DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 4, 5, 8-14, 16-22, 24, 26-31, 33, 35 and 36 are pending.
35 USC § 112(a) rejections withdrawn
The rejection of claims 1, 4, 5, 8-14, 17, 19-22, 24, 26-31 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter are withdrawn in view of Applicant’s amendments to claim 1.
Double Patenting rejections maintained
The rejections of claims 1, 4, 5, 8-14, 16-22, 24, 26-31, 33, 35 and 36 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 Delhem et al (US 2017/0283499, published October 5, 2017) and Lewis et al (US 2021/0009697, published January 14, 2021, filing date September 12, 2018) are maintained.
The claims are drawn to a method for treating a solid tumor, comprising administering to a subject in need thereof an effective amount of an antibody that binds human galectin-9 (anti-Gal9 antibody), and (b) an effective amount of one or more chemotherapeutics, wherein the anti-Gal9 antibody has the same heavy chain complementarity determining regions (CDRs) and the same light chain CDRs as antibody G9.2-17 and the one or more chemotherapeutics comprise gemcitabine, paclitaxel, or a combination thereof, wherein the anti-Galectin-9 antibody comprises a light chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 1, a light chain complementarity determining region 2 (CDR2) set forth as SEQ ID NO: 2, and a light chain complementarity determining region 3 (CDR3) set forth as SEQ ID NO: 3 and/or comprises a heavy chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 4, a heavy chain complementarity determining region 2 (CDR2) set
forth as SEQ ID NO: 5, and a heavy chain complementarity determining region 3 (CDR3) set forth as SEQ ID NO: 6.
The claims of U.S. Patent No. 10,450,374 are drawn to a method for inhibiting the activity of galectin-9 in a subject, the method comprising administering to the subject in need thereof an effective amount of a pharmaceutical composition comprising an isolated antibody, wherein the antibody comprises a heavy chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 361, a heavy chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 388,
and a heavy chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 406 and/or comprises a light chain complementarity determining region 1 (CDRl)which binds human galactin-9, set forth as SEQ ID NO: 328, a light chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 329, and a light chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 352, wherein the antibody comprises a VH set forth as SEQ ID NO: 55 and/or a VL set forth as SEQ ID NO: 54, wherein the subject is suspected of having, or is at risk for a solid tumor, including pancreatic cancer, wherein the method further comprises administering to the human subject an effective amount of a checkpoint inhibitor.
The antibody recited in the claims of U.S. Patent No. 10,450,374 is identical to the recited antibody of the present claims (see sequence comparison below.
The claims of U.S. Patent No. 10,450,374 do not specifically recite the chemotherapeutic agents, gemcitabine or paclitaxel.
However, Delhem disclose administering an anti-galactin antibody along with a chemotherapeutic agent (paragraphs 1, 141, 153).
Lewis disclose the administration of an anti-PD-1 antibody along with the chemotherapeutic agents gemcitabine and paclitaxel for the treatment of pancreatic cancer (paragraphs 7-19).
One of ordinary skill in the art would have been motivated to combine the antibody of U.S. Patent No. 10,450,374 with Delhem and Lewis’s treatment of pancreatic cancer with antibodies along with gemcitabine and paclitaxel because the claims of U.S. Patent No. 10,450,374, Delhem and Lewis all disclose treatments for pancreatic cancer, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
With regard to the dosage regimens of claims 8-11, 13, 14, 33 and 35 these are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The provisional rejections of claims 1, 4, 5, 8-14, 16-22, 24, 26-31, 33, 35 and 36 on the ground of nonstatutory double patenting as being unpatentable over claims 37-65 of copending Application No. 17/598,215 are maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Application No. 17/598,215 are drawn to a method of modulating immune response in a solid tumor of a subject, the method comprising administering to the subject in need thereof an effective amount of a pharmaceutical composition comprising an isolated antibody, which binds human galectin-9, wherein the antibody comprises a VH set forth as SEQ ID NO: 10 and a VL set forth as SEQ ID NO: 9, further comprises administering to the subject an effective amount of a checkpoint inhibitor and/or a chemotherapeutic agent, wherein the chemotherapeutic agent is gemcitabine and/or paclitaxel, wherein the solid tumor is pancreatic cancer. The antibody claimed in Application No. 17/598,215 is identical to the presently claimed antibody (see sequence comparisons below).
With regard to the dosage regimens of claims 8-11, 13, 14, 33 and 35 these are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The provisional rejections of claims 1, 4, 5, 8-14, 16-22, 24, 26-31, 33, 35 and 36 on the ground of nonstatutory double patenting as being unpatentable over claims 17-40 of copending Application No. 17/851,930 are maintained. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Application No. 17/851,930 are drawn to a method for inhibiting the activity of galectin-9 or treating a solid tumor in a subject, the method comprising administering to the subject, wherein the pharmaceutical composition comprises an antibody comprising a heavy chain comprising SEQ ID NO: 316 and a light chain comprising SEQ ID NO: 108, wherein the solid tumor is pancreatic cancer, further comprising subjecting the human patient to an immunotherapy, or a chemotherapy, wherein the chemotherapy comprises gemcitabine, paclitaxel, or a combination thereof.
The antibody claimed in Application No. 17/851,930 is identical to the presently claimed antibody (see sequence comparisons below).
With regard to the dosage regimens of claims 8-11, 13, 14, 33 and 35 these are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s argue that Delham provides a generic disclosure of combining an
anti-Gal9 antibody with chemotherapy but provides no teaching or suggestion for the
combination of gemcitabine and paclitaxel involved in the instant claims. Applicant argues that the combination of the claims of the '374 patent and Delham would not have arrived at the instant claims.
Applicant further argues that Lewis cannot cure this deficiency because this reference does not touch on anti-Gal9 antibodies in cancer therapy. Applicant argues that the claims of the obvious-type patent rejections focuses on anti-Gal9 antibody in
cancer therapy, there would have been no motivation to combine the claims of the '374 patent with Lewis to arrive at the instant claims with a reasonable expectation of success.
Applicant arguments have been considered but are not persuasive. In response to applicant's arguments against Delham and Lewis individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Delhem disclose administering an anti-galactin antibody along with a chemotherapeutic agent to treat pancreatic cancer (paragraphs 1, 141, 153).
Lewis disclose the administration of an anti-PD-1 antibody along with the chemotherapeutic agents gemcitabine and paclitaxel for the treatment of pancreatic cancer. U.S. Patent No. 10,450,374, copending Application No. 17/851,930 and copending Application No. 17/598,215 all disclose the treatment of pancreatic cancer with the claimed antibody. Thus, all the claim limitations are present in Delhem, Lewis, U.S. Patent No. 10,450,374, copending Application No. 17/851,930 and copending Application No. 17/598,215 and there is ample motivated to combine Delhem and Lewis with U.S. Patent No. 10,450,374, copending Application No. 17/851,930 and copending Application No. 17/598,215. The court has held that it is obvious to combine two compositions, in order to form a third composition, when each of the two compositions is taught by the prior art to be useful for the same purpose. (In re Kerkhoven, 626, F.2s 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. Thus, absent unexpected results it would have been obvious to combine Delhem and Lewis with U.S. Patent No. 10,450,374, copending Application No. 17/851,930 and copending Application No. 17/598,215.
In addition, Applicant argues that unexpected results reported in the instant application would be sufficient to rebut a prima facie finding of obviousness. Applicant argues that the instant application provides experimental data showing superior therapeutic effects arising from the claimed combined treatment in mouse models of pancreatic adenocarcinoma (PDAC) as an example of solid tumor. Applicant argues that Example 1 discloses the combined use of a mouse surrogate of anti-Gal9 antibody G9.2-l 7, gemcitabine and Abraxane® (nanoparticle albumin-bound Paclitaxel) in a mouse PDAC model. As shown in FIG. 1A and Tables 3-5 of the specification, the chemotherapy combination of gemcitabine and Abraxane® produced only a limited anti-tumor activity with a mean survival of 28 days (as compared with the 27 days for the control group) and the last mouse euthanized (survived) on day 41 (Hazard Ratio 0.624). The anti-galectin 9 antibody alone showed an improved mean survival at 32 days and the last mice for this group survived on day 55 (Hazard Ratio 0.348).
Applicant argues that the combination treatment of the anti-Gal9 antibody, gemcitabine, and Abraxane® showed better therapeutic effects, improving the mean survival date to 34 days and the last mice survived on day 66 (Hazard Ratio 0.336). Applicant argues that given the limited therapeutic effects achieved by the gemcitabine and paclitaxel combination, the superior anti-tumor effects achieved by the claimed combination therapy would be unexpected.
Applicant’s arguments have been considered but are not persuasive. Table 4 indicates that there was no significant difference between the group receiving the anti-Gal9 mAb and the group receiving the Gal9 mAb, gemcitabine and Abraxane. Furthermore, it appears as if there is no difference between the negative control group and the group receiving gemcitabine and Abraxane, a first line treatment for pancreatic cancer. It is not clear from Example 1 whether the results were unexpected.
Furthermore, Wiesenthal, (Human Tumor Assay Journal, on-line at (http://weisenthal.org/synergy1.htm, March 14, 2012) discusses the question of synergy between drug combinations and diseases.
Most "classic" drug combinations are only additive or are, at most, minimally synergistic. Examples of merely additive drug combinations are cisplatin/5FU, cisplatin/Taxol, and cisplatin/etoposide. However, some newer combinations show greater degrees of synergy, including cisplatin/topotecan, gemcitabine/platinum, and gemcitabine/alkylators. The profound synergy between gemcitabine/platinum in vitro has now been confirmed in the clinic in a number of settings. The similar degree of synergy between gemcitabine and alkylating agents suggest that these combinations should be explored in clinical settings in which alkylating agents are known to be important, particularly higher dose regimens with growth factor and/or stem cell support.
In particular, Weisenthal states that combination chemotherapy frequently, but not always, has produced greater degrees of clinical benefit than single agent therapy.” Wiesenthal further states that most “classic” drug combinations are only additive or are at most, minimally synergistic.
Applicants have not demonstrated that co-treatment with the Gal9 mAb, gemcitabine and Abraxane had synergistic effects in suppressing neoplastic cell proliferation. In addition, as previously disclosed, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.).
Furthermore, MPEP 716.02(d) states
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at “elevated temperatures” using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110C and 130C. The court affirmed the rejection of claims 1-7 and 9-10 because the term “elevated temperatures” encompassed temperatures as low as 60C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.).
The unexpected results involve the treatment of pancreatic cancer with specific therapeutic regimens of Gal9 mAb, gemcitabine and Abraxane. The present claims do not reflect the specific therapeutic regimens used in Example 1.
Summary
Claims 1, 4, 5, 8-14, 16-22, 24, 26-31, 33, 35 and 36 stand rejected
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/MARK HALVORSON/Primary Examiner, Art Unit 1646