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 .
The following are new grounds of rejection, necessitated by Applicant’s amendments:
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 6-37 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.
In claim 1, it is unclear if taxane is one of the “systemic therapies”.
The term “SG” should be written out, i.e., sacituzumab govitecan, in claims 31-7.
The rejection under section 103 is maintained and its application to any new claims was necessitated by Applicant’s amendments.
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.
Claims 1, 2, 6-37 are rejected under 35 U.S.C. 103 as being unpatentable over https://en.wikipedia.org/wiki/Sacituzumab_govitecan, 23 April 2020. Retrieved 7 October 2025 (TRODELVY); or
Prescribing Information, TRODELVY (sacituzumab govitecan-hziy) for injection, for intravenous use; downloaded from: https://web.archive.org/web/20200507011644/https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf 2020. Retrieved 7 October 2025 (Prescribing Information, TRODELVY); in view of:
Ponde et al., Curr. Treat. Options in Oncol. (2019) 20: 37 (Ponde); and
Bardia et al., The New England Journal of Medicine, 380 (8), 741-751 (Bardia); and
Wen et al., Ann Transl Med 2022;10(24):1403 (Wen); and
Fleming et al., J Adv Pract Oncol. 2021 Sep 1;12(7):747–752, newly cited (Fleming).
“TRODELVY” and “Prescribing Information, TRODELVY” both demonstrate that Sacituzumab govitecan-hziy (TRODELVY) is approved for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.
Efficacy was demonstrated in IMMU-132-01 (NCT 01631552), a multicenter, single-arm, trial enrolling 108 patients with metastatic triple negative breast cancer (mTNBC) who received at least two prior treatments for metastatic disease. Patients received sacituzumab govitecan-hziy 10 mg/kg intravenously on days 1 and 8 every 21days. Tumor imaging was obtained every 8 weeks, and patients were treated until disease progression or intolerance to therapy.
The primary efficacy outcome measures were investigator assessed overall response rate (ORR) using RECIST 1.1 and response duration. The ORR was 33.3% (95% CI: 24.6, 43.1). The median response duration was 7.7 months (95% CI: 4.9, 10.8).
The most common adverse reactions (≥25% of patients) were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. Sacituzumab govitecan-hziy can also cause severe neutropenia and diarrhea.
The recommended sacituzumab govitecan-hziy dose is 10 mg/kg administered by intravenous infusion administered on days 1 and 8 every 21 days until disease progression or unacceptable toxicity., see TRODELVY.
See also, Prescribing Information, TRODELVY:
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The primary references may fail to teach administration of Sacituzumab govitecan (SC) after previous endocrine or chemotherapies. However, the prior art demonstrates that antibody-drug conjugates (ADC’s), such as SC, are options after previously-failed therapies such as chemotherapies and endocrine-based therapies. See Ponde: (“breakthroughs are occurring in the orphan triple-negative breast cancer subtype with agents targeting surface proteins. The recent results of Sacituzumab govitecan suggest substantial activity in heavily pre-treated patients and underscore the enduring relevance of antibody drug conjugates as a path towards better outcomes [See Abstract].”).
Based on its potential, this agent received breakthrough designation from the FDA and the phase III ASCENT (NCT02574455) trial was opened, planning to randomize 328 patients with advanced TNBC who have failed at least two previous lines of therapy (including at least on containing a taxane) between sacituzumab govitecan and physician’s choice of therapy (including eribulin), see page 14.
In coming years, though some ADCs may come into clinical use as monotherapy, combinations of ADCs, particularly with immunotherapy, are likely to further improve outcomes, see Conclusion.
Antibody-drug conjugates are an elegant approach to cancer treatment that couples the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents, permitting, at least in theory, increased activity and reduced toxicity, not offered by conventional chemotherapies or endocrine therapy, see Abstract.
See also pages 37 and 38:
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Bardia teaches that SC is a viable option for patients with metastatic triple-negative breast cancer with poor outcomes:
The long-term efficacy of the various treatment options for patients with metastatic triple-negative breast cancer (serial application of single agents) is limited.12-14,16 Poor outcomes seen in patients with metastatic triple-negative breast cancer, as compared with other breast cancer subtypes, are partly explained by the lack of actionable driver mutations or established molecular targets, there-by leaving sequential single-agent chemotherapy as the main treatment approach.7,10 Sacituzumab govitecan-hziy is an antibody–drug conjugate with Trop-2 as the target of recognition; it can deliver cytotoxic chemotherapy to tumors, including ad-jacent cancer cells, in concentrations that are higher than those with standard chemotherapy and may reduce toxic effects in normal tissues that do not express the target.24 High expression of Trop-2 in triple-negative breast cancer and its association with a poor prognosis suggest that it is a rational therapeutic target in this patient population, see conclusion.
Wen teaches that SC TROP2-targeting offers an alternative to conventional therapies:
The availability of TROP2-targeting ADCs makes TROP2 an accessible and promising therapeutic target for advanced metastatic cancers. The present review describes the important role of TROP2 in tumorigenesis and its potential applications as a promising biomarker and therapeutic target that is capable of reversing resistance, see conclusion.
In this way, those of ordinary skill could have applied the SC in the manner required and in a reasonably predictable fashion for the purposes of providing a cancer therapy after previously-failed therapies. As outlined above, the primary references teach SC is approved for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. The secondary references are added for the proposition that SC is applicable as breast cancer therapy after other failed chemotherapies and endocrine-based therapies. Specifically, the secondary references teach that the particular known technique of using ADC’s, such as SC, as a secondary option for breast cancer therapy, was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique after failed chemotherapies and endocrine-based therapy would have yielded predictable results. Accordingly, using a SC for the purposes of providing ADC-based therapy after chemo- and endocrine-based therapies would have been prima facie obvious.
The claims may fail to teach effective amounts of SC. However, the amount of SC in the disclosed composition is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
The claims have been amended to recite that:
the breast cancer is unresectable locally advanced, or metastatic, HR+/HER2- (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer in a population of human subjects that is statistically significantly superior to a treatment of physician's choice (TPC),
wherein the population of human subjects previously received an endocrine-based therapy, a CDK4/CDK6 inhibitor, and two to four additional systemic therapies in a metastatic setting, wherein the human subjects previously received a taxane, and
wherein the treatment of physician's choice is selected from the group consisting of eribulin, capecitabine, gemcitabine, and vinorelbine.
However, those of ordinary skill would have reason to administer Sacituzumab govitecan (SG) in these situations since, as outlined above. Also:
SG is approved for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease, see above; and
SG targets TROP-2, which is a different target than those modes of action recited in the claims; and
Patients with historically HER2-negative unresectable/metastatic BC may benefit from HER2-low-directed treatments, such as antibody-drug conjugates, e.g., SG.
HER2-low status has become clinically actionable with the availability of these conjugates as a treatment option. Specifically, SG is an FDA-approved antibody-drug conjugate (ADC) for pre-treated metastatic HER2-low breast cancer, see Fleming (“Triple-negative breast cancer lacks expression of estrogen receptors, progesterone receptors, and HER2 receptors, and is associated with poor patient outcome.”).
Therefore, administration of SG for patients with metastatic triple-negative breast cancer who received the recited prior therapies would have been obvious.
In the absence of unexpected results, the dosing therapies recited in the claims are results-effective variable subject to routine optimization.
The rejected claims also recite survival rates that would have been as aspect of SG administration, and therefore, prima facie obvious.
The double patenting rejection remains outstanding:
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, 2, 6-37 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-69 of U.S. Application No. 18/671,393. Although the claims at issue are not identical, they are not patentably distinct from each other.
Specifically, the conflicting claims anticipate the methods covered by the rejected claims.
Alternatively, the difference between the methods covered by the conflicting claims and the methods covered by the rejected claims is that the conflicting claims may not recite the instant methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the elements of the instant methods with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
The conflicting claims may fail to recite the instant effective amounts of SC. However, the amount of SC in the disclosed composition is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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