DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/11/2025 has been entered.
Status of Application
The response filed 12/11/2025 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 1,3, 10-11, 16, 30 have been amended.
Claims 70-71 has been added.
Applicant had previously elected Group I in response to restriction requirement and elected the species of G-CSF drug to be pegfilgrastim, the elected species of the chemotherapy to be TAC (docetaxel, doxorubicin, cyclophosphamide) which was expanded to include docetaxel and the combination of docetaxel with cyclophosphamide, and the election of species for the cancer to be non-small cell lung cancer for the examination. Based on the elections/expansion, claims 40, 50, 52-55, 57-59, 62 are withdrawn from further consideration.
Claims 1, 3, 5, 10-11, 16-17, 19, 22, 30, 33, 40, 50, 52-55, 57-59, 62, 70-71 are pending.
Claims 1, 3, 5, 10-11, 16-17, 19, 22, 30, 33, 70-71 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
There is an approved terminal disclaimer for copending application 17/877198 and U.S. Pat. 11400086.
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
New grounds of rejection are set forth in the current office action as a result of amendment.
New Grounds of Rejection
Due to the amendment of the claims the new grounds of rejection are applied:
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly
pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 5, 10-11, 16-17, 19, 22, 30, 33, 70-71 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.
The claim is amended to recite “A method of treating a chemotherapy induced neutropenia, comprising co-administering plinabulin and one or more G-CSF drugs, wherein a first dose of plinabulin is administered within 24 hours after a first administration of a chemotherapeutic agent in a chemotherapy regimen; wherein the one or more G-CSF drugs are administered at least 24 hours after a last administration of a chemotherapeutic agent in the chemotherapy regimen, and are administered within 7 days after administration of a dose of plinabulin; and wherein plinabulin reduces one or more adverse effects associated with the G-CSF drug during treatment of the chemotherapy-induced neutropenia”.
This is confusing. The claim recites - a first dose of plinabulin is administered within 24 hours after a first administration of a chemotherapeutic agent in a chemotherapy regimen; wherein the one or more G-CSF drugs are administered at least 24 hours after a last administration of a chemotherapeutic agent in the chemotherapy regimen – but it is unclear what constitutes the chemotherapy regimen – is it the individual round of chemotherapy? It is the entire length of chemotherapy wherein the last dose is the last dose of chemotherapy for the patient? If it is the individual round of chemotherapy – the claim recites a first dose and a last dose wherein when there is one infusion of a chemotherapeutic such as docetaxel (as infusions are over time), is it both the first and last dose? Or is it for a more than one agent chemotherapy but then dependent claims like claim 3 and 30 which embrace one would be broader than the independent claim which is also indefinite and a 112 4th issue. It does not allow one to ascertain the metes and bounds of the claim as written. For purposes of examination, the claims are treated where the chemotherapy regimen is an individual round of chemotherapy (as most people receive multiple rounds of chemotherapy), and the first/last dose of chemotherapy may be the same (i.e. as an infusion/dose of docetaxel).
Claim 70 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.
The claim recites that the chemotherapy comprises TAC but does not recite what TAC is wherein it is unclear what the acronym stands for. For purposes of examination, the TAC chemotherapy is treated to mean docetaxel, doxorubicin, and cyclophosphamide.
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 1,3, 5, 10-11, 17, 19, 22, 30, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (U.S. Pat. Pub. 2016/0250209) in view of Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia).
Rejection:
Huang teaches treating cancer such as NSCLC (non-small cell lung cancer) and lowering the side effects of taxane compound such as decreasing the neutropenia rates (treating neutropenia from taxane/docetaxel) at all grades with the administration of the combination of plinabulin and a taxane compound like docetaxel (abstract, [3]).
Huang teaches Example 3 where patients with non-small cell lung cancer (NSCLC) were treated with docetaxel and then plinabulin (given 2 hours after docetaxel on day 1 at 20mg/m2 and 30mg/m2 doses, within 24 hours of chemo) and additional G-CSF (Pegfilgrastim (Neulasta), filgrastim (Neupogen)) on 21 day cycles - reducing the neutropenia side effect of the docetaxel in all grades especially >/= Grade 3 neutropenia (>Grade 3 neutropenia includes Grade 4 which the instant specification is <0.5x109/L, [223-227], Table 9, see full document specifically areas cited).
Huang is silent on when the G-CSF (pegfilgrastim or filgrastim) is given and how much is administered, Huang does teach the administration of the G-CSF like pegfilgrastim and filgrastim.
Crawford teaches that pegfilgrastim is given once-per-cycle and filgrastim is given daily for the management of chemotherapy-induced neutropenia. Crawford teaches that filgrastim is given daily on an average of 11 daily injections at 5ug/kg/d at 24 hours after treatment with chemotherapy. Crawford also teaches that a single dose of pegfilgrastim given 24 hours after chemotherapy reduce neutropenic complications and the doses used were 30ug/kg (about 2.1mg with 70kg/standard man), 100ug/kg (about 7mg), 300ug/kg (about 21mg) were useful, and that all weight groups were adequately protected with a single 6mg dose of pegfilgrastim (Abstract, Page 25 second column, Fig 2, Conclusion, see full document specifically areas cited).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to give the pegfilgrastim 24 hours after chemotherapy delivery at the known dosages like 6mg and 7mg, and filgrastim 24 hours after chemotherapy to start and daily afterward (an average for 11 days, is 2 or more doses from 24-48 hrs) as suggested by Crawford and produce the claimed invention; as it is implicit if not prima facie obvious to deliver the pegfilgrastim or filgrastim in its known useful regime and in its known useful dosage (i.e. pegfilgrastim 24 hours after chemotherapy i.e. day 2 which is within 7 days of plinabulin (and also within a day/24hours of plinabulin) that is administered on day 1, or daily like filgrastim 2 or more doses for an average for 11 days (i.e. one is at least 30 hours after the chemotherapeutic)) with a reasonable expectation of success. The effects of the administration of plinabulin with G-CSF such as the reduction of adverse effects associated with G-CSF are intrinsically present as it necessarily flow from the teaching of the applied prior art or the natural result of the combination of elements explicitly disclosed by the prior art, as the same drugs are given in the same time frame to the same cancer patients reducing the chemotherapeutic induced neutropenia.
Response to Arguments:
Applicant's arguments are centered on the assertions that the newly limitation that the G-CSF is administered within 7 day after the dose of plinabulin is not taught or suggested by the cited art, that one would not arrive at the claims for neutrophil support though routine optimization of the combination of plinabulin and G-CSF as it only applies when working toward a recognized goal with a defined set of predictable options and one did not know that plinabulin produces a neutrophil support effect within 24hours before Applicant’s work, cites Tonra et al. that plinabulin ameliorates chemotherapy induced neutropenia via a mechanism different from G-CSF which supports its use as an alternative or combinational approach, that the art does not appreciate that plinabulin can reduce adverse effects associated with G-CSF and improve the tolerability of full-dose G-CSF treatment, that the cited art does not recognize the timing and therapeutic interplay of plinabulin’s early neutrophil support with G-CSF’s delayed effect, and the assertion of unexpected results with the timing for the plinabulin and G-CSF would provide continuous protection across the neutrophil nadir which is not recognized by the cited art.
This is fully considered but not persuasive.
Contrary to Applicant’s assertion, the cited prior art does fall within the recited limitation as Huang teaches addressing the chemotherapy induced neutropenia in patients with non-small cell cancer with the administration of plinabulin 2 hours after docetaxel on day 1 at 20mg/m2 and 30mg/m2 doses (within 24 hours of chemo, day 1) and had administered additional G-CSF (Pegfilgrastim (Neulasta), filgrastim (Neupogen)) on 21 day cycles - reducing the chemotherapy induced neutropenia and the cited art of Crawford establishes that it is known to administer G-CSF 24 hours after chemotherapy (i.e. day 2 which is within 7 day after the dose of plinabulin).
As for the assertion that one would not arrive at the instant claims for neutrophil support though routine optimization as one in the field did not know that plinabulin produces a neutrophil support effect within 24hours before Applicant’s work, this is not persuasive. The prima facie case of obviousness is not based on routine optimization. The prior art of Huang teaches treating cancer such as NSCLC (non-small cell lung cancer) and lowering the side effects of taxane compound such as decreasing the neutropenia rates (treating neutropenia from taxane/docetaxel) with the administration of plinabulin and G-CSF to a patient wherein the prior art expressly teaches (motivation) the use of both plinabulin and G-CSF for decreasing neutropenia from taxane use and while Huang is silent as to when the G-CSF is administered - it is implicit if not prima facie obvious to administer the G-CSF at its known delivery regimen (i.e. pegfilgrastim 24 hours after chemotherapy which is day 2 and within 7 day after the dose of plinabulin) as established by Crawford with a reasonable expectation of success.
Applicant’s citation of Tonra et al. that plinabulin ameliorates chemotherapy induced neutropenia via a mechanism different from G-CSF which supports its use as an alternative or combinational approach, is fully considered but not persuasive. Tonra et al. is post filing art which merely addresses that the mechanism of action of plinabulin is different from G-CSF which is not unexpected as it is not a G-CSF and supports Huang which already establishes its use for addressing chemotherapeutic induced neutropenia such as from docetaxel and its combinational use with G-CSF. As for the assertion that the art does not appreciate that plinabulin can reduce adverse effects associated with G-CSF and improve the tolerability of full-dose G-CSF treatment, this is fully considered but not persuasive there is no requirement that one of skill in the art would have recognized this effect was present in the disclosure at the time but only that the subject matter is in fact intrinsically present in the prior art reference as the discovery of the a previously unappreciated property or a scientific explantation for the prior art’s functioning does not render the old composition or regimen/method patentably new to the discoverer, so claiming a new yes, function , or unknown property which is intrinsically present does not necessarily make the claim patentable. The effects of the administration of plinabulin with G-CSF such as the reduction of adverse effects associated with G-CSF are intrinsically present as it necessarily flow from the teaching of the applied prior art or the natural result of the combination of elements explicitly disclosed by the prior art, as the same drugs are given in the same time frame to the same cancer patients reducing the chemotherapeutic induced neutropenia.
As for the assertion that that the cited art does not recognize the timing and therapeutic interplay of plinabulin’s early neutrophil support with G-CSF’s delayed effect along with the assertion that G-CSF is used as a secondary or rescue therapy when plinabulin alone is insufficient in Example 3 of Huang, and the assertion of unexpected results with the timing for the plinabulin and G-CSF would provide continuous protection across the neutrophil nadir which is not recognized by the cited art. This is fully considered but not persuasive. Contrary to Applicant’s assertion, Huang does not recite that G-CSF was used as a secondary or rescue therapy in Example 3. It is also moot as Huang expressly teaches the usefulness of G-CSF in some patients where it expressly teaches administration of the combination of plinabulin and G-CSF for neutropenia from the taxane in those patients that required/benefited from the combination which is motivation to use the combination in patients who would require or benefit from it and it is implicit if not prima facie obvious to administer the G-CSF at its known delivery regimen (i.e. pegfilgrastim 24 hours after chemotherapy, day 2 and within 7 days of plinabulin) as established by Crawford with a reasonable expectation of success wherein the timing of the regimen for the plinabulin and G-CSF are met.
It is noted that Applicant is citing Figure 1 from Example 1 which is to docetaxel 75mg/m2 and pegfilgrastim 6mg, docetaxel 75mg/m2 with plinabulin (at 20mg/m2, at 10mg/mm2, at 5mg/m2) which is not commensurate in scope with the breath claimed, and also citing Example 2 which is to breast cancer which is not the elected condition of non-small cell lung cancer - with a decrease in neutropenia grade 3/4 with plinabulin at 20mg/m2 with pegfilgrastim 6mg compared to pegfilgrastim 6mg alone citing Table 3 and Figure 2 which is to docetaxel (75mg/m2) and doxorubicin (50mg/m2) and cyclophosphamide (500mg/m2) every 3weeks which is not the breath claimed. Figure 2 is confusing as it shows a median ANC that is above the grade 3/4 neutropenia line but Table 3 cites that 50% of patient were in grade 3/4 neutropenia wherein how would the median be above the line (verses at or below the line) wherein the Figure 2 appears to be different from Table 3.
As for the assertion that Huang does not suggest the timing of plinabulin effect on neutropenia within 24 hours to allow the drugs to work for unexpected results as the peak of plinabulin is on Day 2-5 when given on Day 1, and the peak of pegfilgrastim is around Day 10 when given on Day 2, so there is a more continuous reduction in neutropenia and other symptoms that one would not predict since the peak of plinabulin could be expected to occur in the second week. This is fully considered but not persuasive as the effects presented are a result of the administration of plinabulin and the pegfilgrastim at the taught and known regimens of the cited prior art - which are additive and not unexpected as asserted by Applicant. Pegfilgrastim has two peaks - one in the 2-5 day window and one at the 10 day window, and the plinabulin has the peak at day 2-5 wherein the effect is additive and not unexpected. Additionally Applicant’s figures for the peak are merely showing what occurred when the combination of plinabulin and pegfilgrastim was administered with docetaxel as exemplified in Huang at the known/taught regimen as established by Crawford. There is no requirement that one of skill in the art would have recognized this effect was present in the disclosure at the time but only that the subject matter is in fact intrinsically present in the prior art reference, and recognition of the unappreciated effects of the administration of the combination already taught in the prior art at its known/taught regimen does not necessarily make the claim patentable. As the discovery of a previously unappreciated property or a scientific explantation of the prior art’s functioning does not render it patentably new to the discover.
Accordingly, the rejection stands.
Claim 70 is rejected under 35 U.S.C. 103 as being unpatentable over Huang (U.S. Pat. Pub. 2016/0250209) in view of Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia) as applied to claims 1,3, 5, 10-11, 17, 19, 22, 30, 33 above, further in view of Dalton et al. (U.S. Pat. Pub. 2013/0034562).
Rejection:
The teachings of Huang in view of Crawford are addressed above, including that plinabulin can be given preferably within 0.5-24 hrs after chemotherapy like taxane [66], and from 10-50 or 20-30 mg/m2 [56].
Wherein while Huang in view of Crawford does not recite the exact claimed time interval and dose of plinabulin recited, it is embraced by the taught range wherein it would be prima facie obvious to optimize within the taught range and arrive at the recited time/dose absent evidence of criticality for the claimed value.
Huang in view of Crawford does not expressly recite the inclusion of doxorubicin and cyclophosphamide with docetaxel, but does teach the use of chemotherapy including docetaxel with plinabulin and G-CSF like Pegfilgrastim (Neulasta) for treating cancer like non-small cell lung cancer.
Dalton et al. teaches that chemotherapy for non-small cell lung cancer is known to include agents like docetaxel, doxorubicin, cyclophosphamide, and combinations thereof (claims 1,3, 6).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include doxorubicin and cyclophosphamide with docetaxel as suggested by Dalton et al. and produce the claimed invention; as it is prima facie obvious to include known chemotherapeutic agents for their additive effect on non-small cell lung cancer for with a reasonable expectation of success absent evidence of criticality for the recited combination.
Claims 16 and 71 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (U.S. Pat. Pub. 2016/0250209) in view of Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia) as applied to claims 1,3, 5, 10-11, 17, 19, 22, 30, 33 above, further in view of Weycker et al. (Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?-abstract only).
Rejection:
The teachings of Huang in view of Crawford are addressed above.
Huang in view of Crawford does not expressly recite the G-CSF drug to be administered at least 48 hours after the administration of the chemotherapy but does teach that it is known to give a single dose of pegfilgrastim 24 hours after chemotherapy to reduce neutropenic complications.
Weycker et al. teaches that neutropenia was higher when the pegfilgrastim was given the same day as chemotherapy verses days 2-4 from chemotherapy completion underscoring the importance of administer to the indicated post chemotherapy schedule (days 2-4 from chemotherapy completion).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to give the pegfilgrastim on day 2-4 from chemotherapy completion as suggested by Weycker et al. and produce the claimed invention; as it is prima facie obvious to deliver the pegfilgrastim at its known schedule for reducing the neutropenia with chemotherapy and to optimize within that range (day 2-4) that overlaps the recited range with a reasonable expectation of success absent evidence of criticality for the claimed values (i.e. day 3, day 4, day 5).
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, 5, 10-11, 17, 19, 22, 30, 33, 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 14-15, 19, 22-25 of U.S. Patent No. 11229642 in view of Huang (U.S. Pat. Pub. 2016/0250209) and Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia).
The patented claims are to a method of reducing neutropenia induced by a chemotherapeutic composition with one or more chemotherapeutic actives including cyclophosphamide and doxorubicin, with the administration of plinabulin; additional claims recite the inclusion of taxanes like docetaxel, to be grade 3 or 4 neutropenia (Grade 4 is <0.5x109/L), and the administration of plinabulin after chemo with limitations (i.e. time of administration) that overlap the instant claimed range wherein even a slight overlap in range establishes a prima facie case of obviousness.
The patented claim do not recite a G-CSF agent and when it is given, or dependent recitations to how much G-CSF is given or type of chemotherapy treatment or the dose of plinabulin, but is directed to a method of treating chemotherapeutic induced neutropenia with plinabulin.
Huang teaches that the combination of plinabulin and a taxane compound like docetaxel for treating cancer such as NSCLC (non-small cell lung cancer) and lowering the side effects of taxane compound such as decreasing the neutropenia rates (treating neutropenia from taxane/docetaxel) at all grades (abstract, [3]). Huang teaches that they can be combined with other drugs for treating cancer such as cisplatin [73]. Huang also teaches Example 3 where patients with non-small cell lung cancer (NSCLC) were treated with docetaxel and then plinabulin (i.e. 2 hours after docetaxel on day 1 at 20mg/m2 and 30mg/m2 doses) and additional G-CSF (Pegfilgrastim (Neulasta), filgrastim (Neupogen)) on 21 day cycles - reducing the neutropenia side effect of the docetaxel in all grades especially >/= Grade 3 neutropenia (>Grade 3 neutropenia includes Grade 4 which is <0.5x109/L see instant specification, [223-227], Table 9). The plinabulin can also preferably be administered within 0.5-24 hrs after chemotherapy like taxane [66], and from 10-50 or 20-30 mg/m2 ([56], see full document specifically areas cited).
Crawford teaches that pegfilgrastim is given once-per-cycle and filgrastim is given daily for the management of chemotherapy-induced neutropenia. Crawford teaches that filgrastim is given daily on an average of 11 daily injections at 5ug/kg/d at 24 hours after treatment with chemotherapy. Crawford also teaches that a single dose of pegfilgrastim given 24 hours after chemotherapy reduce neutropenic complications and the doses used were 30ug/kg (about 2.1mg with 70kg/standard man), 100ug/kg (about 7mg), 300ug/kg (about 21mg) were useful, and that all weight groups were adequately protected with a single 6mg dose of pegfilgrastim (Abstract, Page 25 second column, Fig 2, Conclusion, see full document specifically areas cited).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a G-CSF active like pegfilgrastim or filgrastim with plinabulin at its known regimen of administration timing and doses for known cancers like non-small cell lung cancer and chemotherapies like docetaxel as suggested by Huang and Crawford and produce the claimed invention; as it is prima facie obvious to incorporate a known active that is taught to be combined with plinabulin for the same purpose with a reasonable expectation of success and deliver it in its known useful regimen and dosage with a reasonable expectation of success. It is also prima facie obvious to use the known dose of plinabulin and known G-CSF actives that are also taught to be in combination with plinabulin for known chemotherapy treatments for cancers that induce neutropenia with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments are centered on the assertion that the patented claims do not recite G-CSF or the co-administration of plinabulin with G-CSF with the recited timing, that Huang would not provide motivation to provide the missing features as addressed in the prior art rejection above, that Crawford does not cure the deficiencies, and the assertion of unexpected results. This is fully considered but not persuasive. The arguments to patented claims is against them individually, and one cannot show nonobviousness by attacking the patented claims individually where the rejections are based on combinations of references. As for the assertions to Huang, Crawford, and unexpected results, these are addressed in the prior art rejection above and incorporated herein by reference.
Accordingly, the rejection stands.
Claims 16 and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 14-15, 19, 22-25 of U.S. Patent No. 11229642 in view of Huang (U.S. Pat. Pub. 2016/0250209) and Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia) as applied to claims 1, 3, 5, 10-11, 17, 19, 22, 30, 33, 70 above, further in view of Weycker et al. (Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?-abstract only).
The teachings of the patented claims in view of Huang and Crawford are addressed above.
The patented claims in view of Huang and Crawford does not expressly recite the G-CSF drug to be administered at least 48 hours after the administration of the chemotherapy but does teach that it is known to give a single dose of pegfilgrastim 24 hours after chemotherapy to reduce neutropenic complications.
Weycker et al. teaches that neutropenia was higher when the pegfilgrastim was given the same day as chemotherapy verses days 2-4 from chemotherapy completion underscoring the importance of administer to the indicated post chemotherapy schedule (days 2-4 from chemotherapy completion).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to give the pegfilgrastim on day 2-4 from chemotherapy completion as suggested by Weycker et al. and produce the claimed invention; as it is prima facie obvious to deliver the pegfilgrastim at its known schedule for reducing the neutropenia with chemotherapy and to optimize within that range (day 2-4) that overlaps the recited range with a reasonable expectation of success absent evidence of criticality for the claimed values (i.e. day 3, day 4, day 5).
Claims 1, 3, 5, 10-11, 17, 19, 22, 30, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 19 U.S. Patent No. 12433886 in view of Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia).
The patented claims are to a method of reducing neutropenia induced by a chemotherapeutic composition with one or more chemotherapeutic actives including cyclophosphamide and cisplatin, with the administration of about 10-about 50mg/m2 plinabulin a minute to 24 hours after chemo administration; additional claims recite the inclusion of additional chemotherapeutics, absolute neutrophil count, and the administration of plinabulin after chemo with limitations (i.e. time of administration) that either fall within the instant claimed range or overlap the instant claimed range wherein even a slight overlap in range establishes a prima facie case of obviousness.
The patented claims do not recite a G-CSF agent and when it is given, but is directed to a method of treating chemotherapeutic induced neutropenia with plinabulin.
Crawford teaches that filgrastim and pegfilgrastim are used for decreasing the incidence of neutropenia in chemotherapy patients. Pegfilgrastim is given once-per-cycle and filgrastim is given daily for the management of chemotherapy-induced neutropenia. Crawford teaches that filgrastim is given daily on an average of 11 daily injections at 5ug/kg/d at 24 hours after treatment with chemotherapy. Crawford also teaches that a single dose of pegfilgrastim given 24 hours after chemotherapy reduce neutropenic complications and the doses used were 30ug/kg (about 2.1mg with 70kg/standard man), 100ug/kg (about 7mg), 300ug/kg (about 21mg) were useful, and that all weight groups were adequately protected with a single 6mg dose of pegfilgrastim (Abstract, Page 25 second column, Fig 2, Conclusion, see full document specifically areas cited).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate an active like pegfilgrastim or filgrastim at its known regimen/doses (pegfilgrastim 24 hours after chemotherapy delivery at the known dosages like 6mg and 7mg, and filgrastim 24 hours after chemotherapy to start and daily afterward (an average for 11 days, is 2 or more doses from 24-48 hrs) as suggested by Crawford and produce the claimed invention; as it is prima facie obvious to incorporate a known active that is taught to be useful for the same purpose and to deliver the pegfilgrastim or filgrastim in its known useful regime and in its known useful dosage with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments are centered on the assertion that the claims do not recite G-CSF or the co-administration of plinabulin with G-CSF with the claimed timing, and the assertion of unexpected results. This is fully considered but not persuasive. The arguments to claims are against them individually, and one cannot show nonobviousness by attacking the patented claims individually where the rejections are based on combinations of references. As for the assertions to Crawford and unexpected results, this is not persuasive as the inclusion of another active for its additive effect for the same purpose is prima facie obvious with a reasonable expectation of success and recognition for its additive effect is not an unexpected result.
Accordingly, the rejection stands.
Claims 16 and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 19 U.S. Patent No. 12433886 in view of Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia) as applied to claims 1, 3, 5, 10-11, 17, 19, 22, 30, 33 above, further in view of Weycker et al. (Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?-abstract only).
The teachings of the patented claims in view of Crawford are addressed above.
The patented claims in view of Crawford does not expressly recite the G-CSF drug to be administered at least 48 hours after the administration of the chemotherapy but does teach that it is known to give a single dose of pegfilgrastim 24 hours after chemotherapy to reduce neutropenic complications.
Weycker et al. teaches that neutropenia was higher when the pegfilgrastim was given the same day as chemotherapy verses days 2-4 from chemotherapy completion underscoring the importance of administer to the indicated post chemotherapy schedule (days 2-4 from chemotherapy completion).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to give the pegfilgrastim on day 2-4 from chemotherapy completion as suggested by Weycker et al. and produce the claimed invention; as it is prima facie obvious to deliver the pegfilgrastim at its known schedule for reducing the neutropenia with chemotherapy and to optimize within that range (day 2-4) that overlaps the recited range with a reasonable expectation of success absent evidence of criticality for the claimed values (i.e. day 3, day 4, day 5).
Claims 1, 3, 5, 10-11, 17, 19, 22, 30, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 10596169 in view of Huang (U.S. Pat. Pub. 2016/0250209) and Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia).
The patented claims are to a method of treating grade 3 or 4 (Grade 4 is <0.5x109/L) neutropenia in a subject being administered 75mg/m2 docetaxel (neutropenia induced by docetaxel) with the administration of a dose of 20mg/m2 or 30mg/m2 plinabulin 0.5-72hr after giving the docetaxel; additional claims recite the time frame to be 2 hours after docetaxel. The administration of plinabulin after chemo either fall within the range or embrace the range wherein it is prima facie obvious to optimize within the range and arrive at the claimed values as a means of attaining the desired therapeutic profile.
The patented claim do not recite a G-CSF agent or when it is given or type of chemotherapy treatment, but is directed to a method of treating docetaxel induced neutropenia with plinabulin.
Huang teaches that the combination of plinabulin and a taxane compound like docetaxel for treating cancer such as NSCLC (non-small cell lung cancer) and lowering the side effects of taxane compound such as decreasing the neutropenia rates (treating neutropenia from taxane/docetaxel) at all grades (abstract, [3]). Huang also teaches Example 3 where patients with non-small cell lung cancer (NSCLC) were treated with docetaxel and then plinabulin (i.e. 2 hours after docetaxel on day 1 at 20mg/m2 and 30mg/m2 doses) and additional G-CSF (Pegfilgrastim (Neulasta), filgrastim (Neupogen)) on 21 day cycles - reducing the neutropenia side effect of the docetaxel in all grades especially >/= Grade 3 neutropenia (>Grade 3 neutropenia includes Grade 4 which is <0.5x109/L see instant specification, [223-227], Table 9, see full document specifically areas cited).
Crawford teaches that pegfilgrastim is given once-per-cycle and filgrastim is given daily for the management of chemotherapy-induced neutropenia. Crawford teaches that filgrastim is given daily on an average of 11 daily injections at 5ug/kg/d at 24 hours after treatment with chemotherapy. Crawford also teaches that a single dose of pegfilgrastim given 24 hours after chemotherapy reduce neutropenic complications and the doses used were 30ug/kg (about 2.1mg with 70kg/standard man), 100ug/kg (about 7mg), 300ug/kg (about 21mg) were useful, and that all weight groups were adequately protected with a single 6mg dose of pegfilgrastim (Abstract, Page 25 second column, Fig 2, Conclusion, see full document specifically areas cited).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize pegfilgrastim or filgrastim with plinabulin at its known regimen of administration timing and doses for known cancers like non-small cell lung cancer and chemotherapies like docetaxel as suggested by Huang and Crawford produce the claimed invention; as it is prima facie obvious to use known G-CSF actives that are also taught to be in combination with plinabulin for known chemotherapy treatments for cancers that induce neutropenia and deliver it in its known useful regimen and dosage with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments are centered on the assertion that the patented claims are distinct from the pending claims for the same reasons are novel over Huang in view of Crawford as argued above. This is fully considered but not persuasive as addressed above.
Accordingly, the rejection stands.
Claim 70 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 10596169 in view of Huang (U.S. Pat. Pub. 2016/0250209) and Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia) as applied to claims 1, 3, 5, 10-11, 17, 19, 22, 30, 33 above, further in view of Dalton et al. (U.S. Pat. Pub. 2013/0034562).
The teachings of the patented claims in view of Huang and Crawford are addressed above.
The patented claims in view of Huang and Crawford does not expressly recite the inclusion of doxorubicin and cyclophosphamide with docetaxel, it does teach the use of docetaxel and the administration of plinabulin after docetaxel from 0.5-72 hours (i.e. 30 min) with G-CSF 24 hours after chemotherapy such as for cancer like non-small cell lung cancer, wherein it would be obvious to optimize when to administer the plinabulin within the patented range absent evidence of criticality of the 30min value.
Dalton et al. teaches that chemotherapy for non-small cell lung cancer is known to include agents like docetaxel, doxorubicin, cyclophosphamide, and combinations thereof (claims 1,3, 6).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include doxorubicin and cyclophosphamide with docetaxel as suggested by Dalton et al. and produce the claimed invention; as it is prima facie obvious to include known chemotherapeutic agents for their additive effect on non-small cell lung cancer for with a reasonable expectation of success absent evidence of criticality for the recited combination.
Claims 16 and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 10596169 in view of Huang (U.S. Pat. Pub. 2016/0250209) and Crawford (Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia) as applied to claims 1, 3, 5, 10-11, 17, 19, 22, 30, 33 above, further in view of Weycker et al. (Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?-abstract only).
The teachings of the patented claims in view of Crawford are addressed above.
The patented claims in view of Crawford does not expressly recite the G-CSF drug to be administered at least 48 hours after the administration of the chemotherapy but does teach that it is known to give a single dose of pegfilgrastim 24 hours after chemotherapy to reduce neutropenic complications.
Weycker et al. teaches that neutropenia was higher when the pegfilgrastim was given the same day as chemotherapy verses days 2-4 from chemotherapy completion underscoring the importance of administer to the indicated post chemotherapy schedule (days 2-4 from chemotherapy completion).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to give the pegfilgrastim on day 2-4 from chemotherapy completion as suggested by Weycker et al. and produce the claimed invention; as it is prima facie obvious to deliver the pegfilgrastim at its known schedule for reducing the neutropenia with chemotherapy and to optimize within that range (day 2-4) that overlaps the recited range with a reasonable expectation of success absent evidence of criticality for the claimed values (i.e. day 3, day 4, day 5).
Conclusion
Claims 1, 3, 5, 10-11, 16-17, 19, 22, 30, 33, 70-71 are rejected.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
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