DETAILED ACTION
Claims 1-8 are currently pending and under examination in the instant application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
Those sections of Title 35, US code, not included in this action can be found in a previous office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/14/24 is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statement has been considered by the examiner, and an initialed and signed copy of the 1449 is attached to this action.
Claim Interpretation
It is noted that the phrase “light smokers” has been defined in the specification as an individuals who smoke during at most 25 years, including patients who did not stop smoking but started less than 25 years or cumulated less than 25 years smoking in their life (Specification, page 8, lines 33-37).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kotsakis et al. (2014) Lung Cancer, Vol. 86, 59-66, as evidenced by Georgoulias et al. (2013) Clinical Lung Cancer, Vol. 14 (4), 461-465.
Kotsakis et al. teaches method of treating non small cell lung cancer (NSCLC) in HLA-A*0201 positive patients by peptide vaccination comprising two subcutaneous injections of the cryptic TERT572Y peptide (Vx-001) followed by four injections of native TERT572 peptide with a three week interval between vaccinations (Kotsakis et al., pages 59-62). Kotsakis et al. teaches that the patients received prior chemotherapy and/or radiotherapy, and that the patients included males, patients over 65 years of age, and patients with non-squamous or squamous NSCLC (Kotsakis et al., page 62, Table 2). Kotsakis et al. further teaches testing CTL obtained from the blood of patients pre-vaccination in an IFN-gamma ELISpot assay to determine immunological response to the native TERT572 peptide (Kotsakis et al., pages 62-63, Figure 1). Figure 1 of Kotsakis et al. shows no response from the patients CTL to the native TERT572 peptide prior to vaccination. Further, Kotsakis et al. shows that the patients with no immunological response to native TERT572 were responsive to vaccination with the cryptic 572Y peptide and to later vaccination with the native TERT572 peptide. Kotsakis et al. also demonstrates the development of an immunological response to TERT572 post vaccination with the cryptic TERT572Y peptide which increased after additional vaccination with the native TERT572 peptide, and a statistically significant increase in survival following peptide vaccination in both patients with stable disease and progressive disease pre-vaccination (Kotsakis et al., pages 63-64, Figure 1 and 2, and Tables 3 and 4).
In regards to the sequence of the cryptic TERT572Y (Vx-001) peptide and the native TERT572 peptide, while Kotsakis et al. does not provide the sequence of these peptides, Georgoulias et al. provides evidence that the sequences of the cryptic TERT572Y (Vx-001) peptide and the native TERT572 peptide are 100% identical to SEQ ID NOS: 2 and 1 respectively. Specifically, Georgoulias et al. teaches that the sequence of TERT572Y is YLFFYRKSV (instant SEQ ID NO:2) and the sequence of TERT572 is RLFFYRKSV (instant SEQ ID NO:1) (Georgoulias et al., page 462). Thus, by teaching all the limitations of the claims as written, Kotsakis et al. anticipates the instant invention as claimed.
Claim Rejections - 35 USC § 103
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kotsakis et al. (2014) Lung Cancer, Vol. 86, 59-66, in view of Georgoulias et al. (2013) Clinical Lung Cancer, Vol. 14 (4), 461-465, and Clinical Trial NCT01935154 (Version 7, submitted December 8, 2015), Clinical Trials.gov, archive, pages 1-11, as evidenced by Gridelli et al. (2020) Brit. J. Canc., https://doi.org/10.1038/s41416-020-0785-y, pages 1-6.
Kotsakis et al. teaches method of treating non small cell lung cancer (NSCLC) in HLA-A*0201 positive patients by peptide vaccination comprising two subcutaneous injections of the cryptic TERT572Y peptide (Vx-001) followed by four injections of native TERT572 peptide with a three week interval between vaccinations (Kotsakis et al., pages 59-62). Kotsakis et al. teaches that the patients received prior chemotherapy and/or radiotherapy, and that the patients included males, patients over 65 years of age, and patients with non-squamous or squamous NSCLC (Kotsakis et al., page 62, Table 2). Kotsakis et al. further teaches testing CTL obtained from the blood of patients pre-vaccination in an IFN-gamma ELISpot assay to determine immunological response to the native TERT572 peptide (Kotsakis et al., pages 62-63, Figure 1). Figure 1 of Kotsakis et al. shows no response from the patients CTL to the native TERT572 peptide prior to vaccination. Further, Kotsakis et al. shows that the patients with no immunological response to native TERT572 were responsive to vaccination with the cryptic 572Y peptide and to later vaccination with the native TERT572 peptide. Kotsakis et al. also demonstrates the development of an immunological response to TERT572 post vaccination with the cryptic TERT572Y peptide which increased after additional vaccination with the native TERT572 peptide, and a statistically significant increase in survival following peptide vaccination in both patients with stable disease and progressive disease pre-vaccination (Kotsakis et al., pages 63-64, Figure 1 and 2, and Tables 3 and 4). Thus, Kotsakis et al. alone provides a reasonable expectation that patients with TERT positive tumors, including non-immunogenic TERT-positive tumors, will at the very least exhibit an increased anti-TERT immune response following vaccination with Vx-001 which translates to significantly increased survival.
In regards to the sequence of the cryptic TERT572Y (Vx-001) peptide and the native TERT572 peptide, while Kotsakis et al. does not provide the sequence of these peptides, Georgoulias et al. teaches that the sequences of the cryptic TERT572Y (Vx-001) peptide and the native TERT572 peptide are 100% identical to SEQ ID NOS: 2 and 1 respectively. Specifically, Georgoulias et al. teaches that the sequence of TERT572Y is YLFFYRKSV (instant SEQ ID NO:2) and the sequence of TERT572 is RLFFYRKSV (instant SEQ ID NO:1) (Georgoulias et al., page 462). Further in regards to the treatment of patients who received platinum based chemotherapy prior to vaccination and who exhibited a response to the chemotherapy prior to vaccination, and the timing of collecting a blood sample for CTL analysis, Georgoulias et al. supplements Kotsakis et al. by describing a similar clinical trial using the same vaccination strategy with TERT572Y and TERT572 for the treatment of NSCLC in patients who have received prior therapy with a platinum based chemotherapeutic. Georgoulias et al. teaches a detailed protocol involving selecting patients for treatment with the TERT572Y and TERT572 peptides within 3 weeks of completion of first line platinum based chemotherapy, where the patients are tested and selected for HLA-A*0201 positivity, TERT positive NSCLC, and stable or progressive disease (Georgoulias et al., pages 463-464). Note that Georgoulias et al., like Kotsakis et al. teaches the treatment of both patients with stable disease and progressive disease following chemotherapy. Georgoulias et al. further teaches additional testing to be completed prior to vaccination to establish a baseline for the trial, including various scans and the testing of blood samples from the patients for immune responses (Georgoulias et al., page 464).
Therefore, based on the teachings of Georgoulias et al. to test for various parameters affecting selection for the clinical trial and to establish baseline values for patients prior to vaccination and within 3 weeks of completion of platinum based chemotherapy, including the testing of blood samples for immune response, it would have been prima facie obvious to the skilled artisan at the time of filing to obtain a blood sample from a patient at any time within 3 weeks, such as 3 days, 1 week, 10 days etc., after completion of platinum based chemotherapy for an NSCLC and to use the blood sample in the IFN-gamma ELISpot methods of testing blood derived CTL for native TERT572 immunogenicity taught by Kotsakis et al. to establish baseline immunity prior to vaccination with TERT572Y and TERT572 for the treatment of NSCLC, where the treatment results in significantly prolonged survival, with a reasonable expectation of success.
Kotsakis et al. in view of Georgoulias et al. further differ from the instant methods of claim 4-5 by not specifically teaching to treat NSCLC in patients who are never smokers with the method set forth in claim 1. The NCT01935154 clinical trial describes a clinical trial that began in 2012 and was first submitted to the NIH database of clinical trials on August 26, 2013. The version cited here is the version submitted on December 8, 2015, which indicates that at that time the study was no longer recruiting participants (NCT01935154, page 2). The NCT01935154 clinical trial was designed to study the efficacy of the Vx001 Vaccine in NSCLC patients where patient selection criteria included HLA-A*0201 positive, TERT positive IV or recurrent stage I-III NSCLC who had received platinum based 1st line chemotherapy and who were classified as CR, PR, or SD (NCT01935154, pages 2-6). Note that while the NCT01935154 clinical trial doesn’t define the components of the Vx001 Vaccine, the Vx001 vaccine comprises the same components- TERT572Y cryptic peptide and the native TERT572 peptide- used by Kotsakis et al. (Kotsakis et al., page 60). Further, while the NCT01935154 clinical trial doesn’t identify the characteristics of the participants enrolled in the study, Gridelli et al. provides the final results of NCT01935154 clinical trial, and provides specific details regarding the characteristics of the enrolled participants including age, sex, histology of the NSCLC, and smoking status of the participants. Although Gridelli et al. is a post-filing reference, it is only relied upon in this rejection as evidence of the characteristics of the participants who were enrolled in the NCT01935154 clinical trial, which had stopped accepting participants as of December 8, 2015. Gridelli et al. states that the participants in this study included males, patients over 65, patients with non-squamous NSCLC, and both never smokers and light smokers (<25 years) (Gridelli et al., page 4, Table I). These characteristics are inherent to these patients. As such, the NCT01935154 clinical trial provides motivation to treat never smokers or light smokers with the Vx001 vaccine.
Therefore, in view of the motivation provided by the NCT01935154 clinical trial to treat never smokers or light smokers with the Vx001 vaccine, it would have been prima facie obvious to the skilled artisan at the time of filing to treat never smokers or light smokers with NSCLC who have received prior therapy with a platinum based chemotherapeutic using the method as taught by Kotsakis et al. in view of Georgoulias et al. with a reasonable expectation of success.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S Patent No. 12,048,737, hereafter referred to as the ‘737 patent.
The ‘737 patent claims are a species of the instant claims. The ‘737 patent claims recite the same limitations as recited in the instant claims with the exception that the ‘737 patent claims include the additional method step of providing a blood sample comprising Cytotoxic T lymphocytes (CTLs) from the patient collected less than 2 weeks after the end of a platinum-based first line chemotherapy and measuring an anti-tumor CTL response, wherein the CTLs in the blood sample have no response specific for the peptide of SEQ ID NO: 1 and/or the peptide of SEQ ID NO: 3 and/or the peptide of SEQ ID No: 5 prior to vaccination. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, the ‘737 application claims 1-12 render instant claims 1-8 obvious.
Claims 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent 8,663,645, hereafter referred to as the ‘645 patent, in view of Georgoulias et al. (2013) Clinical Lung Cancer, Vol. 14 (4), 461-465, Kotsakis et al. (2014) Lung Cancer, Vol. 86, 59-66, Clinical Trial NCT01935154 (Version 7, submitted December 8, 2015), Clinical Trials.gov, archive, pages 1-11, as evidenced by Gridelli et al. (2020) Brit. J. Canc., https://doi.org/10.1038/s41416-020-0785-y, pages 1-6.
The claims of the ‘645 patent recite methods comprising vaccinating patients against a tumor antigen by vaccinating with 2 administration of a cryptic TERT572Y peptide (SEQ ID NO:2) followed by vaccination with 4 administrations of the native TERT572 peptide (SEQ ID NO:1). While the ‘645 patent claims encompass the instant claims, they do not recite the characteristics of the patients vaccinated, the tumor to be treated, or the timing between vaccinations. Georgoulias et al. supplements the ‘645 patent claims by teaching a clinical trial for patients with treating patients with NSCLC with Vx001, which comprises vaccinating with TERT572Y (SEQ ID NO:2) followed by vaccination with TERT572 (SEQ ID NO:1), the exact same methodology as claimed in the ‘645 patent claims. Georgoulias et al. further teaches the treatment of patients who received platinum based chemotherapy prior to vaccination, who further exhibited a response to the chemotherapy prior to vaccination, and who were tested and selected for HLA-A*0201 positivity, TERT positive NSCLC, and stable or progressive disease (Georgoulias et al., pages 463-464). Georgoulias et al. further teaches additional testing to be completed prior to vaccination to establish a baseline for the trial, including various scans and the testing of blood samples from the patients for immune responses (Georgoulias et al., page 464). Kotsakis et al. also teaches the same methodology of treating cancer recited in the ‘645 patent claims. Kotsakis et al. teaches the treatment of non small cell lung cancer (NSCLC) in HLA-A*0201 positive patients by peptide vaccination comprising two subcutaneous injections of the cryptic TERT572Y peptide (Vx-001) followed 3 weeks later by four injections of native TERT572 peptide, where the patients received prior chemotherapy and/or radiotherapy, and the patients included males, patients over 65 years of age, and patients with non-squamous or squamous NSCLC ((Kotsakis et al., pages 59-62, and Table 2). Kotsakis et al. further teaches testing CTL obtained from the blood of patients pre-vaccination in an IFN-gamma ELISpot assay to determine immunological response to the native TERT572 peptide, and shows that the patients with no immunological response to native TERT572 were responsive to vaccination with the cryptic 572Y peptide and to later vaccination with the native TERT572 peptide (Kotsakis et al., pages 62-63, Figure 1). .
Therefore, based on the motivation provided by Georgoulias et al. and Kotsakis et al. provide motivation to treat NSCLC in male patients, patients over 65, patients who have received prior platinum based chemotherapy, and patients with non-squamous NSCLC with the Vx001 vaccine, it would have been obvious to utilize the methodology of the ‘645 patent claims to treat these patient populations with a reasonable expectation of success. Further, based on the teachings of Georgoulias et al. to test for various parameters affecting selection for the clinical trial and to establish baseline values for patients prior to vaccination and within 3 weeks of completion of platinum based chemotherapy, including the testing of blood samples for immune response, it would have been obvious to the skilled artisan at the time of filing to obtain a blood sample from a patient at any time within 3 weeks, such as 3 days, 1 week, 10 days etc., after completion of platinum based chemotherapy for an NSCLC and to use the blood sample in the IFN-gamma ELISpot methods of testing blood derived CTL for native TERT572 immunogenicity taught by Kotsakis et al. to establish baseline immunity prior to vaccination with TERT572Y and TERT572 for the treatment of NSCLC with a reasonable expectation of success.
In regards to the use of the method of the ‘645 patent claims to treat patients who are never smokers or light smokers, the NCT01935154 clinical trial describes a clinical trial that began in 2012 and was first submitted to the NIH database of clinical trials on August 26, 2013. The version cited here is the version submitted on December 8, 2015, which indicates that at that time the study was no longer recruiting participants (NCT01935154, page 2). The NCT01935154 clinical trial was designed to study the efficacy of the Vx001 Vaccine in NSCLC patients where patient selection criteria included HLA-A*0201 positive, TERT positive IV or recurrent stage I-III NSCLC who had received platinum based 1st line chemotherapy and who were classified as CR, PR, or SD (NCT01935154, pages 2-6). Note that while the NCT01935154 clinical trial doesn’t define the components of the Vx001 Vaccine, the Vx001 vaccine comprises the same components- TERT572Y cryptic peptide and the native TERT572 peptide- used by Kotsakis et al. (Kotsakis et al., page 60). Further, while the NCT01935154 clinical trial doesn’t identify the characteristics of the participants enrolled in the study, Gridelli et al. provides the final results of NCT01935154 clinical trial, and provides specific details regarding the characteristics of the enrolled participants including age, sex, histology of the NSCLC, and smoking status of the participants. Although Gridelli et al. is a post-filing reference, it is only relied upon in this rejection as evidence of the characteristics of the participants who were enrolled in the NCT01935154 clinical trial, which had stopped accepting participants as of December 8, 2015. Gridelli et al. states that the participants in this study included males, patients over 65, patients with non-squamous NSCLC, and both never smokers and light smokers (<25 years) (Gridelli et al., page 4, Table I). These characteristics are inherent to these patients. As such, the NCT01935154 clinical trial provides motivation to treat never smokers or light smokers with the Vx001 vaccine.
Therefore, in view of the motivation provided by the NCT01935154 clinical trial to treat never smokers or light smokers with the Vx001 vaccine, it would have been obvious to the skilled artisan at the time of filing to utilize the methodology of the ‘645 patent claims in view of Georgoulias et al. and Kotsakis et al. to treat these patient populations with a reasonable expectation of success.
Claims 1-5 and 7-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-8, and 10-13 of U.S. Patent No. 16/611,172, hereafter referred to as the ‘172 application. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The ‘172 application independent claim 1 are a species of the instant broader claimed methods in that the ‘172 claim 1 is limited to the treatment of lung cancer in never smokers or light smokers. Claims 2-3, 5-8, and 10-13 of the ‘172 recite and encompass the limitations set forth in instant dependent claims 25, and 7-8. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, the ‘172 application claims 1-3, 5-8, and 10-13 render instant claims 1-8 obvious.
No claims are allowed.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/
Primary Examiner, Art Unit 1634
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