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 .
Status of the Claims
Claims 1-38 were originally filed December 17, 2022.
The amendment received May 15, 2023 amended claims 1, 12, 14, 22, 23, 27, 29, 31, and 34-36; cancelled claims 4-6, 9-11, 13, 15, 16, 19-21, 26, 28, 30, 32, 33, 37, and 38; and added new claim 39.
The amendment received November 19, 2024 amended claim 1.
The amendment received December 5, 2025 changed the status identifiers only.
The amendment received May 4, 2026 amended claims 1, 3, 12, 14, 17, 18, 22-25, 27, 29, 31, 34, and 39 and canceled claims 7, 8, 35, and 36. Please note: claims 14, 23-25, 27, and 29 have improper status identifiers (i.e. “(Currently amended)” instead of “(Currently amended, Withdrawn)”).
Claims 1-3, 12, 14, 17, 18, 22-25, 27, 29, 31, 34, and 39 are currently pending.
Claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 are currently under consideration.
Election/Restrictions
Applicants elected, without traverse, a patient diagnosed with glioblastoma, primary glioblastoma, ST101 (SEQ ID NO: 2), IV infusion for a total of 30-360 minutes, administered weekly for at last three weeks, an antihistamine administered within about 48 hours of SEQ ID NO: 2/ST101 in the reply filed on December 5, 2025. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Please note: species requirements are not “optional”. Therefore, the “optional” election was not considered.
Claims 2, 14, 23-25, 27, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Priority
The present application is a 371 (National Stage) of PCT/US2021/038264 filed June 21, 2021 which claims the benefit of 63/172,560 filed April 8, 2021; 63/041,991 filed June 21, 2020; 63/041,990 filed June 21, 2020; 63/041,989 filed June 21, 2020; 63/041,988 filed June 21, 2020; and 63/041,986 filed June 21, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 4, 2026 is being considered by the examiner.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Objections
The objection to the disclosure regarding the first line of the specification should be updated to include PCT/US2021/038264 filed June 21, 2021 is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 8 regarding the arbitrary name of “ST101” should be replaced with “SEQ ID NO: 2” (see paragraph 2 of the originally filed specification) is withdrawn in view of the cancellation of the claim in the amendment received May 4, 2026.
The objection to claim 12 regarding all method steps should be recited as active, positive steps (i.e. administered should read administering) is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 17 regarding all method steps should be recited as active, positive steps (i.e. administered should read administering) is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 18 regarding all method steps should be recited as active, positive steps (i.e. administered should read administering) is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 22 regarding the arbitrary name of “ST101” should be replaced with “SEQ ID NO: 2” (see paragraph 2 of the originally filed specification) is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 22 regarding acronyms should be defined with the first recitation in the claim is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 31 regarding all method steps should be recited as active, positive steps (i.e. administered should read administering) is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 34 regarding all method steps should be recited as active, positive steps (i.e. administered should read administering) is withdrawn in view of the amendment received May 4, 2026.
The objection to claim 35 regarding the arbitrary name of “ST101” should be replaced with “SEQ ID NO: 2” (see paragraph 2 of the originally filed specification) is withdrawn in view of the cancellation of the claim in the amendment received May 4, 2026.
The objection to claim 36 regarding the arbitrary name of “ST101” should be replaced with “SEQ ID NO: 2” (see paragraph 2 of the originally filed specification) is withdrawn in view of the cancellation of the claim in the amendment received May 4, 2026.
The objection to claim 39 regarding all method steps should be recited as active, positive steps (i.e. administered should read administering) is withdrawn in view of the amendment received May 4, 2026.
Withdrawn Rejections
The rejection of claim 1 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 (i.e. lack of antecedent basis) is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 3 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 (i.e. lack of antecedent basis) is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 7 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 is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 8 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 is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 18 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 (i.e. lack of antecedent basis) is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 22 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 is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 35 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 is withdrawn in view of the amendment received May 4, 2026 which canceled the claim.
The rejection of claim 36 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 is withdrawn in view of the amendment received May 4, 2026 which canceled the claim.
The rejection of claim 39 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 (i.e. lack of antecedent basis) is withdrawn in view of the amendment received May 4, 2026.
The rejection of claim 7 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of the amendment received May 4, 2026 which canceled the claim.
The rejection of claim 35 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of the amendment received May 4, 2026 which canceled the claim.
The rejection of claim 36 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of the amendment received May 4, 2026 which canceled the claim.
The rejection of claims 22, 31, 34-36, and 39 under 35 U.S.C. 103 as being unpatentable over Greene et al. U.S. Patent Application Publication 2016/0046686 published February 18, 2016; Su et al., 2018, Effect of Retro-Inverso Isomer of Bradykinin on Size-Dependent Penetration of Blood-Brain Tumor Barrier, Small, 14: 1702331 (9 pages); and Le Joncur et al., May 8, 2019 (online), Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization, EMBO Molecular Medicine, 11: e9034 (21 pages) is withdrawn in view of the amendment received May 4, 2026.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any claim requiring a specific percent identity, necessarily requires at least the recited percent identity.
Therefore, present independent claims 1 and 22 and all dependent claims require 100% identity to present SEQ ID NO: 2.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
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.
Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 22 recites the limitation "the patient" in line 4. There is insufficient antecedent basis for this limitation in the claim. Utilization of “the human patient” is suggested.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(b) as being indefinite (i.e. lack of antecedent basis) for claim 22 were considered but are not persuasive for the following reasons.
Applicants contend that the amendment received May 4, 2026 negates the rejection.
Applicants’ arguments are not convincing since the amendment received May 4, 2026 only amended one recitation which lacked antecedent basis when two recitations that lacked antecedent basis were present. See line 4.
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.
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, 12, 17, 18, 22, 31, 34, and 39 are rejected under 35 U.S.C. 103 as being obvious over Kappel et al. U.S. Patent Application Publication 2019/0201483 published July 4, 2019 (effective filing date of January 3, 2018); Greene et al. U.S. Patent Application Publication 2016/0046686 published February 18, 2016; and Le Joncur et al., May 8, 2019 (online), Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization, EMBO Molecular Medicine, 11: e9034 (21 pages).
The applied reference (U.S. Patent Application Publication 2019/0201483) has a common common assignee (Sapience Therapeutic, Inc.) and common inventors (Barry Kappel, Gene Merutka, and Jimmy Rotolo) 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).
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.
For present claims 1, 3, 12, 17, 18, 22, 31, 34, and 39, Kappel et al. teach methods of treating human patients with glioblastoma via administering a D amino acid retro inverso ATF5 bZIP domain/leucine zipper domain (VAEAREELERLEARLGQARGEL; SEQ ID NO: 65; residues 1-22 of present SEQ ID NO: 2/ST101) alone or in combination as a fusion protein with a CPP including modified penetratin (RQLKLWFQNRRMKWKK; SEQ ID NO: 26 wherein leucine is a conservative amino acid substitution from isoleucine of unmodified penetratin SEQ ID NO: 25; residues 23-38 of present SEQ ID NO: 2/ST101) and saline wherein the dosage was 20 mg/kg, 25 mg/kg, or 50 mg/kg and was administered twice a day, three times per week for three weeks, or twice daily for three weeks (please refer to the entire specification particularly the abstract; paragraphs 3-5, 8, 10-13, 17, 56-87, 110-115; Tables 1-3). Kappel et al. teach SEQ ID NO: 14 which is the same length and has 100% identity with present SEQ ID NO: 2/ST101.
However, Kappel et al. do not teach intravenous administration.
For present claims 1, 3, 12, 17, 18, 22, 31, 34, and 39, Greene et al. teach methods of treating glioblastoma in humans via administering ATF5 domains including leucine zippers and D amino acids fused to penetratin CPP RQIKIWFQNRRMKWKK wherein isoleucine is a conservative amino acid substitution for leucine (residues 23-38 of present SEQ ID NO: 2) and saline wherein the amount can be determined by the skilled artisan to be effective to treat glioblastoma and administered intravenously (please refer to the entire specification particularly the abstract; paragraphs 3-5, 6-10, 35-52, 59-62, 64, 65, 70-72, 76, 79, 83, 84). Greene et al. also teach coadministration with therapeutically effective agents including other anti-cancer agents (please refer to the entire specification particularly paragraph 85).
However, Kappel et al. do not teach antihistamines.
For present claims 17, 18, and 39, Le Joncour et al. teach methods of treating glioblastomas with antihistamines (please refer to the entire reference particularly the abstract; Introduction; Clemastine evokes glioma cell death; Discussion).
Generally, differences in concentration, temperature, or timing will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration, temperature, or timing 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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) and Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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."). See also In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because a particular known technique (intravenous administration, dosage, timing of administration, coadministration of anticancer therapeutics) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co v. Teleflex Inc., 82 USPQ2d1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Kappel et al.; Greene et al.; and Le Joncur et al. for claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 were considered but are not persuasive for the following reasons.
Applicants contend that Example 3 of Kappel et al. in an in vitro method and Example 4 teaches a mouse model with administration at doses of 25 mg/kg or 50 mg/kg. Applicants contend that Kappel et al. do not teach a method of treating a solid tumor in a human patient. Applicants state that Sun et al. (provided in the IDS received May 4, 2026) teaches unpredictability. Applicants refer to a poster provided in the IDS received May 4, 2026
Applicants’ arguments are not convincing since the teachings of Kappel et al.; Greene et al.; and Le Joncur et al. render the method of the instant claims prima facie obvious.
Kappel et al. teach human subjects and human patients (see paragraph 57).
Kappel et al. teach concentrations of 10, 20, 30, and 40 mM (see Figures 2-5, 6A, 6B, 6D, 6E, 7B); 10, 20, 40, and 80 mM (see Figure 6C); and additional concentrations (see Figures 7A, 7C, 7D, 7E). Kappell et al. also teach 5 mM (see Figures 8A, 8B); 5, 20, and 40 mM (see Figures 8C); and 20 mM (see Figure 8D). Kappell et al. teach EC50 values of 1.4, 4.8, 17.7, 19, 21.8, 29.6, 52.9, and 98.2 mM (see paragraph 23).
Kappell et al. teach 20 mg/kg, 25 mg/kg, and 50 mg/kg (see paragraphs 26-30; Example 4).
Greene et al. teach that an amount that is effective to treat the tumor and/or neoplastic cell in a subject to whom the pharmaceutical composition is administered. That amount may be readily determined by the skilled artisan. See paragraph 84.
Greene et al. teach 1 mg/kg (see paragraphs 98, 111).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." See In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
A prior art reference provides an enabling disclosure and thus anticipates or renders obvious a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation or obviousness." See Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006) and Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326, 75 USPQ2d 1297, 1302 (Fed. Cir. 2005)).
Conclusive proof of efficacy is not required to show a reasonable expectation of success. See OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"). See Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness.". See Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); and Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
Regarding Sun et al., the reference provides several different strategies to increase clinical drug development including choosing the best lead drug for clinical efficacy, minimal toxicity, and optimal drug-like properties.
In addition, evidence should be provided via a declaration (see MPEP § 716) or as an Exhibit (see 41.154, 42.63) and not in an IDS. Moreover, the poster is illegible in several areas.
Regarding Figure 8, PR stands for “partial response” and SD stands for “stable disease” (see paragraph 108; Table 1). Only certain cancers and certain doses provided a partial response or stable disease (i.e. 0.5 mg/kg for signet ring adenocarcinoma; 2 mg/kg for small bowel adenocarcinoma and abdominal sarcoma; and 4 mg/kg ). Therefore, any claimed unexpected results are not commensurate in scope with the present claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,525,100 in view of Greene et al. U.S. Patent Application Publication 2016/0046686 published February 18, 2016 and Le Joncur et al., May 8, 2019 (online), Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization, EMBO Molecular Medicine, 11: e9034 (21 pages).
U.S. Patent No. 10,525,100 claims methods of treating neoplastic cells with SEQ ID NO: 65 (present SEQ ID NO: 1; residues 1-22 of present SEQ ID NO: 2)
Greene et al. teach methods of treating glioblastoma in humans via administering ATF5 domains including leucine zippers (i.e. variants of ST101) and D amino acids fused to penetratin CPP RQIKIWFQNRRMKWKK wherein isoleucine is a conservative amino acid substitution for leucine (residues 23-38 of present SEQ ID NO: 2) and saline wherein the amount can be determined by the skilled artisan to be effective to treat glioblastoma and administered intravenously (please refer to the entire specification particularly the abstract; paragraphs 3-5, 6-10, 35-52, 59-62, 64, 65, 70-72, 76, 79, 83, 84). Greene et al. also teach coadministration with therapeutically effective agents including other anti-cancer agents (please refer to the entire specification particularly paragraph 85).
Le Joncour et al. teach methods of treating glioblastomas with antihistamines (please refer to the entire reference particularly the abstract; Introduction; Clemastine evokes glioma cell death; Discussion).
Generally, differences in concentration, temperature, or timing will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration, temperature, or timing 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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) and Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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."). See also In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because a particular known technique (intravenous administration to a human with glioblastoma, dosage, timing of administration, coadministration of anticancer therapeutics) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co v. Teleflex Inc., 82 USPQ2d1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 10,525,100 in view of Greene et al. and Le Joncur et al. for claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 were considered but are not persuasive for the following reasons.
Applicants contend that U.S. Patent No. 10,525,100 does not teach the exact method of the present claims.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 10,525,100 in view of Greene et al. and Le Joncur et al. renders obvious the method of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
U.S. Patent 10,525,100 claims a method of promoting cytotoxicity in a neoplastic cell, the method comprising contacting the neoplastic cell with the ATF5 peptide according to claim 1 (i.e. VAEAREELERLEARLGQARGEL – SEQ ID NO: 65 residues 1-22 of present SEQ ID NO: 2).
U.S. Patent 10,525,100 claims a method of inhibiting proliferation of a promoting neoplastic cell, the method comprising contacting the neoplastic cell with the ATF5 peptide according to claim 1 (i.e. VAEAREELERLEARLGQARGEL – SEQ ID NO: 65 residues 1-22 of present SEQ ID NO: 2).
Greene et al. and Le Joncur et al. provide the additional components of the presently claimed method (see above).
Greene et al. teach that an amount that is effective to treat the tumor and/or neoplastic cell in a subject to whom the pharmaceutical composition is administered. That amount may be readily determined by the skilled artisan. See paragraph 84.
Greene et al. teach 1 mg/kg (see paragraphs 98, 111).
Claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/985,452 in view of Greene et al. U.S. Patent Application Publication 2016/0046686 published February 18, 2016 and Le Joncur et al., May 8, 2019 (online), Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization, EMBO Molecular Medicine, 11: e9034 (21 pages).
Copending Application No. 18/985,452 claims methods of treating neoplastic cells with retroinverso and variants of SEQ ID NO: 53 which result in present SEQ ID NO: 1 (i.e. residues 1-22 of present SEQ ID NO: 2) and CPP of residues 23-38 of present SEQ ID NO: 2/ST101.
Greene et al. teach methods of treating glioblastoma in humans via administering ATF5 domains including leucine zippers (i.e. variants of ST101) and D amino acids fused to penetratin CPP RQIKIWFQNRRMKWKK wherein isoleucine is a conservative amino acid substitution for leucine (residues 23-38 of present SEQ ID NO: 2) and saline wherein the amount can be determined by the skilled artisan to be effective to treat glioblastoma and administered intravenously (please refer to the entire specification particularly the abstract; paragraphs 3-5, 6-10, 35-52, 59-62, 64, 65, 70-72, 76, 79, 83, 84). Greene et al. also teach coadministration with therapeutically effective agents including other anti-cancer agents (please refer to the entire specification particularly paragraph 85).
Le Joncour et al. teach methods of treating glioblastomas with antihistamines (please refer to the entire reference particularly the abstract; Introduction; Clemastine evokes glioma cell death; Discussion).
Generally, differences in concentration, temperature, or timing will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration, temperature, or timing 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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) and Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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."). See also In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because a particular known technique (intravenous administration to a human with glioblastoma, dosage, timing of administration, coadministration of anticancer therapeutics) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co v. Teleflex Inc., 82 USPQ2d1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 18/985,452 in view of Greene et al. and Le Joncur et al. for claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 were considered but are not persuasive for the following reasons.
Applicants contend that copending Application No. 18/985,452 only claims L-amino acids.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 18/985,452 in view of Greene et al. and Le Joncur et al. renders obvious the method of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Copending Application No. 18/985,452 claims D-amino acids in a reversed amino acid sequence (see claim 6).
Copending Application No. 18/985,452 claims a method of promoting cytotoxicity in a neoplastic cell, the method comprising contacting the neoplastic cell with the ATF5 peptide according to claim 1 (i.e. VAEAREELERLEARLGQARGEL – SEQ ID NO: 61 residues 1-22 of present SEQ ID NO: 2).
Copending Application No. 18/985,452 claims a method of inhibiting proliferation of a neoplastic cell, the method comprising contacting the neoplastic cell with the ATF5 peptide according to claim 1 (i.e. VAEAREELERLEARLGQARGEL – SEQ ID NO: 61 residues 1-22 of present SEQ ID NO: 2).
Greene et al. and Le Joncur et al. provide the additional components of the presently claimed method (see above).
Greene et al. teach that an amount that is effective to treat the tumor and/or neoplastic cell in a subject to whom the pharmaceutical composition is administered. That amount may be readily determined by the skilled artisan. See paragraph 84.
Greene et al. teach 1 mg/kg (see paragraphs 98, 111).
Claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 5, 13, 15, 17, 22-28, and 32 of copending Application No. 19/118,719 in view of Greene et al. U.S. Patent Application Publication 2016/0046686 published February 18, 2016 and Le Joncur et al., May 8, 2019 (online), Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization, EMBO Molecular Medicine, 11: e9034 (21 pages).
Copending Application No. 19/118,719 claims a method of inhibiting growth of a solid tumor in a subject via administering with SEQ ID NO: 2 (100% identity and the same length as present SEQ ID NO: 2) at 500 mg wherein the solid tumor is a melanoma, carcinoma, sarcoma, LA/MBC, GBM, or CRPC and administration is intravenously.
Greene et al. teach methods of treating glioblastoma in humans via administering ATF5 domains including leucine zippers (i.e. variants of ST101) and D amino acids fused to penetratin CPP RQIKIWFQNRRMKWKK wherein isoleucine is a conservative amino acid substitution for leucine (residues 23-38 of present SEQ ID NO: 2) and saline wherein the amount can be determined by the skilled artisan to be effective to treat glioblastoma and administered intravenously (please refer to the entire specification particularly the abstract; paragraphs 3-5, 6-10, 35-52, 59-62, 64, 65, 70-72, 76, 79, 83, 84). Greene et al. also teach coadministration with therapeutically effective agents including other anti-cancer agents (please refer to the entire specification particularly paragraph 85).
Le Joncour et al. teach methods of treating glioblastomas with antihistamines (please refer to the entire reference particularly the abstract; Introduction; Clemastine evokes glioma cell death; Discussion).
Generally, differences in concentration, temperature, or timing will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration, temperature, or timing 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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) and Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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."). See also In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because a particular known technique (intravenous administration to a human, dosage, timing of administration, coadministration of anticancer therapeutics) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co v. Teleflex Inc., 82 USPQ2d1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection.
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over copending Application No. 19/118,719 in view of Greene et al. and Le Joncur et al. for claims 1, 3, 12, 17, 18, 22, 31, 34, and 39 were considered but are not persuasive for the following reasons.
Applicants contend that since copending Application No. 19/118,719 has a later filing date than the present application, that the provisional rejection should be withdrawn.
Applicants’ arguments are not convincing since the claimed invention of copending Application No. 19/118,719 in view of Greene et al. and Le Joncur et al. renders obvious the method of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02). The present claims are not in condition for allowance, therefore, the provisional rejection is maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO 2019/136125
U.S. Patent Application Publication 2018/0237499
U.S. Patent 10,316,077
U.S. Patent 11,878,047
U.S. Patent 12,208,131
Ran et al., 2017, D-Retroenantiomer of Quorum-Sensing Peptide-Modified Polymeric Micelles for Brain Tumor-Targeted Drug Delivery, ACS Appl Mater Interfaces, 9: 25672-25682.
Ren et al., 2018, A D-Peptide Ligand of Integrins for Simultaneously Targeting Angiogenic Blood Vasculature and Glioma Cells, Mol Pharmaceuticals, 15: 592-601.
Ying et al., 2016, Stabilized Heptapeptide A7R for Enhanced Multifunctional Liposome-Based Tumor-Targeting Drug Delivery, ACS Appl Mater Interfaces, 8: 13232-13241.
Wang et al., 2014, Retro-Inverso CendR Peptide-Mediated Polyethyleneimine for Intracranial Glioblastoma-Targeting Gene Therapy, Bioconjugate Chem, 25: 414-423.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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