022, and claims benefit of U.S. Provisional Application No. 63/183,869, filed on 05/04/2021.
Applicant cannot rely upon the certified copy of the foreign priority application to provide priority for the claims because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Examiner is unable to determine whether the content of this instant application is supported in the original disclosure provided in the provisional application, thus examined claims 1-5 and 7-9 have an effective filing date of 10/06/2023.
Information Disclosure Statement
Three Information Disclosure Statement(s) (IDSs), filed on 10/06/2023, 07/07/2025, and 03/13/2026, are acknowledged and considered. One reference is stricken for the reasons detailed herein. Foreign reference Cite No. 4, The Henry M. Jackson Foundation for the Advancement of Military Medicine, INC., listed in IDS filed on 10/06/2023, is not provided.
Claim Status
Claims 1-5 and 7-9 are pending. Claim 6 is canceled. Claims 1-5 and 7-9 are examined herein below.
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 1-5 and 7-9 is 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 1 is indefinite because it fails to incorporate specific criteria/parameters and/or distinct steps to carry out the “method for predicting reactivity” and for “examining immunogenicity.” Thus, a skilled artisan would not be able to determine, with a reasonable degree of certainty, how to perform the method and/or implement the instant limitation(s) to make and use the claimed invention. Therefore, the metes and bounds of the claim cannot be ascertained.
Regarding claim 9, though the instant Specification indicates that “the less immunogenicity against HER2-ICD antigen before vaccination…the more favorable the enhancement of immunogenicity and securement of long-term immunogenicity by vaccination (instant Specification pg. 14, lines 16 -22)” and “it is preferable to select a patient group with low to almost no immunogenicity against HER2-ICD antigen at baseline (instant Specification pg. 13, lines 22-24),” the claim language in the instant claim fails to clearly and precisely define the metes and bounds of the claimed invention because it fails to incorporate specific criteria/parameters and/or distinct steps to actively perform the “method for selecting a patient to be administered” and fails to define a successful selection, thus a skilled artisan would not be able to determine, with a reasonable degree of certainty, how perform the method and/or implement the instant limitation(s) to make and use the claimed invention.
Claims 2-5 and 7-8 are rejected as being dependent on rejected independent claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to an abstract mental process and a law of nature without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101
(see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the
claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e.,
mathematical concepts, certain methods of organizing human activity such as a fundamental
economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application
(see MPEP § 2106.05(a)-(c), (e)-(h)). Only if a claim
(1) recites a judicial exception and
(2) does not integrate that exception into a practical application, do we then look
to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the
claimed judicial exception into a patent-eligible application of the judicial exception.
Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider
whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-
understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A
JUDICIALEXCEPTION
Step 2A, Prong 1
Claim 1 recites “predicting reactivity” and “examining immunogenicity against HER2-ICD antigen in peripheral blood mononuclear cells (PBMCs),” which the specification clarifies involves exposing PMBCs isolated from a subject to a HER2-ICD antigen, prompting PMBCs (immune cells) to activate, multiply, and produce/secrete HER2-ICD antigen-specific IFN-γ (instant Spec, pg. 6, lines 18-31 and pg. 7, lines 1-9; pg. 23, lines 13-14), are drawn to observing a natural relationship/correlation and are directed to an abstract mental process and a law of nature or natural phenomenon.
Claim 2 recites “patient to be vaccinated…is a cancer patient expressing HER2,” which the instant Specification clarifies “HER2 overexpression is observed in 15-30% of all breast cancer patients (instant Spec pg. 2, lines 23-24) and “patient…includes breast cancer patients or breast cancer patients expressing HER2 (instant Spec pg. 8, lines 2-4),” is drawn to identifying/detecting presence of a specific biomarker correlated to a disease state, which is directed to a law of nature.
Claim 9 recites “selecting a patient,” which the instant Specification suggests involves examining the immunogenicity of PMBCs isolated from a patient before vaccination and determining level of immune response at baseline (instant Specification pg. 13, lines 22-24), which is directed to an abstract mental process.
Step 2A, Prong 2
The judicial exceptions are not integrated into a practical application because the additional elements of “selecting a patient to be administered (claim 9)” is an insignificant extra-solution activity, namely a data-gathering step performed to observe a result and that does not add a meaningful limitation to the judicial exceptions.
Further, the judicial exceptions are not integrated into a practical application because the additional elements of “the patient…is a cancer patient expressing HER2 (claim 2),” and “the patient…has no experience with HER2-directed therapy (claim 3)” are insignificant extra-solution activities, namely data-gathering steps or preliminary steps that are incidental to observing the result or natural correlation (phenomenon)/law of nature and performing the abstract mental process that do not add any meaningful limitations to integrate the judicial exceptions into a practical application.
ELIGIBILITY STEP 2B: WHETHER ADDITIONAL ELEMENTS AMOUNT TO
SIGNIFICANTLY MORE THAN THE JUDICIAL EXCEPTION (INVENTIVE CONCEPT)
Step 2B
The instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the method/technique for examining/evaluating immunogenicity against a HER2-ICD antigen in PBMCs isolated from a subject to predict reactivity to the vaccine as recited in the claimed invention, which the instant Specification clarifies involves measuring the amount of HER2-ICD antigen-specific IFN-γ produced using enzyme-linked immune-spot assay (ELISPOT) [instant Specification, pg. 6, lines 24-26; pg. 7, lines 9-14], Applicant discloses is a routine method/technique known in the art (instant Specification, pg. 20, lines 11-15). Additionally, Applicant cites prior art to support that the ELISPOT method/technique is known and conventional for measuring immune response in PBMCs from a patient to evaluate immunogenicity as recited in the instant claim (see Disis et al., J Clin Oncol, 2009, 27, 28, 4685-4692 as suggested in instant Specification, pg. 20, lines 11-15, provided in IDS filed 07/07/2025, referenced as NPL Cite No. 13).
Further, the instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the HER2-ICD-directed therapeutic composition comprising a therapeutic antibody (claim 4), specifically trastuzumab (claim 5), is known and well-understood and lacks an unconventional combination. For example, Arribas Lopez teaches and suggests a HER2-ICD-directed therapeutic composition comprising a therapeutic antibody, specifically Herceptin®, the brand name for trastuzumab (see Arribas Lopez et al., US 2009/0311262 A1: para 0065).
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.
Claim(s) 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Joubert et al., (Joubert et al., Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics, 2016, PLoS ONE, 11, 8, e0159328, 1-22), in view of Salazar et al., (Salazar et al., A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer, 2009, Journal of Clinical Oncology, 27, 15_suppl, Abstract 3054), as evidenced by Omabe et al., (Omabe et al., HER2-Specific Vaccines for HER2-Positive Breast Cancer Immunotherapy, 2015, World Journal of Vaccines, 5, 106-128, provided in IDS filed on 10/06/2023, referenced as NPL Cite No. 10 ).
Throughout the article, Joubert teaches a method or tool for predicting the immunogenicity of biotherapeutic attributes by examining peripheral blood mononuclear cells (PBMCs) from healthy subjects with no experience or exposure to the therapeutic attributes. Joubert further teaches monitoring PBMCs for T-cell proliferation, number of IFN-γ secreting cells, and secreted cytokine concentration. In one embodiment, Joubert teaches assessing the relative risk of immunogenicity in the clinic, by exposing PBMCs to ten biotherapeutic monoclonal antibodies, including Herceptin®, to evaluate their ability to illicit an immune response in the PBMCs. Responses of PBMCs are compared to observed rate of clinical immunogenicity for most of the respective antibodies. Joubert teaches that relative response of PBMC to biotherapeutic antibody agrees with the respective observed clinical immunogenicity and correlated with rate of observed clinical immunogenicity (Joubert et al., 2016, PLoS ONE, 11, 8, e0159328, 1-22). Joubert further teaches this method or tool can be applied to selection of candidate to be administered the biotherapeutic and/or evaluation of attributes that may affect risk of immunogenicity (Joubert et al., 2016, PLoS ONE, 11, 8, e0159328, pg. 16, last full para).
Regarding claim 1, Joubert teaches determining reactivity of a biotherapeutic, comprising examining immunogenicity against selected antigens in peripheral blood mononuclear cells (PBMCs) of patients to be treated with a biotherapeutic, before treatment (Joubert et al., Joubert et al., 2016, PLoS ONE, 11, 8, e0159328, pg. 1, Abstract; pg. 2, full para 2; pg. 5, full paras 4-5 and continue to top of pg. 6; pg. 7, Table 1; pg. 7, "Results" and continue to pg. 8). Joubert does not teach determining immunogenicity of a HER2-ICD DNA vaccine.
Throughout abstract, Salazar teaches a HER2-ICD DNA-based vaccine for vaccinating patients with stage III and IV HER2-positive (+) breast cancer in complete remission. Salazar teaches immunization with the HER2-ICD DNA-based vaccine was determined to be safe and to illicit the desired immune response in the phase I clinical trial. Salazar further teaches that HER2+ cancer patients developed immunity to the HER2 ICD.
Salazar teaches, a HER2-ICD DNA vaccine (Salazar et al., Abstrac2009, Journal of Clinical Oncology, 27, 15_suppl, Abstract).
It would have been prima facie obvious, at the time of filing, to combine the method of determining reactivity of a biotherapeutic comprising examining immunogenicity against selected antigens in PMBCs of subjects before treatment, as taught by Joubert, with the teachings of Salazar in order to substitute the biotherapeutic with the HER2-ICD (intracellular) DNA vaccine, as taught by Salazar. A skilled artisan would have been motivated to combine the teachings of Joubert and Salazar to make a simple substitution for the HER2-ICD DNA vaccine because it would enable selection of appropriate subjects that can be vaccinated and enable evaluation of attributes that may impact risk of immunogenicity of the vaccine (see Joubert et al., 2016, PLoS One, 11, 8, e0159328, pg. 16, last full para). In the art, it is known that HER2 overexpression occurs in 20%-30% of breast cancers and progression of the cancer for patients on HER2-specific immunotherapy relies on HER2 signaling and downstream pathways. The art also teaches that some HER2-directed treatments, while effective for breast cancer treatment, are not long-lasting as patients develop resistance to the treatment. Thus the development of an alternative, effective HER2 treatment, such as DNA-based vaccines, while challenging, is urgently needed (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 108, full para 1). Further, in the art, it is known that HER2 DNA vaccines offer distinct advantages over other vaccine types which include increased stability, lower cost, and ease of purification in large yields (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 109, full para 1). Thus, a skilled artisan would have been further motivated to combine the teachings of Joubert and Salazar to predict the reactivity of a HER2-ICD DNA-based vaccine because it would enable development of an alternative, effective, lower cost, stable HER2-directed DNA vaccine for treatment of HER2-positive cancer urgently needed at the time of filing. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining known teachings to make a simple substitution between known components/elements, with known functions, would yield expected and predictable results.
Regarding claim 2, Joubert and Salazar teach all the limitation of claim 1. Salazar further teaches wherein the patient to be vaccinated with the HER2 vaccine is a cancer patient expressing HER2 (Salazar et al., Abstrac2009, Journal of Clinical Oncology, 27, 15_suppl, Abstract, “Methods”).
It would have been prima facie obvious, at the time of filing, to combine the method of determining reactivity of a biotherapeutic, as taught by Joubert, with the teachings of a HER2-ICD DNA vaccine for the treatment of HER2-positive (+) breast cancer, as taught by Salazar. In the art, it is known that HER2 overexpression occurs in 20%-30% of breast cancers and progression of the cancer for patients on HER2-specific immunotherapy relies on HER2 signaling and downstream pathways. The art also teaches that some HER2-directed treatments, while effective for HER2+ breast cancer treatment, are not long-lasting as patients eventually develop resistance to the treatment. Consequently, alternative and effective HER2-directed treatment for HER+ breast cancer is urgently needed (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 108, full para 1). Thus, a skilled artisan would have been motivated to combine the teachings of Joubert and Salazar to vaccinate patients expressing HER2 because it would enable development of an urgently needed alternative, effective, lower cost, stable HER2-directed treatment for patients with HER2+ breast cancer. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these known teachings of known components/elements would yield expected and predictable results.
Claim(s) 3 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Joubert et al., (Joubert et al., Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics, 2016, PLoS One, 11, 8, e0159328, 1-22), in view of Salazar et al., (Salazar et al., A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer, 2009, Journal of Clinical Oncology, 27, 15_suppl, Abstract 3054), as applied to claims 1-2 above, and further in view of Knutson et al., (Knutson et al., Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients, 2001, J. Clin. Invest., 107, 477–484), as evidenced by Disis et al., (Disis et al., Concurrent Trastuzumab and HER2/neu-Specific Vaccination in Patients With Metastatic Breast Cancer, 2009, J Clin Oncol, 27, 28, 4685-4692, provided in IDS filed 07/07/2025, referenced as NPL Cite No. 13), and Omabe et al., (Omabe et al., HER2-Specific Vaccines for HER2-Positive Breast Cancer Immunotherapy, 2015, World Journal of Vaccines, 5, 106-128, provided in IDS filed on 10/06/2023, referenced as NPL Cite No. 10).
Regarding claim 3, the teachings of Joubert and Salazar are discussed herein above. Joubert and Salazar teach all the limitation of claims 1-2. Joubert and Salazar do not teach the patient to be vaccinated has no experience with HER2-directed therapy before vaccination.
Throughout the article, Knutson teaches a study wherein active immunization with HER2 helper peptide epitopes generate CD4 and CD8 T-cell peptide and protein responses. Knutson teaches the goal is to develop vaccination strategies that prevent disease rather not treat disease. Knutson teaches nineteen cancer patients with HER-2 overexpression received a HER-2/neu peptide–based vaccine preparation composed of HER2-neu helper peptides. Knutson further teaches most patients generated viral-like levels of peptide-specific precursors to HER-2/neu HLA-A2 peptides and developed persistent peptide-specific T-cell precursors. Knutson teaches that some of the patient selection criteria included (1) stage III/IV breast or ovarian cancer that was treated with standard treatments at the time which consisted of chemotherapy, radiation therapy, or combined modality and (2) HER2 overexpression in the primary tumor or metastasis. Disis confirms that the for clinical trial referenced in this Knutson reference, vaccinated patients did not have a history of HER2-directed therapy, such as trastuzumab (see ref. 1 in Disis et al., 2009, J Clin Oncol, 27, 28, and Disis et al., 2009, J Clin Oncol, 27, 28, pg. 4690 last para- continue to top of pg. 4691).
Knutson teaches the limitation(s) of claim 3 reciting wherein the patient to be vaccinated with the HER2 vaccine has no experience with HER2-directed therapy before vaccination (Knutson et al., 2001, J. Clin. Invest., 107, pg. 478, “Methods”).
It would have been prima facie obvious, at the time of filing, to combine the method for predicting the reactivity of a biotherapeutic, as taught by Joubert, in view of Salazar, with the selection criteria of no prior HER2-directed therapy for the patient to be vaccinated, as taught by Knutson. In the art, it is known that HER2-directed treatment such as Herceptin®, the brand name for trastuzumab, while effective for treating advanced HER2+ breast cancer, is not long-lasting as patients eventually develop resistance to the treatment (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 108, full para 1). A skilled artisan would have been motivated to combine these teachings and incorporate the patient selection criteria of no prior HER2-directed therapy before vaccination because it would increase the likelihood that the patient to be vaccinated would not be resistant to, or develop resistance during or shortly after, the HER2 DNA-based vaccine treatment. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known prior art elements, according to known methods, to yield expected and predictable results.
Regarding claim 9, Joubert and Salazar teach all the limitations of claim 1. Joubert and Salazar do not teach a method for selecting a patient to be vaccinated.
Regarding claim 9, given the indefiniteness of the claim language, see 35 U.S.C. 112b rejection herein above, using the broadest reasonable interpretation and in light of the specification, Knutson reads on the limitation(s) of the instant claim reciting a method for selecting a patient to be administered with a HER2 vaccine, by the method of claim 1 (Knutson et al., 2001, J. Clin. Invest., 107, pg. 478, "Methods").
A skilled artisan would have been motivated to combine the method of predicting reactivity to a biotherapeutic, as taught by Joubert, in view of Salazar, with the patient selection criteria and method taught by Knutson. A skilled artisan would have been motivated to combine these teachings because selection of the optimal patient to be vaccinated would enable proper evaluation of vaccine safety and prediction of reactivity or immunogenicity elicited by the HER2-ICD DNA vaccine in patients diagnosed with a specific stage of cancer (see Knutson et al. and Joubert et al.). At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these known teachings of known components/elements would yield expected and predictable results.
Claim(s) 4-5 and 7 are rejected under 35 U.S.C. as being unpatentable over Joubert et al., (Joubert et al., Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics, 2016, PLoS One, 11, 8, e0159328, 1-22), in view of Salazar et al., (Salazar et al., A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer, 2009, Journal of Clinical Oncology, 27, 15_suppl, Abstract 3054), and Knutson et al., (Knutson et al., Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients, 2001, J. Clin. Invest., 107, 477–484), as applied to claims 1-3 above, further in view of Arribas Lopez et al., (US 2009/0311262 A1, Pub. Date: 12/17/2009), as evidenced by Norell et al., (Norell et al., Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial, 2010, Journal of Translational Medicine, 8, 53, 1-11), and Omabe et al., (Omabe et al., HER2-Specific Vaccines for HER2-Positive Breast Cancer Immunotherapy, 2015, World Journal of Vaccines, 5, 106-128).
Regarding claims 4-5, the teachings of Joubert, Salazar, and Knutson are discussed herein above. Joubert and Salazar teach all the limitations of claim 1, Salazar further teaches the limitation(s) of claim 3, and Knutson further teaches claim 3. Joubert, Salazar, and Knutson do not a HER2-directed therapeutic composition comprising an antibody against HER2, which comprises trastuzumab.
Throughout the disclosure, Arribas Lopez teaches a method diagnosing and treating cancers expressing HER2. Arribas Lopez teaches antibodies, or their fragments thereof, that recognize an epitope of a truncated form of HER2, including HER2-ICD domain, referenced as SEQ ID NO:1 in the Arribas Lopez disclosure in a patient sample (see sequence details herein below). Arribas Lopez further teaches an embodiment wherein antibodies disclosed in the claimed invention are used in pharmaceutical compositions for the treatment of cancers in which HER2-ICD, having a sequence referred to as SEQ ID NO:1 in the Arribas Lopez disclosure, is expressed and combined with pharmaceutically acceptable vehicles or excipients and at least one antibody such as Herceptin® , the brand name for trastuzumab.
Arribas Lopez teaches the limitation(s) of claims 4-5 reciting wherein the HER2-directed therapy is by a pharmaceutical composition comprising a therapeutic antibody against HER2 (claim 4) [US 2009/0311262 A1: paras 0020-0022 and 0065] and , wherein the therapeutic antibody against HER2 comprises trastuzumab, referred to by the brand name Herceptin TM (claim 5) [US 2009/0311262 A1: para 0065].
It would have been prima facie obvious, at the time of filing, to combine the teachings of Joubert, in view of Salazar and Knutson, with the method and HER2-ICD-directed vaccine composition taught by Arribas Lopez. The prior art teaches HER2 vaccination in combination with an antibody against HER2, trastuzumab, increases effectiveness of treatment relative to each treatment alone (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 120). Further, in the art, it has been shown that a cohort of patients for whom trastuzumab (anti-HER2 antibody) treatment was ineffective, when HER2-DNA vaccination is combined with trastuzumab treatment the DNA vaccine potentiates trastuzumab. In the art, it is taught that the trastuzumab antibody may synergize with specific T-cells, produced as an immune response to HER2 DNA-based vaccination, which motivates a skilled artisan to combine trastuzumab (antibody) with HER2 in a vaccine composition (see Norell et al., Journal of Translational Medicine, 8, 53, pg. 2, full paras 1-2; pg. 7, full para 3; and pg. 9, full para 3). Further, Arribas Lopez explicitly teaches and suggests a HER2-ICD-directed therapy with a pharmaceutical composition comprising an antibody against HER2, specifically Herceptin TM, the brand name for trastuzumab. Thus, a skilled artisan would have been motivated to combine the teachings of Joubert, in view of Salazar and Knutson, with the teachings of Arribas Lopez because it would yield a more effective DNA-based alternative vaccine treatment for HER2+ cancers that is more stable and cost effective. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these known teachings, known to perform the same function separately as they do when combined, would yield expected and predictable results.
Regarding claim 7, Joubert and Salazar teach all the limitations of claim 1. Salazar further teaches wherein the HER2- ICD DNA vaccine comprises a plasmid vector encoding a HER2-ICD domain (Salazar et al., Journal of Clinical Oncology, 27, 15_suppl, Abstract 3054). Joubert and Salazar do not teach a HER2-ICD domain having the sequence of SEQ ID NO: 2.
Arribas Lopez teaches the limitation(s) of claims 7 reciting a nucleotide sequence encoding a HER2-ICD domain and having the sequence of SEQ ID NO: 2 (US 2009/0311262 A1: Abstract; paras 0032, 0051, 0065). Further, Arribas Lopez teaches a HER2-ICD domain having a sequence referred to SEQ ID NO: 1 in Arribas Lopez et al. that has 99.8% sequence identity/similarity with instant claim SEQ ID NO:2. See details below (full sequence alignment is not shown).
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It would have been prima facie obvious, at the time of filing, to combine the method of predicting reactivity of a biotherapeutic, as taught by Joubert, in view of Salazar, with the teachings of a nucleotide sequence encoding HER2-ICD DNA having SEQ ID NO:2 recited in the instant claim, as taught by Arribas Lopez. In the art, it is known that HER2 overexpression occurs in 20%-30% of breast cancers and progression of the cancer for patients on HER2-specific immunotherapy relies on HER2 signaling and downstream pathways. The art also teaches that some HER2-directed treatments, while effective for breast cancer treatment, are not long-lasting as patients develop resistance to the treatment. Thus the development of an alternative, effective HER2 treatment, while challenging, is urgently needed (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 108, full para 1). Arribas Lopez explicitly teaches and suggests a pharmaceutical composition for the treatment of HER2+ cancer composed of expression of HER2-ICD having a nucleotide sequence of SEQ ID NO:2, which is referred to as SEQ ID NO:1 in the disclosure taught by Arribas Lopez (see Arribas Lopez et al., US 2009/0311262 A1: para 0065). Thus, a skilled artisan would have been motivated to combine these teachings because it would enable development of an alternative and more effective HER2-ICD-directed vaccine urgently needed for treatment of HER2+ cancers. Additionally, it is known that HER2 DNA-based vaccines offer distinct advantages over other vaccine types which include increased stability, lower cost, and ease of purification in large yields (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 109, full para 1). Thus, a skilled artisan would have been further motivated to combine these teachings to arrive at the claimed DNA-based vaccine composition because of the increased stability, lower cost, easily purifiable DNA-based vaccine. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these known teachings of known components/elements, known to perform the same functions separately as they do when combined, to arrive at the pharmaceutical composition recited in the claimed invention, would yield expected and predictable results.
Claim(s) 8 is rejected under 35 U.S.C. 103 as being unpatentable over Joubert et al., (Joubert et al., Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics, 2016, PLoS One, 11, 8, e0159328, 1-22), in view of Salazar et al., (Salazar et al., A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer, 2009, Journal of Clinical Oncology, 27, 15_suppl, Abstract 3054), , and Arribas Lopez et al., (US 2009/0311262 A1, Pub. Date: 12/17/2009), as applied to claims 1 and 7 above, further in view of Erickson et al., (Patent No.: US 6,632,979 B2, Patent Date: 10/14/2003), as evidenced by Omabe et al., (Omabe et al., HER2-Specific Vaccines for HER2-Positive Breast Cancer Immunotherapy, 2015, World Journal of Vaccines, 5, 106-128), and Ladjemi et al., (Ladjemi et al., Anti-HER2 vaccines: new prospects for breast cancer therapy, 2010, Cancer Immunol Immunother, 59, 1295-1312).
Regarding claim 8, the teachings of Joubert, Salazar, and Arribas Lopez are discussed herein above. Joubert and Salazar teach all the limitations of claim 1 and Salazar and Arribas Lopez teach the limitation(s) of claim 7. Joubert, Salazar and Arribas Lopez do not teach a HER2-ICD domain having the sequence of SEQ ID NO: 3.
Throughout the disclosure, Erickson teaches a HER2-transgenic nonhuman tumor model that overexpresses HER2 at comparable levels to HER2-positive human patients that respond poorly to Herceptin®. Erickson teaches nonhuman tumor models that are designed to test drug candidates for the treatment of HER2-overexpressing cancers that do not respond to or respond poorly to current treatments, such as Herceptin®. Erickson further teaches pharmaceutical compositions comprising anti-cancer molecules identifiable in the nonhuman models and other assays combined with at least one antibody and a pharmaceutically acceptable carrier.
Erickson teaches the limitation(s) of claim 8 reciting , wherein the HER2-ICD domain having the nucleotide sequence of SEQ ID NO: 3 (US 6,632,979 B2: col 5, lines 15-21; after col. 36, pgs. 69 (bottom)-73). Further, Erickson teaches a HER2-ICD domain having a sequence referred to SEQ ID NO: 1 in Erickson et al. that has 99.8% sequence identity/similarity with instant claim SEQ ID NO:3 (US 6,632,979 B2: after col. 36, pgs. 69 (bottom)-73). See sequence details and alignment herein below (full sequence alignment is not shown). Throughout the disclosure Erickson uses terms “ErbB2,” “c-erb-B2,” and “HER2” interchangeably.
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It would have been prima facie obvious, at the time of filing, to combine the teachings of Joubert, in view of Salazar and Arribas Lopez, with the teachings of Erickson in order to substitute with a HER2-ICD having the sequence of SEQ ID NO:3 as recited in the instant claim, and referred to as SEQ ID NO:1 in the referenced disclosure, as taught by Erickson. In the art, it is known that 85% of HER2+ cancer patients do not respond or respond poorly to Herceptin®, creating an urgent clinical need to develop alternative HER2-directed therapies (Erickson et al., US 6,632,979 B2: col 2, lines 60-67- col 3, lines 1-5). The prior art further teaches that a HER2-ICD receptor having SEQ ID NO:3, as recited in the instant claim and referred to as SEQ ID NO:1 in Erickson et al., is overexpressed in a nonhuman model used to find therapeutic candidates that function by specifically binding to the recited HER2-ICD overexpressed on the surface of tumor cells in the model (Erickson et al, US 6,632,979 B2: col 2, lines 60-67- col 3, lines 1-5, col 4, lines 46-67, col. 5, lines 8-12, col. 5, lines 15-17, Fig. 1). Further, in the art, it is known that development of anti-HER2 vaccines was motivated by observations of immune responses to HER2-overexpressing tumors in HER2+ cancer patients (see Ladjemi et al., 2010, Cancer Immunol Immunother, 59, pg. 1296, full para 1 and Table 1). Additionally, it is known that HER2 DNA-based vaccines offer distinct advantages over other vaccine types which include increased stability, lower cost, and ease of purification in large yields (see Omabe et al., 2015, World Journal of Vaccines, 5, pg. 109, full para 1). Thus, a skilled artisan would have been motivated to combine these teachings to develop a HER2-ICD DNA-based vaccine comprising a HER2-ICD sequence having SEQ ID NO:3, as recited in the instant claim and referred to as SEQ ID NO:1 in the disclosure taught by Erickson, shown to be overexpressed on tumor cells, as an immune-stimulating antigen in an alternative, effective, stable, and inexpensive HER2-ICD DNA-based therapy to treat HER2+ cancer, that was urgently needed at the time of filing. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining known teachings to make a simple substitution between known components/elements, with known functions, would yield expected and predictable results.
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 2 and 7-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-13 and 19 of copending Application No. 18/292,905 in view of Erickson et al., (Patent No.: US 6,632,979 B2, Patent Date: 10/14/2003).
Claims 11-13 and 19 in reference copending application 905’ recites all the limitations of instant claims 2 and 7-8 but narrowly discloses wherein the subject is a gastric cancer patient and further recites the vaccine composition comprising a pharmaceutically acceptable carrier.
The teachings of Erickson are discussed herein above.
Erickson, in the same field of endeavor, recites the disease or disorder to be treated by HER2-directed treatment is cancer with HER2-expressing cells including, but not limited to, carcinoma, lymphoma, blastoma, sarcoma, lung cancer, breast cancer, ovarian cancer, gastric or stomach cancer, and vulval cancer (US 6,632,979 B2: col 25, lines 20-51).
It would be prima facie obvious to combine the teachings of reference copending application 905’ claims 11-13 and 19 with the teachings of Erickson. A skilled artisan would have been motivated to combine these teachings because it would enable the development of a HER2-DNA vaccine to treat a broader range of HER2+ cancers. A skilled artisan would have a reasonable expectation of success because combining these teachings amounts to combining known elements/teachings, according to known methods, to yield expected and predictable results.
Erickson further recites HER2-directed therapeutic compositions and/or formulations comprising antibodies and/or an optional pharmaceutically acceptable carrier (US 6,632,979 B2: col 5, lines 8-12 and col 24, lines 18-33).
The limitation in reference claim 19 of copending application 905’ reciting the vaccine composition comprising a pharmaceutically acceptable carrier is an obvious variation of the claimed invention as recited in instant claims 2 and 7-8 because it would be prima facie obvious to combine the teachings of reference copending application 905’ claims 11-13 and 19 with the teachings of HER2-directed therapeutic compositions taught and suggested by Erickson. A skilled artisan would have been motivated to combine these teachings because it would function as an inactive, non-toxic vehicle or delivery agent that would safely transport an active pharmaceutical ingredient to its target site within the body, optimizing drug release, stability, and bioavailability (see Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980) by incorporation by Erickson et al., US 6,632,979 B2: col 24, lines 18-33 ). A skilled artisan would have a reasonable expectation of success because combining these teachings amounts to combining known components/elements according to known methods, and each known to perform the same functions separately as they do when combined, would yield expected and predictable results.
This is a provisional nonstatutory double patenting rejection.
Conclusion
All examined claims (1-5 and 7-9) are rejected. No claims are allowed.
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/MELISSA LIZETTE LIRIANO-NG/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 15, 2026
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