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 .
DETAILED ACTION
Claims 1-3 are pending and under consideration.
Priority
It is acknowledged that this application is a continuation-in-part application of U.S. Patent Appl. No. 16/494,102 filed September 13, 2019, which is the US National phase of International Patent Application No. PCT/CU2018/050001, filed March 18, 2018, which claims the benefit of priority to Cuban Patent Appl. No. CU 2017-0028, filed March 15, 2017.
Certified copies of foreign priority application (CU 2017-0028) has been received in Application No. 16/494,102.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of May 14, 2024 for claims 1-3 because the claims as currently constituted recite a method of treating pancreas or colorectal carcinoma have activating mutations in RAS with a claimed bivalent vaccine. However, Examples 10-13 of the instant specification, which provide adequate support or enablement of the instantly claimed method, were absent in the prior-filed applications. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
Information Disclosure Statement
The Information Disclosure Statements filed on 08/13/2024 and 08/13/2024 have been considered and entered by examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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 1-3 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 1 recites “whether the patient diagnosed with the carcinoma of the lung is likely to respond or not to …”, which renders the claim indefinite, because claim 1 is drawn to a method for treating a patient with carcinoma of the pancreas or colorectal carcinoma.
Claims 2 and 3 are also rejected because they depend on claim 1.
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 are rejected under 35 U.S.C. 103 as being unpatentable over Lindberg (Lindberg et al., Neoplasia, (2014) 16, 562-571, Publication Year: 2014) in view of Sanchez Ramirez (Sanchez Ramirez et al., EP 3028714 A1, Publication Date: 2016-06-08, cited in IDS).
Lindberg teaches that activating mutations of KRAS have been reported in 75% to 95% of PDAC and the importance of this oncogene in pancreatic tumorigenesis has been demonstrated in mouse model. Developing strategies to target RAS pathway signaling has been emphasized for pancreatic cancer research (page 563, col. 1, para. 1).
Lindberg teaches that the epidermal growth factor receptor (EFGR) and HER2 have also been identified as promising target for PDAC treatment because EGFR and HER2 are overexpressing in many PDAC patients and associated with worse patient outcomes (page 563, col. 1, para. 2). As evidenced by paragraph [0003] of the instant publication US 2024/0299518 A1, EGFR is the same as HER1.
Lindberg teaches that the genetic heterogeneity, signaling redundancy and plasticity of pancreatic tumor cells suggest that monotherapy or signal pathway treatment strategies are unlikely to result in significant and durable responses (page 563, col. 1, para. 3).
Lindberg teaches MEK1/2 inhibitor trametinib, anti-EGFR (anti-HER1) antibody panitumumab, and anti-HER2 antibody trastuzumab and pertuzumab (§ Materials and Methods – MEK1.2 Inhibitor, EGFR/HER2 Inhibitor, and Antibodies)
Lindberg teaches that panitumumab and trastuzumab inhibit the EGF-dependent activation of EGFR (HER1) and HER2 (page 564, col. 2, para. 2).
Lindberg teaches that in KRAS mutant cell line, addition of EGF results in a 50% increase in pERK. Addition of both antibodies to trametinib treatment effectively blocked the EGF-dependent activation of pERK levels (page 564, col. 2, para. 3).
Lindberg teaches that tumor 608 has KRAS mutation and high expression of HER1 and HER2 (see Table 1).
Lindberg teaches that tumor 608 showed statistically significant decrease in growth rate with triple therapy of trametinib + panitumumab + trastuzumab, compared to monotherapies or double therapies (Fig. 3C and Fig. 3D).
Lindberg teaches that triple therapy of trametinib + panitumumab + trastuzumab is effective to another KRAS mutant model: T366 (Table 1, Fig. 3A and Fig. 3B).
Lindberg teaches that the results underscore the importance of therapeutic intervention in both the KRAS-RAF-MEK-ERK and EGFR-HER2 pathways to achieve maximal therapeutic efficacy in vivo (the last paragraph of the article).
Lindberg teaches as set forth above. Lindberg does not explicitly teach the bivalent vaccine (BV) for treatment and the step of determining the presence of activating mutation in RAS.
Sanchez Ramirez teaches adjuvant of very small size proteoliposomes (VSSP) derived from the outer membrane proteins of Neisseria meningitidis, which is capable of activating dendritic cells and polarizing the immune response towards the pattern of T-Helper Type 1 response. See [0011]. Vaccine compositions comprise an immunological adjuvant comprising VSSP formed by the association of the GM3 gangliosides N-acetylated, with the outer membrane protein complex of bacterium Neisseria meningitidis. See [0013].
Sanchez Ramirez teaches that a vaccine composition comprising the ECDs of Her1 and Her2 receptors or fragments thereof in the same proportion and very small size proteoliposomes derived from proteins of the outer membrane of Neisseria meningitidis and GM3 (VSSP-GM3) to induce an immune response against malignant tumors that express HER1 and HER2 receptors, See claim 1.
Sanchez Ramirez teaches a method for treating patients suffering from a disease caused by tumors that express HER1 and HER2 comprising the subcutaneous administration of a vaccine composition of the ECDs of HER1 and HER2 and VSSPs-GM3, See [0018], Fig. 6, and Table 2.
Sanchez Ramirez teaches that in a preferred embodiment the tumor comprises epithelial origin tumors, and more particularly, head and neck, breast, lung, colon, pancreas, See [0025].
Sanchez Ramirez teaches that the decrease in Her1 phosphorylation caused by the immune sera induced by Bivalent Vaccine Her1+Her2 with respect to PI serum was 11.2 times. When the same analysis was performed to the sera induced by monovalent vaccine Her1, the decrease of Her1 phosphorylation was 1.7 times. In the case of sera from the Monovalent Vaccine Her2 group the decrease was 2.2 times. In the case of Her2, the decrease of Her2 phosphorylation induced by sera from mice immunized with Her1+Her2 Bivalent Vaccine with respect to PI serum was 8.7 times. When the same analysis was performed to the sera induced by monovalent vaccine Her1, the decrease in Her2 phosphorylation was 1.7 times, and for the sera from the Monovalent Vaccine Her2 group the decrease was 3.5 times (Figure 4). See Example 4.
Sanchez Ramirez teaches that active therapy with cancer vaccine has emerged as a new therapeutic option whose aim is to activate the immune system response in patients with tumors that express HER1 and HER2 ([0011]).
It would have been prima facie obvious to one of ordinarily skilled in the art before the effective date the invention was filed to have modified and combined the methods taught by Lindberg and Sanchez Ramirez, and to replace the anti-HER1 antibody and anti-HER2 antibody (taught by Lindberg) with the bivalent vaccine (taught by Sanchez Ramirez), and to add a step to check the presence of KRAS activating mutations. One of ordinary skill in the art would have had a reasonable expectation of success, because Lindberg and Sanchez Ramirez teach:1) MEK1/2 inhibitor + anti-HER1 antibody + anti-HER2 antibody can achieve the maximal antitumor activity in pancreatic cancer with KRAS mutation and high HER1 and HER 2 expressions (e.g. tumor 608); 2) bivalent vaccine can lead to inhibition both HER1 and HER 2 in vivo; 3) the vaccine therapy represents new active therapy which can activate the immune system response in patients; 4) the bivalent vaccine shows anti-tumor activity for various cancers. Given that the method of determining the presence of KRAS activating mutations are well known in the art, as evidenced by Lindberg, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. The incentive/motivation for implementing the step is to identify the patient population which is more suitable for the BV therapy and to expand the options for treating such population.
Regarding claim 2, Sanchez Ramirez teaches that for use in inducing an immune response in a treatment administered subcutaneously every two weeks to complete a total of 5 doses and subsequently monthly as maintenance dose for at least one year, See claim 8. One of ordinary skill would have known to use the well-known administration regimen for this BV in the treatment. It is also noted that optimal suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[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). See MPEP 2144.05(II)(A).
Regarding claim 3, the responses recited are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, “complete or partial response after the administration of 9 doses of the BV” are given no weight. Lindberg and Sanchez Ramirez teach the same method as claim 1, thus, the same treatment outcomes would have been expected.
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 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No.: US7,776,342 B2 (thereafter Pat. 342, Publication Date: 2010-08-17, cited in IDS), in view of Lindberg (Lindberg et al., Neoplasia, (2014) 16, 562-571) and Sanchez Ramirez (Sanchez Ramirez et al., EP 3028714 A1, Publication Date: 2016-06-08, cited in IDS).
Claims 1-3 are rendered obvious by the combined teachings of the prior art above as discussed in the 103 section, the 103 being incorporated here. The addition of the patented claims of the reference patent over related subject matter only further supports this obviousness.
The claims of Pat. 342 teach a composition, comprising: immunogenic antigens, including extracellular domains of HER1 and HER2: an immunogenic potentiating (VSSPs) effective amount of a vaccine carrier consisting of very small size proteoliposomes (VSSPs) derived from the Outer Membrane Protein Complex (OMPC) of Neisseria meningitidis, wherein the ganglioside GM3 has been incorporated into the OMPC (claims 1-9).
The claims of Pat. 342 do not explicitly teach using the compound to treat a patient with carcinoma of the pancreas or colorectal carcinoma and the step of determining whether a patient diagnosed with cancer is likely to respond to treatment with the inhibitor, comprising a step to determine the presence activating mutations in RAS, or dosage and administration of the BV composition.
Lindberg and Sanchez Ramirez the method of instant claims 1-3 as set forth above.
Patent. 342, Lindberg and Sanchez Ramirez are considered to be analogous to the present invention as they are in the same field of anti-HER1/anti-HER2 therapy for cancers. The claims of Pat. 342 teach a composition of bivalent vaccine comprising the extracellular domains of HER1 and HER2 receptors. It would have prima facie been obvious to one of ordinarily skilled in the art before the time the invention was filed to use the BV of the claims of Pat. 342 for treating carcinoma of pancreas having activating mutations in RAS with a composition comprising the BV taught by the claims of Pat. 342, and to add a step to check the presence of KRAS activating mutations as taught by Lindberg and Sanchez Ramirez. One of ordinary skill in the art would have had a reasonable expectation of success, because Lindberg and Sanchez Ramirez teach:1) MEK1/2 inhibitor + anti-HER1 antibody + anti-HER2 antibody can achieve the maximal antitumor activity in pancreatic cancer with KRAS mutation and high HER1 and HER 2 expressions (e.g. tumor 608); 2) bivalent vaccine can lead to inhibition both HER1 and HER 2 in vivo; 3) the vaccine therapy represents new active therapy which can activate the immune system response in patients; 4) the bivalent vaccine shows anti-tumor activity for various cancers. Given that the method of determining the presence of KRAS activating mutations are well known in the art, as evidenced by Lindberg, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. The incentive/motivation for implementing the step is to identify the patient population, which is more suitable for the BV therapy, and expand the options for treating such population.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
