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 .
Application Status
The amended claims filed April 1, 2024 are acknowledged. Claims 3-4, 6, 8-9, 11-18, 22-23, 25-26, and 28-29 are amended.
Claims 1-30 are pending and under examination herein.
Specification
The disclosure is objected to because of the following informalities: The brief description of Figure 2 (page 6) recites “Figure 9A” and “Figure 9B”. Only three figures are present in the disclosure.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See page 14. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Applicant may remedy this objection by removing the leading “www.” from each URL.
Note Regarding Claim Interpretation
Claims 26-27 recite comparisons of Galectin-9 levels “relative to a control value”. Regarding the meaning of “a control value”, the specification (page 40, lines 15-18) states the following: “A control level may refer to the level of Galectin-9 in a matched sample of a subject of the same species (e.g., human) who is free of the solid tumor. In some examples, the control
level represents the level of Galectin-9 in healthy subjects. In some embodiments, the control
level may be a baseline level prior to treatment.” This definition will be used when applying prior art.
Claim Objections
Claim 5 is objected to for the following minor informalities: “anti-Galecti-9 antibody” in line 4 should instead be spelled “anti-Galectin-9 antibody”.
Appropriate correction is requested.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5 and 28 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.
Regarding claim 5, the phrase “optionally” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Examples and preferences in a claim may lead to confusion over the intended scope of the claim. The description of examples or preferences is properly set forth in the specification rather than the claims.
Claim 28 recites “the human patient”. There is insufficient antecedent basis for this limitation in the claim. Claim 28 depends from claim 1, which recites “a subject” but does not recite “a human patient” to which the claimed limitation may refer.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
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.
(1)
Claims 1, 3-7, 9, 11, and 15-30 are rejected under 35 U.S.C. 103 as being unpatentable over Koide (WO 2020/223702 A1; earliest priority date: May 1, 2019; cited in IDS; hereafter Koide ‘702).
The applied reference has common inventors (A. Filipovic, E. Elenko) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Koide ‘702 describes methods for treating solid tumors using an anti-Galectin-9 antibody (e.g., Abstract). Pertinent to claims 1, 3-5, and 7, Koide discloses a method for treating a solid tumor (e.g., a metastatic tumor) that comprises administering an anti-Galectin-9 antibody (e.g., G9.2-17 IgG4) comprising three heavy chain CDRs as set forth in SEQ ID NOs: 4-6, respectively, and three light chain CDRs as set forth in SEQ ID NOs: 1-3, respectively (which share 100% sequence identity to the anti-Galectin-9 antibody CDRs recited in claim 1) at a dose of about 1 mg/kg to about 32 mg/kg (e.g., about 4 mg/kg, or about 16 mg/kg) once every two weeks (e.g., pages 2-5, 12-18; claims 1-21). In specific embodiments, the anti-Galectin-9 antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 8 (which share 100% sequence identity to instant SEQ ID NOs: 7 and 8, respectively), relevant to claim 18. The anti-Galectin-9 antibody may comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO: 15 (which share 100% sequence identity to instant SEQ ID NOs: 19 and 15, respectively), wherein said heavy chain comprises the modified IgG4 Fc region set forth in instant SEQ ID NO: 14 (e.g., pages 4-5), relevant to claims 18-22.
Relevant to claim 6, the anti-Galectin-9 antibody is administered once weekly (e.g., page 8 (description of Figure 7), Example 13 at pages 123-125).
Further relevant to claim 1 and to claims 9 and 11, Koide ‘702 teaches that the method of treatment includes another concurrent anti-cancer therapy, e.g., the PD-1 inhibitor tislelizumab, administered at a dose of 200 mg every three weeks by intravenous infusion (e.g., page 4; claims 1 and 8-10).
Relevant to claims 17 and 23-25, Koide ‘702 teaches that the subject (e.g., a human patient) treated in the method of the invention may have previously undergone one or more prior anti-cancer therapies such as chemotherapy or radiotherapy and is resistant to the one or more prior therapies (e.g., page 5). Relevant to claims 26-28, Koide ‘702 teaches that the subject (e.g., human patient) to be treated in a method of the invention has an elevated serum or plasma level of Galectin-9 relative to a control value, or the subject has an elevated level of Galectin-9 expressed on cancer cells and/or immune cells relative to a control value, said control values being based on a value obtained from a healthy human subject (e.g., page 5). Pertinent to claims 29-30, Koide ‘702 further teaches that the treatment methods of the invention may further comprise monitoring occurrence of adverse effects in the subject and reducing the dose of anti-Galectin-9 antibody and/or anti-PD-1 antibody if adverse effects occur (e.g., page 5).
While Koide ‘702 teaches an overall broader range of dosages of anti-Galectin-9 antibody that can be administered (“about 1 mg/kg to about 32 mg/kg”) relative to the instant claims (“about 0.2 mg/kg to about 18 mg/kg”), the claimed range of “about 0.2 mg/kg to about 18 mg/kg” largely overlaps the range described in the prior art. MPEP § 2144.05(II)(A) sets forth, "[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). Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This is because, as is made clear from the prior art, the determination of the dosage regimen of a known drug was well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out a method of treating solid tumors that comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., the G9.2-17 IgG4 antibody, at a dose of about 0.2 mg/kg to about 18 mg/kg) and tislelizumab, based on the teachings of Koide ‘702. The skilled artisan would have been motivated to do so because Koide ‘702 teaches that the combination of G9.2-17 and an anti-PD-1 antibody has a synergistic effect compared to either treatment alone (e.g., Example 1 at pages 73-75; Figure 9). There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of these antibodies individually in the treatment of solid tumors, and because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
Regarding claims 15-16, one of ordinary skill in the art would recognize that there are a finite number of dosing schedules which may be practiced when administering combined therapies. Accordingly, it would be obvious to administer the anti-Galectin-9 antibody and tislelizumab either on the same day or on two consecutive days, with one before the other.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
(2)
Claims 1-2 and 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Koide ‘702 (WO 2020/223702 A1; supra) as applied to claims 1, 3-7, 9, 11, and 15-30 above, and further in view of Koide (WO 2020/223704 A1; earliest priority date: May 1, 2019; cited in IDS; hereafter “Koide ‘704”) and Vanasse (WO 2021/123902 A1; published June 24, 2021).
The applied reference of Koide ‘704 has common inventors (A. Filipovic, E. Elenko) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
The teachings of Koide ‘702 are recited in the 35 U.S.C. § 103 rejection above.
Koide ‘702 does not expressly teach that the solid tumor treated in the method of the invention is head and neck cancer, urothelial cancer, gastric esophageal cancer, or non-small cell lung cancer (NSCLC). Koide ‘702 also does not expressly teach that tislelizumab is administered at a dose of about 300 mg every four weeks.
Koide ‘704 discloses methods for identifying a subject as having certain solid cancers (e.g., non-small cell lung cancer, gastric cancer, esophageal cancer) based on Galectin-9 levels in a biological sample obtained from said patient and further providing treatment for said solid cancer (e.g., Abstract; pages 2-3, 23-24). In particular embodiments, Koide ‘704 describes treatment methods in which an anti-Galectin-9 antibody (e.g., G9.2-17 IgG4, comprising identical CDRs to those recited in claim 1) is administered in combination with a checkpoint inhibitor, e.g., an anti-PD-1 antibody such as tislelizumab (e.g., pages 3-12).
Vanasse describes combination therapies for treating cancerous conditions, which comprise administering a TIM-3 inhibitor (e.g., anti-TIM-3 antibody) and TGF-β inhibitor (e.g., anti-TGF-β antibody), and further comprises a PD-1 inhibitor (e.g., BGB-A317, also known as tislelizumab) (e.g., Abstract; pages 3-5). Vanasse teaches that the anti-TIM-3 antibody (MBG453) partially blocks the interaction of TIM-3/Galectin-9 (e.g., Example 1, pages 150-151; Example 4, pages 152-153). Vanasse discloses that the PD-1 inhibitor is administered intravenously, at a dose of about 200 mg to about 400 mg (e.g., 300 mg) once every three or four weeks (e.g., page 5), relevant to claims 9-14.
Based on the further teachings of Koide ‘704 and Vanasse, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive at a combination treatment method for treating a solid tumor (e.g., NSCLC), wherein an anti-Galectin-9 antibody (e.g., G9.2-17 IgG4) and tislelizumab are co-administered and wherein the tislelizumab is delivered at a dose of about 300 mg every four weeks, through the course of routine optimization. The skilled artisan would have been motivated to do so because Koide ‘704 teaches that the combination of G9.2-17 IgG4 and tislelizumab is likewise suitable for solid tumor cancers including gastric cancer or NSCLC where higher Galectin-9 is observed. There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of these antibodies individually or together in the treatment of solid tumors. In addition, similarly to the anti-Galectin-9 antibody G9.2-17 IgG4 described by Koide ‘702 and ‘704, the treatment method recited by Vanesse likewise targets and prevents the interaction between TIM-3 and its ligand Galectin-9 in addition to inhibiting PD-1.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
(3)
Claims 1-30 are rejected under 35 U.S.C. 103 as being unpatentable over Koide (US 2019/0127472 A1; cited in IDS; hereafter “Koide ‘472”) in view of Vanasse (WO 2021/123902 A1; supra) and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363).
Koide ‘472 describes the use of anti-Galectin-9 antibodies for inhibiting Galectin-9-mediated signaling and treating solid tumors (e.g., Abstract). Pertinent to claims 1-3 and 17-18, Koide ‘472 recites methods of inhibiting Galectin-9-mediated signaling in a subject (e.g., human patient) having a solid tumor (e.g., NSCLC, squamous cell head and neck cancer, and/or a metastatic solid tumor lesion) by administering an anti-Galectin-9 antibody of the invention, e.g., G9.2-17 (which comprises a VH and VL comprising the amino acid sequences of SEQ ID NOs: 55 and 54, respectively, which share 100% sequence identity to the instantly claimed VH/VL recited in claim 18 and their corresponding CDRs), and a PD-1 inhibitor (e.g., ¶ 0004-0033, 0046-0050, 0474). Pertinent to claims 19-22, Koide ‘472 teaches that the anti-Galectin-9 antibody may be either an IgG1 or IgG4 antibody, wherein said antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 316 and a light chain comprising the amino acid sequence of SEQ ID NO: 108 (which share 100% sequence identity to instant SEQ ID NOs: 19 and 15, respectively) and said heavy chain comprises the modified Fc region comprising instant SEQ ID NO: 14 (e.g., ¶ 0033-0040).
Relevant to claims 1, 4-7, and 12-15, Koide ‘472 teaches that the anti-Galectin-9 antibodies may be administered at a range of doses, e.g., “from about any of 0.1 μg/kg to 3 μg/kg to 30 μg/kg to 300 μg/kg to 3 mg/kg, to 30 mg/kg to 100 mg/kg or more”, including 2 mg/kg or 10 mg/kg, and at a dosing frequency such as once every week (e.g., ¶ 0068-0069, 0529-0533, 0603). Relevant to claim 8, Koide ‘472 recites that the anti-Galectin-9 is administered intravenously (e.g., ¶ 0082, 0520-0522).
Relevant to claims 23-25, Koide ‘472 teaches that the anti-Galectin-9 antibody treatment may be administered to a patient who is refractory to previous immunotherapy (i.e., immune checkpoint inhibitor therapy) (e.g., ¶ 0600).
Relevant to claims 26-28, Koide ‘472 further states, “Before, during, and after the administration of the pharmaceutical composition, cancerous cells and/or biomarkers in a subject may be measured in a biological sample, such as blood, serum, plasma, urine, peritoneal fluid, and/or a biopsy from a tissue or organ” (¶ 0506). Koide ‘472 notes that Galectin-9 is significantly increased in cancer cells and in the plasma of patients with advanced melanoma compared to healthy controls, and that several studies illustrate the utility of Galectin-9 as a prognostic marker (¶ 0002, 0484). Given that Galectin-9 is a known prognostic marker, it would be obvious to sample for this biomarker (e.g., in serum or plasma or in cancer cells) in patients to be treated.
However, Koide ‘472 does not expressly teach that the anti-PD-1 inhibitor co-administered in the method of treatment is the antibody tislelizumab, or that the occurrence of adverse effects is monitored in the subject to be treated.
Liu discloses, “Tislelizumab (BGB-A317) is an anti-PD-1 monoclonal antibody that was engineered with a nullified Fc portion of the antibody to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Specifically, anti-PD-1 antibodies that bind FcγRs may mediate crosslinking between PD-1–positive T cells and FcγR-positive macrophages, which could induce macrophages to phagocytose active PD-1–positive T cells and possibly diminish cytolytic destruction of tumor cells. As an antagonist to PD-L1/PD-L2–mediated cell signaling, tislelizumab leads to increased cytokine production and restoration of T-cell activation, resulting in immune-mediated tumor cell death” (Section 3). Liu teaches that tislelizumab has previously shown clinical activity in the treatment of treating previously treated metastatic PD-L1-high urothelial carcinoma (e.g., Abstract). Liu further teaches, “Tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab, potentially due to its differential PD‑1 binding orientation. Tislelizumab demonstrated encouraging efficacy results, long duration of response, and a manageable safety profile across multiple clinical trials in advanced NSCLC” (Abstract).
The teachings of Vanasse, with respect to dosing of tislelizumab in a combination treatment regimen for solid tumors, are recited in the 35 U.S.C. § 103 rejection above. In addition, relevant to claims 29-30, Vanasse recites that dose escalation is conducted to establish the dose of NIS793 (anti-TGF-β agent) to be used in combination with MBG453 (anti-TIM-3 agent) that has the most appropriate benefit-risk based on safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics, taking into consideration the maximum tolerated dose (MTD) estimated to have less than 25% risk of causing a dose-limiting toxicity (DLT) (e.g., Example 11 at pages 158-159). Vanasse states that when two patients experience a DLT in a new cohort, the next cohort will be opened at a lower dose level that satisfies the escalation without overdose control (EWOC) criteria in order to reduce the risk of exposing patients to an overly toxic dose (e.g., pages 158-159).
Based on the further teachings of Liu and Vanasse, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive at a combination treatment method for treating a solid tumor (e.g., NSCLC or head and neck cancer), wherein administration of anti-PD-1 antibody tislelizumab is combined with the anti-Galectin-9 antibody (e.g., G9.2-17 IgG4), and wherein tislelizumab is delivered at a dose of about 300 mg every four weeks as determined through the course of routine optimization. The skilled artisan would have been motivated to do so because Liu teaches that tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab and is engineered in such a way to minimize antibody-dependent phagocytosis. There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of the anti-Galectin-9 antibody and tislelizumab individually or together in the treatment of solid tumors. In addition, similarly to the anti-Galectin-9 antibody G9.2-17 IgG4 described by Koide ‘472, the treatment method recited by Vanesse likewise targets and prevents the interaction between TIM-3 and its ligand Galectin-9 in addition to inhibiting PD-1.
It would have been further obvious to carry out the additional step of reducing the dose of the anti-Galectin-9 antibody and/or tislelizumab if adverse effects were observed when monitoring for DLTs. This is because Vanasse teaches that this practice reduces the risk of exposing patients to an overly toxic dose. Although Vanasse does not expressly recite carrying out this practice for an anti-Galectin-9 antibody or an anti-PD-1 antibody, there would still have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of this practice for reducing DLTs when administering alternative antibodies.
Further regarding the instantly claimed dosing ranges and intervals, MPEP § 2144.05(II)(A) sets forth, "[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). Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This is because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same 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.
(1)
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,450,374 in view of Koide ‘472 (US 2019/0127472 A1; supra), Vanasse (WO 2021/123902 A1; supra), and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363; supra).
The ‘374 reference patent claims methods for inhibiting the activity of Galectin-9 or for treating a solid tumor (upper and lower gastrointestinal cancers, lung cancers, head and neck cancers) in a human subject, comprising the step of administering an anti-Galectin-9 antibody comprising identical heavy chain and light chain CDRs to that recited in claim 1 (e.g., patented claims 1, 7-8, 11, 16-18), relevant to claims 1-2 and 17. Patented claims 2-6 and 12-15 recite that the anti-Galectin-9 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 54 (which share 100% sequence identity to instant SEQ ID NOs: 7 and 8, respectively), and a heavy chain constant region as set forth in SEQ ID NO: 422 (which shares 100% sequence identity to instant SEQ ID NO: 14), relevant to claims 18-21. Patented claims 9-10 and 19-20 recite the step of further administering an anti-PD-1 antibody.
The reference patent does not expressly claim that that the anti-Galectin-9 antibody is administered at a dose of about 0.2 mg/kg to about 18 mg/kg and that the anti-PD-1 antibody (tislelizumab) is administered at a dose of about 200 mg to about 400 mg, each by intravenous infusion. The reference patent also does not expressly claim that the subject to be treated in the methods have undergone one or more prior therapies or have elevated Galectin-9 relative to a control value, nor that the methods further comprise monitoring the occurrence of adverse events. However, these deficiencies are remedied by Koide ‘472, Vanasse, and Liu as taught in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the method of treating solid tumors recited in the reference patent, which comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., at a dose of about 0.2 mg/kg to about 18 mg/kg) and an anti-PD-1 antibody, such that the anti-PD-1 antibody is tislelizumab (e.g., administered at a dose of about 200 mg to about 400 mg), based on the further teachings of Koide ‘472, Vanasse, and Liu. The skilled artisan would have been motivated to do so because Liu teaches that tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab and is engineered in such a way to minimize antibody-dependent phagocytosis. There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of these antibodies individually in the treatment of solid tumors, and because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
(2)
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-34, 36-39, 50-54, and 63-65 of co-pending Application No. 17/598,215 (reference application) in view of Koide ‘472 (US 2019/0127472 A1; supra), Vanasse (WO 2021/123902 A1; supra), and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363; supra).
The ‘215 reference application claims methods comprising the step of administering an anti-Galectin-9 antibody comprising identical CDRs to those set forth in claim 1, and identical VH/VL amino acid sequences to those set forth in claim 18, to a subject having a solid tumor (upper and lower gastrointestinal cancers, lung cancers, head and neck cancers), and further comprising the step of administering and anti-PD-1 antibody (e.g., co-pending claims 32-33, 37-38, 50-51, 53-54, 63-64).
The co-pending reference application does not expressly claim that that the anti-Galectin-9 antibody is administered at a dose of about 0.2 mg/kg to about 18 mg/kg and that the anti-PD-1 antibody (tislelizumab) is administered at a dose of about 200 mg to about 400 mg, each by intravenous infusion. The co-pending reference application also does not expressly claim that the subject to be treated in the methods have undergone one or more prior therapies or have elevated Galectin-9 relative to a control value, nor that the methods further comprise monitoring the occurrence of adverse events. However, these deficiencies are remedied by Koide ‘472, Vanasse, and Liu as taught in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the method of treating solid tumors recited in the co-pending claims, which comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., at a dose of about 0.2 mg/kg to about 18 mg/kg) and an anti-PD-1 antibody, such that the anti-PD-1 antibody is tislelizumab (e.g., administered at a dose of about 200 mg to about 400 mg), based on the further teachings of Koide ‘472, Vanasse, and Liu. The skilled artisan would have been motivated to do so because Liu teaches that tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab and is engineered in such a way to minimize antibody-dependent phagocytosis. There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of these antibodies individually in the treatment of solid tumors, and because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
(3)
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-7, 9-18, 21-27, 29-30, 32, 37, 39-43, 45, and 48 of co-pending Application No. 18/250,165 (reference application) in view of Koide ‘472 (US 2019/0127472 A1; supra), Vanasse (WO 2021/123902 A1; supra), and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363; supra).
The ‘165 reference application claims a method of treating a solid tumor (ocular melanoma) by administering an anti-Galectin-9 antibody comprising identical heavy chain and light chain CDRs to those instantly claimed, at a dose of about 0.2 mg/kg to about 32 mg/kg, including about 6.3 mg/kg, or about 10 mg/kg, or about 16 mg/kg, once a week and by intravenous infusion (co-pending claims 1 and 11-16), pertinent to claims 1, 4-8, and 12-17. Co-pending claim 10 recites that the solid tumor is metastatic, relevant to claim 3. Co-pending claims 4-7 recite that the anti-Galectin-9 antibody is an IgG1 or IgG4 antibody, and comprises identical VH/VL amino acid sequences, heavy chain/light chain sequences, and modified IgG4 Fc sequences as those recited in claims 18-22. Co-pending claims 18 and 21-22 recite that the anti-Galectin-9 antibody is further intravenously administered with tislelizumab at a dose of about 200 mg once every three weeks or about 400 mg once every six weeks, relevant to claims 1 and 9-11.
Co-pending claims 30 and 32 recite that the subject has undergone one or more anti-cancer therapies and resistant to said therapy(-ies) and/or has an elevated level of Galectin-9 relative to a control value, relevant to claims 23 and 25-26. Co-pending claims 37 and 39 recite further monitoring occurrence of one or more adverse effects in the human subject and reducing the dose of the anti-Galectin-9 antibody and/or checkpoint inhibitor when an adverse effect is observed, relevant to claims 29-30.
While the ‘165 reference application does not expressly teach that (1) the one or more prior anti-cancer therapies comprises, e.g., immunotherapy, or (2) treating NSCLC or head and neck cancer, or (3) that the human patient has elevated serum or plasma Galectin-9 levels, or (4) the tislelizumab is administered at a dose of about 300 mg every four weeks, these deficiencies are remedied by Koide ‘472, Vanasse, and Liu as taught in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the method of treating solid tumors recited in the co-pending claims, which comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., at a dose of about 0.2 mg/kg to about 18 mg/kg) and tislelizumab (e.g., administered at a dose of about 300 mg every four weeks), based on the further teachings of Koide ‘472, Vanasse, and Liu. The skilled artisan would have been motivated to do so because Liu teaches that tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab and is engineered in such a way to minimize antibody-dependent phagocytosis and because the antibody can also treat NSCLC or head and neck cancers expressing galectin-9. There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of these antibodies individually in the treatment of solid tumors, and because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
(4)
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-13, 15-16, 19-20, 22, 24, 26, and 31-32 of co-pending Application No. 18,253,756 (reference application) in view of Koide ‘472 (US 2019/0127472 A1; supra), Vanasse (WO 2021/123902 A1; supra), and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363; supra).
The ‘756 reference application recites a method of treating a solid tumor (e.g., metastatic tumor) by administering an anti-Galectin-9 antibody comprising identical heavy chain and light chain CDRs to those instantly claimed, at a dose of about 1 mg/kg to about 32 mg/kg, by intravenous infusion (co-pending claims 1, 3, 5-6), pertinent to claims 1, 3-5, 8, and 12-15. Co-pending claims 6, 8-10, and 12 recite that the method further comprise intravenously administering tislelizumab, further relevant to claim 1. Co-pending claims 13, 15-16, and 19-20 recite that the anti-Galectin-9 antibody is an IgG1 or IgG4 antibody, and comprises identical VH/VL amino acid sequences, heavy chain/light chain sequences, and modified IgG4 Fc sequences as those recited in claims 18-22.
Co-pending claims 22 and 24 recite that the subject has undergone one or more anti-cancer therapies (e.g., immunotherapy) and is resistant to said therapy(-ies), relevant to claims 23-25. Co-pending claim 26 recites that the human patient has an elevated level of Galectin-9 relative to a control value in serum or plasma, relevant to claims 17 and 26-27, or has cancer cells or immune cells expressing Galectin-9, relevant to claims 17 and 28. Co-pending claims 31-32 recite further monitoring occurrence of one or more adverse effects in the human subject and reducing the dose of the anti-Galectin-9 antibody and/or checkpoint inhibitor when an adverse effect is observed, relevant to claims 29-30.
While the ‘756 application does not expressly teach that (1) the solid tumor is, e.g., NSCLC or head and neck cancer; or (2) the anti-Galectin-9 antibody is administered once per week; or (3) tislelizumab is administered at a dose of about 300 mg every four weeks, these deficiencies are remedied by Koide ‘472, Vanasse, and Liu as taught in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the method of treating solid tumors (e.g., NSCLC or head and neck cancer) recited in the co-pending claims, which comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., at a dose of about 0.2 mg/kg to about 18 mg/kg) and tislelizumab (e.g., administered at a dose of about 300 mg every four weeks), based on the further teachings of Koide ‘472, Vanasse, and Liu. The skilled artisan would have been motivated to do so because Liu teaches that tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab and is engineered in such a way to minimize antibody-dependent phagocytosis. There would have been a reasonable expectation of success because those of ordinary skill in the art would have recognized the suitability of each of these antibodies individually in the treatment of solid tumors, and because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
(5)
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6-8, 11-14, 16, 18, 20, 22-23, 30-31, 33, and 38 of co-pending Application No. 18/556,387 (reference application) in view of Koide ‘472 (US 2019/0127472 A1; supra), Vanasse (WO 2021/123902 A1; supra), and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363; supra).
The ‘387 reference application claims methods for treating solid tumors (e.g., metastatic solid tumors; head and neck cancer) by administering an anti-Galectin-9 antibody comprising identical heavy chain and light chain CDRs to those instantly claimed, at a dose of about 0.2 mg/kg to about 32 mg/kg once per week, by intravenous infusion (co-pending claims 1, 3, 6-8, 11-13), pertinent to claims 1-8 and 12-15. Co-pending claims 16, 18, and 20 recite that the anti-Galectin-9 antibody is an IgG1 or IgG4 antibody, and comprises identical VH/VL amino acid sequences, heavy chain/light chain sequences, and modified IgG4 Fc sequences as those recited in claims 18-22. Co-pending claims 22-23 recite that the method further comprises administering tislelizumab, further relevant to claim 1.
Co-pending claims 30-31 recite that the subject has undergone one or more anti-cancer therapies (e.g., immunotherapy) and is resistant to said therapy(-ies), relevant to claims 23-25. Co-pending claim 33 recites that the human patient has an elevated level of Galectin-9 relative to a control value in serum or plasma, relevant to claims 17 and 26-27, or has cancer cells or immune cells expressing Galectin-9, relevant to claims 17 and 28. Co-pending claim 38 recites further monitoring occurrence of one or more adverse effects in the human subject and reducing the dose of the anti-Galectin-9 antibody and/or checkpoint inhibitor when an adverse effect is observed, relevant to claims 29-30.
While the ‘387 application does not expressly teach that tislelizumab is administered at a dose of about 300 mg every four weeks, these deficiencies are remedied by Koide ‘472, Vanasse, and Liu as taught in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the method of treating solid tumors recited in the co-pending claims, which comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., at a dose of about 0.2 mg/kg to about 18 mg/kg) and tislelizumab (e.g., administered at a dose of about 300 mg every four weeks), as determined through the course of routine optimization. The skilled artisan would have been motivated to do so because Koide ‘472 teaches that the combination of an anti-Galectin-9 and anti-PD-1 antibody have utility in the treatment of various solid tumors. There would have been a reasonable expectation of success because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
(6)
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 10-12, 16-19, 22, 30, 32-33, and 39-40 of co-pending Application No. 19/323,645 (reference application) in view of Koide ‘472 (US 2019/0127472 A1; supra), Vanasse (WO 2021/123902 A1; supra), and Liu (Expert Opinion on Investigational Drugs (2020) 29(12): 1355-1363; supra).
The ‘645 reference application claims a method for treating solid tumors (e.g., metastatic solid tumors) by administering an anti-Galectin-9 antibody comprising identical heavy chain and light chain CDRs to those instantly claimed, at a dose of about 1 mg/kg to about 32 mg/kg by intravenous infusion (co-pending claims 1, 3-4, 6-8), pertinent to claims 1, 3-5, 7-8, and 12-15. Co-pending claims 10-12 recite that the method further comprises administering tislelizumab, further relevant to claim 1. Co-pending claims 16-19 and 22 recite that the anti-Galectin-9 antibody is an IgG1 or IgG4 antibody, and comprises identical VH/VL amino acid sequences, heavy chain/light chain sequences, and modified IgG4 Fc sequences as those recited in claims 18-22. Co-pending claims 30 and 32 recite that the subject has undergone one or more anti-cancer therapies (e.g., immunotherapy) and is resistant to said therapy(-ies), relevant to claims 23-25. Co-pending claim 33 recites that the human patient has an elevated level of Galectin-9 relative to a control value, relevant to claims 17 and 26. Co-pending claims 39-40 recite further monitoring occurrence of one or more adverse effects in the human subject and reducing the dose of the anti-Galectin-9 antibody and/or checkpoint inhibitor when an adverse effect is observed, relevant to claims 29-30.
While the ‘645 application does not expressly teach that (1) the solid tumor to be treated is, e.g., NSCLC or head and neck cancer, or (2) tislelizumab is administered at a dose of about 300 mg every four weeks, or (3) the treated subject has elevated Galectin-9 in plasma or serum, or (4) the treated subject has cancer cells and/or immune cells expressing Galectin-9, these deficiencies are remedied by Koide ‘472, Vanasse, and Liu as taught in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the method of treating solid tumors recited in the co-pending claims, which comprises administering to a subject in need thereof the combination of an anti-Galectin-9 antibody (e.g., at a dose of about 0.2 mg/kg to about 18 mg/kg) and tislelizumab (e.g., administered at a dose of about 300 mg every four weeks), as determined through the course of routine optimization. The skilled artisan would have been motivated to do so because Koide ‘472 teaches that the combination of an anti-Galectin-9 and anti-PD-1 antibody have utility in the treatment of various solid tumors. There would have been a reasonable expectation of success because “‘It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.’ In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. See MPEP § 2144.06 (I).
Conclusion
No claims are allowed.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
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