DETAILED ACTION
Claims 1-4 and 6-19 were pending. Applicant’s reply filed 5/15/2026 is acknowledged, no claims have been amended.
Claims 1-4 and 6-19 are pending.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 5/15/2026 has been entered.
THIS ACTION IS MADE FINAL
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Priority
The application, filed 12/7/2020 claims Priority from Provisional Application 62/944,359, filed 12/5/2019.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 6-8, 12-15, and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vacirca et al. “An open-label, dose-ranging study of Rolontis, a novel long-acting myeloid growth factor, in breast cancer,” Cancer Medicine 2018; 7(5):1660–1669 published March 23, 2018.
Claim 1 is directed towards a method treating or preventing the condition characterized by compromised white blood cell production in a patient in need thereof, the method comprising administering an effective amount of Eflapegrastim within a period of less than 24 hours after the patient is administered a chemotherapeutic agent or receives a radiotherapy.
Vacirca teaches many effective chemotherapy regimens induce myelosuppressive side effects that can result in treatment delays, dose reductions, and an overall inability to complete treatment, which may compromise clinical outcomes, page 1661, column 1, para 1. Vacirca teaches chemotherapy-induced neutropenia can progress to febrile neutropenia.
Vacirca teaches that the patients were treated with docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) by IV infusion every 3 weeks for up to four cycles. This chemotherapy is characterized by compromising white blood cell production in a patient.
Vacirca teaches treating patients with breast cancer. On Day 1 of each of four cycles with adjuvant/neo-adjuvant docetaxel and cyclophosphamide (TC). On Day 2 of each cycle patients received a single subcutaneous dose of either eflapegrastim (Rolontis) (45, 135, or 270 μg/kg) or pegfilgrastim (6 mg) in a 1:1 ratio. On Day 2 of each cycle (approximately 24 h after TC chemotherapy), patients administered their assigned study treatment with either eflapegrastim or pegfilgrastim.
As seen in the reference:
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The teaching of Vacirca anticipates the instant claim 1 as eflapegrastim is given approximately 24 h after TC chemotherapy to prevent chemotherapy-induced neutropenia. “Approximately 24 h after TC chemotherapy,” envisages a short time before, 24 hours exactly, and a short time after (as species). One of ordinary skill in the art would understand with scheduling patients for therapy one may show up a few hours before or after the chemotherapy or myeloid growth factor therapy appointment time and therefore one would at once envision the time period of 22-26 hours after the chemo (as a range). Therefore the reference anticipates the instant claims as one envisages a short time before 24 hours and Applicant’s claim encompasses 23 hours, 59 minutes and 59 seconds, which is before 24 hours.
Instant claims 2 and 3 state, wherein the condition characterized by compromised white blood cell production is selected from the group consisting of chemotherapy-induced neutropenia…
Vacirca teaches chemotherapy-induced neutropenia, see Table 3, page 1666.
Instant claim 4 requires wherein the method reduces the duration of chemotherapy-induced neutropenia. This is also seen in Table 3.
Instant claim 6 requires that administering the effective amount of Eflapegrastim reduces the duration of an absolute neutrophil count of less than about 0.5x109/L in the patient to less than about 6 hours, about 12 hours, or 24 hours. This is clearly seen in Figure 2, A, Cycle 1, the ACN is not below the required level.
Instant claim 7 requires wherein administering the effective amount of Eflapegrastim prevents the absolute neutrophil count in the patient from reaching less than about 0.5x 109/L. This is clearly seen in Figure 2, A, Cycle 2, the ACN is not below the required level.
Instant claim 8 requires wherein upon administration of the effective amount of Eflapegrastim, an absolute neutrophil count of the patient increases from the first occurrence of less than about 0.5x 109/L to greater than or equal to about 1.5x 109/L within less than about four days, about seven days, or about ten days. This is clearly seen in Figure 2, A, Cycle 1, the ACN is not below the required level.
Instant claim 12 The method of claim 1, wherein the chemotherapeutic agent is a myelosuppressive chemotherapeutic agent. Instant claim 13 method of claim 12, wherein the myelosuppressive chemotherapeutic agent is selected from the group consisting of docetaxel, cyclophosphamide, doxorubicin, etoposide, cisplatin, paclitaxel, topotecan, vincristine, methylprednisolone, cytarabine, and combinations thereof.
Vacirca teaches patients were treated with docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) by IV infusion every 3 weeks for up to four cycles, page 1662.
Instant claim 14 chemotherapeutic agent or the radiotherapy-induced neutropenia is the result of a treatment for a cancer selected from the group consisting of breast cancer, non-small cell lung cancer, small cell lung cancer, ovarian cancer, sarcoma, urothelial cancer, germ cell tumors and non- Hodgkin's lymphoma.
Vacirca teaches most patients were female (98%) and White (95%), and the majority (84%) had invasive ductal carcinoma. Disease stage at the time of breast cancer diagnosis was Stage II (57%), Stage I (20%), or Stage III (21%), with two patients (1%) diagnosed as Stage IV, page 1663, column 1.
Instant claim 15 method of claim 1, wherein administering an effective amount of Eflapegrastim comprises administering parenterally from about 2 to 18 mg of Eflapegrastim.
Vacirca teaches patients weight of the patients were in a range, but some were between 65-75 kg. This calculated the dose of (45, 135, or 270 μg/kg) to 2.9, 8.7, 17.6mg for 65 kg patient. Therefore Vacirca anticipates the 2-18 mg range.
Instant claim 17 method of claim 3, wherein the chemotherapy-induced neutropenia is treated with the use of a chemotherapeutic agent. Instant claim 18 method of claim 17, wherein the chemotherapeutic agent is a myelosuppressive chemotherapeutic agent. Instant claim 19 method of claim 18, wherein the myelosuppressive chemotherapeutic agent is selected from the group consisting of docetaxel, cyclophosphamide, doxorubicin, etoposide, cisplatin, paclitaxel, topotecan, vincristine, methylprednisolone, cytarabine, and combinations thereof.
Vacirca teaches patients were treated with docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) by IV infusion every 3 weeks for up to four cycles, page 1662, anticipating claims 17-19.
Response to Arguments: Anticipation: Applicant argues that the teaching in the art of “On Day 2 of each cycle (approximately 24 h after TC chemotherapy), patients administered their assigned study treatment with either Rolontis or pegfilgrastim,” does not anticipate “administering an effective amount of Eflapegrastim within a period of less than 24 hours after the patient is administered a chemotherapeutic agent or receives a radiotherapy.” Note, Rolontis is Eflapegrastim.
Applicant states, “the Office's claim construction is beyond the broadest reasonable interpretation. ‘The broadest-construction rubric coupled with the term 'comprising' does not give the PTO an unfettered license to interpret claims to embrace anything remotely related to the claimed invention. For at least that reason, the rejection is improper and should be withdrawn.”
The Examiner constructs the claim to encompass giving eflapegrastim at the same time to 23 hours, 59 minutes and 59 seconds after the administration (start) of chemotherapy (note an IV infusion of docetaxel takes approximately 1 hour) a range. This is not unfettered embrace of anything remotely related to the claimed invention.
The Examiner interprets the art for what it at once envisages by stating “approximately 24 h after TC chemotherapy.” One envisages a short time before, 24 hours exactly, and a short time after (as species). One of ordinary skill in the art would understand with scheduling patients for therapy one may show up a few hours before or after the chemotherapy or myeloid growth factor therapy appointment time and therefore one would at once envision a short time before, 24 hours exactly, and a short time after (as species) and the time period of 22-26 hours after the chemo. Moreover, a doctor or IV technician would not delay treatment as they would understand that giving the eflapegrastima minutes before 24 hours wouldn’t matter, as the pharmacology variance is enough that a few minutes or hours would not alter the outcome of treatment. Again, the time period of “shortly before 24 hours” is envisaged and anticipatory. As the species will anticipate a claim to a genus. MPEP 2131.02(III).
As to the discussion of the range taught/envisaged, 22-26 hours after. MPEP 2131.03, Anticipation of Ranges, When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute." What constitutes a "sufficient specificity" is fact dependent. If the claims are directed to a narrow range, and the reference teaches a broader range, other facts of the case, must be considered when determining whether the narrow range is disclosed with "sufficient specificity" to constitute an anticipation of the claims. Compare ClearValue Inc. v. Pearl River Polymers Inc., 668 F.3d 1340, 101 USPQ2d 1773 (Fed. Cir. 2012) with Atofina v. Great Lakes Chem. Corp, 441 F.3d 991, 999, 78 USPQ2d 1417, 1423 (Fed. Cir. 2006). The question of "sufficient specificity" is similar to that of "clearly envisaging" a species from a generic teaching. See MPEP § 2131.02.
In this case given the pharmacology variance, the variance in patient response, and the simple variance in running an IV infusion clinic, one would clearly find that the art teaches the range or 22-26 hours which would be sufficient to anticipate the instant claim.
Applicant states, “the Office's reliance on "logic[] and [reason]" amounts to a rejection that the claims are inherently anticipated. But to establish inherency, the missing descriptive matter must necessarily be present in the thing described in the reference². Inherency may not be established by probabilities or possibilities. Moreover, the mere fact that a certain thing may result from a given set of circumstances is not sufficient. As acknowledged by the Office, the same day administration recited in the present claims is not necessarily present. As such, for that additional reason, the rejection should be withdrawn.
This argument seems misplaced, as noted above. The Examiner is simply trying to ask, what is taught by the art in the context of having skill in the art. The Examiner simply used their best judgement to arrive at what the art “at once envisages.” The Examiner sees the art teaching, a short time before, 24 hours exactly, and a short time after (as species) and 22-26 hours as a range.
Applicant argues claim 6 specifically in the anticipation rejection, stating, “Regarding the rejection of claim 6, the Office alleges that Vacirca anticipates that administering the effective amount of eflapegrastim reduces the duration of an absolute neutrophil count of less than 0.5 X 10⁹/L in the patient to less than about 6 hours, about 12 hours, or 24 hours, stating that in Figure 2, A, Cycle 1 of Vacirca, the ANC does not fall below the claimed level.” Applicant believes the Table is insufficient to show the duration of an absolute neutrophil count below the level in less than 6 hours.
Claim 6 states, “[t]he method of claim 1, wherein administering the effective amount of Eflapegrastim reduces the duration of an absolute neutrophil count of less than about 0.5x109L in the patient to less than about 6 hours, about 12 hours, or 24 hours.”
For background, the art recognizes that neutropenia is classified based on the Absolute Neutrophil Count (ANC), and Severe Neutropenia in an ANC below 0.5x109L. This signifies a significantly compromised immune system, placing individuals at a high risk for serious infections, requiring immediate medical attention.
To put in laymen’s terms claim 6 requires the “effective amount” of Eflapegrastim to reduce sever neutropenia to less that one day. This claim encompasses during any cycle, and over any two time points as long as they encompass the required time period.
The Examiner believes this is shown in Figure 2, as the higher dose of Eflapegrastim in the second, third, and fourth cycle, panels B-D, the ACN never drops below 0.5. This is clearly illustrated. However to show the point, one can turn to Table 2, which records duration of severe neutropenia (DSN). One can see that in cycle 1, the medium and higher dose the DSN is below 1, and in the cycles 2-4 the DSN are all below 1 except the lowest dose in Cycle 4. Therefore one would see the “effective amount” of 135 and 270 μg/kg are anticipatory to this claim as the days (24 hour time period) is below 1 for of severe neutropenia.
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This rejection is in regards to claims 9-11 which require “the effective amount of Eflapegrastim is administered concomitantly with the chemotherapeutic agent or the radiotherapy,” (instant claim 9). Instant claim 10 requires “wherein the effective amount of Eflapegrastim is administered within about 0.5 hours, about 3 hours, or about 5 hours after the administration of the chemotherapeutic agent or the receipt of the radiotherapy.” Instant claim 11 requires has overlap with the timing of claim 10.
Claims 1-4 and 6-19 are rejected under 35 U.S.C. 103 as being unpatentable over Vacirca et al. “An open-label, dose-ranging study of Rolontis, a novel long-acting myeloid growth factor, in breast cancer,” Cancer Medicine 2018; 7(5):1660–1669 published March 23, 2018; and Lokich “Same-Day Pegfilgrastim and Chemotherapy,” Cancer Investigation, 23:573–576, 2005.
This rejection is in regards to claims 9-11 which require “the effective amount of Eflapegrastim is administered concomitantly with the chemotherapeutic agent or the radiotherapy,” (instant claim 9). Instant claim 10 requires “wherein the effective amount of Eflapegrastim is administered within about 0.5 hours, about 3 hours, or about 5 hours after the administration of the chemotherapeutic agent or the receipt of the radiotherapy.” Instant claim 11 requires has overlap with the timing of claim 10.
Claim 1 is directed towards a method treating or preventing the condition characterized by compromised white blood cell production in a patient in need thereof, the method comprising administering an effective amount of Eflapegrastim within a period of less than 24 hours after the patient is administered a chemotherapeutic agent or receives a radiotherapy.
This rejection starts by discussing instant claims 9-11 which require “the effective amount of Eflapegrastim is administered concomitantly with the chemotherapeutic agent or the radiotherapy,” (instant claim 9). Instant claim 10 requires “wherein the effective amount of Eflapegrastim is administered within about 0.5 hours, about 3 hours, or about 5 hours after the administration of the chemotherapeutic agent or the receipt of the radiotherapy.” Instant claim 11 has overlap with the timing of claim 10, but also allows for about 12 hours after.
Vacirca is directed to a study comparing the effects of eflapegrastim and pegfilgrastim. The 102 above teaches most of the required limitations, the reference however doesn’t teach giving the long-acting myeloid growth factor (eflapegrastim or pegfilgrastim) on the same day as the chemotherapy, which is desirable as the patient would not have to visit the office on back-to-back days to get two IV injections. If one could do both treatments on one day, this would be simpler for the patient and the clinic for patient compliance.
Vacirca teaches treating patients with breast cancer. On Day 1 of each of four cycles with adjuvant/neo-adjuvant docetaxel and cyclophosphamide (TC). On Day 2 of each cycle patients received a single subcutaneous dose of either eflapegrastim (Rolontis) (45, 135, or 270 μg/kg) or pegfilgrastim (6 mg) in a 1:1 ratio. On Day 2 of each cycle (approximately 24 h after TC chemotherapy), patients administered their assigned study treatment with either eflapegrastim or pegfilgrastim.
Vacirca shows the comparison of the 2 drugs in Figure 2.
Figure 2.
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In Figure 2, one can see that the clinically efficacious and safe dose of pegfilgrastim (6 mg) has similar efficacy to a dose between 45 and 135 micrograms/kg of eflapegrastim (assuming a 65 kg patient the dose would be between 2.9 mg and 8.8 mg). The two compounds have comparable profiles in the ANC level, the main indicator of efficacy in this drug space.
Looking at all the Tables 2, 3, 4, and 5 one confirms the equivalence of the 2 compounds in treating/preventing chemotherapy-induced neutropenia.
Table 2 (Duration of severe neutropenia (evaluable population):
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Table 3 (Efficacy):
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Table 4 and 5 discuss adverse events, both treatment-emergent and treatment-related.
Table 4:
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Looking at these data, one clearly sees two treatments having equivalence in the art when used to treat chemotherapy-induced neutropenia when administered ~24h after chemotherapy.
Table 2 shows the only point of known superiority (highlighted) from this study, that is only in the first Cycle, at the highest dose tested, eflapegrastim showed a significant difference (P-value 0.023) in duration of severe neutropenia. Eflapegrastim (highest dose) showed a “mean days of severe neutropenia” of 0.03 ± 0.17 compared to pegfilgrastim with 0.31 ± 0.82. Therefore one would expect at the higher dose that eflapegrastim, with its known increased clinical potency, see page 1661, column 2, para 1.
Therefore this reference teaches eflapegrastim and pegfilgrastim as equivalents in the art. Both drugs are long-acting myeloid growth factors, both drugs have demonstrated similar in vitro activity and similar pharmacokinetic (PK) profiles, see page 1661, column 2, para 1. The compounds are also known to be somewhat different, as eflapegrastim in known as a more potent alternative to pegfilgrastim that provides clinical benefits at a lower G-CSF dose. As such one would be able to substitute pegfilgrastim with eflapegrastim with its known higher potency be able to predict a potentially lower dose for similar efficacy.
The Vacirca reference does not teach the administration of eflapegrastim well before 24 h (only approximately 24 hours later), or same day as chemotherapeutic agent or receives a radiotherapy (required by claims 9-11).
Lokich teaches same day pegfilgrastim (the older long-acting myeloid growth factor) in chemotherapy. Lokich states pegylated filgrastim (pegfilgrastim) is recommended to be administered not less than 24 hours following chemotherapy and not less than 14 days prior to chemotherapy based on the theoretic concern that marrow suppression would be accentuated. This schedule of usage for pegfilgrastim may compromise its application for weekly chemotherapy schedules. Lokich compared the “24h later” treatment with the “same day treatment.” Lokich teaches pegfilgrastim can be given safely simultaneously with chemotherapy in weekly chemotherapy schedules.
Lokich quoted below, note pegfilgrastim is pegylated filgrastim:
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Given that eflapegrastim and pegfilgrastim are taught as equivalents in the art (Vacirca), it is obvious to substitute eflapegrastim and pegfilgrastim and expect similar results. Therefore, one would find it obvious to dose eflapegrastim on the same day as the chemotherapeutic (Lokich) because one would be motivated to be more efficient with scheduling the patient to come into the office for treatment. One would expect/predict the drugs to effectively treat neutropenia as they both are shown to effectively do so in the art. Therefore, the instant claims are obvious at filing.
In regards to claim instant claim 16, which requires a dose of eflapegrastim to be 13.2mg administered parenterally.
Vacirca teaches patients on Day 2 of each cycle patients received a single subcutaneous dose of eflapegrastim (Rolontis) (45, 135, or 270 μg/kg). Vacirca also teaches patients weight were in a range, but some were varied and some patients were between 65-75 kg. This calculated the dose of (45, 135, or 270 μg/kg) to 2.9, 8.7, 17.6mg for 65 kg patient. One can get to 13.2 mg in a few obvious ways, either the patient weighs 48.88 kg / 108 pounds or the patient could weigh 97.77 kg / 215 pounds, which is well within the range of the human condition, or one could simply adjust the dose to achieve better efficacy. The dose for a 65 kg person would be 203 μg/kg, which again is within the range taught by Vacirca that has efficacy. Vacirca also states, “Based on these results, a dose of 13.2 mg/0.6 mL/dose, equivalent to 3.6 mg G-CSF, was selected for the Phase 3 development program,” see page 1668, column 2, 3rd para. Given the teaching in the art which shows the range to encompass the instantly claimed dose, and since the dose is known to be result effective, the doctor will always attempt to balance efficacy to risk, the instantly claimed dose is obvious.
See MPEP 2144.05. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
Response to Arguments: Obviousness: Applicant argues the Office’s rejection lacks factual basis. The facts are as follows: (Vacirca) teaches both eflapegrastim and pegfilgrastim are efficacious in preventing DSN, when having chemo on day 1, then approximately 24 hours later having either granulocyte-colony stimulating factor. Lokich showed that while this practice, dosing pegfilgrastim approximately 24 hours later, was generally accepted, there was motivation to do the concomitant dosing to avoid the patient having 2 appointments on back-to-back days and to reduce the burden on the patient and clinic. Lokich shows that concomitant dosing of pegfilgrastim is safe, effective, and improved patient monitoring and reduced the burden to the patient.
The question then is simple, since the art shows a clinical comparison (Vacirca) between eflapegrastim and pegfilgrastim in dosing approximately 24 hours later, and finds eflapegrastim “demonstrated noninferiority at the 135 μg/kg dose and statistical superiority in DSN at the 270 μg/kg dose when compared to pegfilgrastim.” One would be motivated to do the same substitution in the concomitant delivery taught by Lokich with eflapegrastim because it would be less burden on the patient. Moreover, one would expect noninferiority or superiority based on the dosing level and the known properties of the 2 drugs. Making the outcome predictable. Therefore there are no missing facts and Applicant’s argument is not persuasive.
Applicant states, “the inventors have discovered that a same-day dosing regimen for a long-acting G-CSF can reduce patient burden while providing comparable or superior efficacy in treating neutropenia.” The problem is that Lokich teaches that a same-day dosing regimen for a long-acting G-CSF (pegfilgrastim) can reduce patient burden while providing comparable efficacy in treating neutropenia. That’s the exact teaching in the art. As such Applicant did not discover this fact, this fact was known.
Next Applicant points to the teaching of Barrett. Stating that the post priority reference compares the duration of neutropenia (DN) with eflapegrastim or pegfilgrastim at 0, 2, 5, or 24 hours post chemotherapy. Applicant doesn’t point to anything specific in Barret to address, just that the comparison was made.
Applicant points to the Specification data, stating
“at both clinical dose and 1/6 clinical dose, as the interval between the chemotherapy and the test article being administered (e.g., eflapegrastim and pegfilgrastim) became shorter (5 hours, 2 hours, and concomitant), the DN (duration of neutropenia) of pegfilgrastim increased to 1.4~2.4 days. On the other hand, the DN of eflapegrastim increased only slightly to 0.6 days (see, Tables 9 and 10 of the application). That is in line with Barrett submitted previously (and summarized below). Those data demonstrate both the superiority of eflapegrastim as a result of its increased in vivo duration and that dosing regimens prior to 24 hours have unexpected results unanticipated by the prior art. Therefore, a person of skilled in the art would not easily derive the same-day administration of eflapegrastim.”
Firstly this is data is in a rat and only for the 1st cycle of chemo. The claims are directed to any patient (any animal). The claims encompass every cycle of treatment, and as noted in Vacirca the only difference might be in the first cycle, yet this is a known difference (not unexpected). Again the eflapegrastim is known to be more potent (Vacirca). Moreover the data in Barrett and the Specification never did a dose range for both drugs in comparison over many cycles. The data presented by Applicant is incomplete in reference to the instant claims, and one is unable to determine if these results are truly unexpected. Again the increased potency was known. Therefore one would predict a more robust response in ACN, which is what is seen. Therefore the increased ACN by definition leads to less days of neutropenia. Based on the art of record this all seems predictable from the known properties of the known compound used for its known indication.
Applicant lastly argues an unexpected property of eflapegrastim having greater bone marrow resident time which provided a pharmacodynamic advantage over pegfilgrastim, translating into shortened duration of neutropenia. The problem here is significance and “unexpected.” Firstly there seems to be no significant superior result over the entire dose range, in all patients, and specifically over all cycles of chemotherapy. More importantly the art already knew of this result, as Vacirca states eflapegrastim “demonstrated noninferiority at the 135 μg/kg dose and statistical superiority in DSN at the 270 μg/kg dose when compared to pegfilgrastim (in cycle 1 only).” Therefore the increased potency was known in the art, and therefore this is not unexpected. As such, Applicants have not met their burden of demonstrating and explaining the alleged unexpected results, let alone placing the claims commensurate in scope with such results. MPEP 716.02.
Applicant again argues claim 6 specifically, stating:
“Regarding the rejection of claim 6 under 35 U.S.C. § 103, Applicant has discussed above that Vacirca does not anticipate that administering eflapegrastim reduces the duration of an absolute neutrophil count of less than about 0.5x10⁹/L in the patient to less than about 6 hours, about 12 hours, or 24 hours. Lokich does not discuss eflapegrastim, and furthermore does not report numbers for neutrophil counts in hours after dosage. As such, Lokich is insufficient to fix the deficiencies of Vacirca.”
Firstly, as noted in the anticipation rejection Vacirca teaches this at Figure 2, A, Cycle 1, so such a teaching is not required by Lokich. To reiterate: Claim 6 states, “[t]he method of claim 1, wherein administering the effective amount of Eflapegrastim reduces the duration of an absolute neutrophil count of less than about 0.5x109L in the patient to less than about 6 hours, about 12 hours, or 24 hours.”
For background, the art recognizes that neutropenia is classified based on the Absolute Neutrophil Count (ANC), and Severe Neutropenia in an ANC below 0.5x109L. This signifies a significantly compromised immune system, placing individuals at a high risk for serious infections, requiring immediate medical attention.
To put in laymen’s terms, claim 6 requires the “effective amount” of Eflapegrastim to reduce severe neutropenia to less that one day. This claim encompasses during any cycle, and over any two time points as long as they encompass the required time period.
The Examiner believes this is shown in Figure 2, as the higher dose of Eflapegrastim in the second, third, and fourth cycle, panels B-D, the ACN never drops below 0.5. This is clearly illustrated. However to show the point, one can turn to Table 2, which records duration of severe neutropenia (DSN). One can see that in cycle 1, the medium and higher dose the DSN is below 1, and in the cycles 2-4 the DSN are all below 1 except the lowest dose in Cycle 4. Therefore one would see the “effective amount” of 135 and 270 μg/kg meet the limitation to the effective amount as required by claim 6.
Lastly, this claim only limits the “effective amount” as the result of “reduc[ing] the duration of an absolute neutrophil count of less than about 0.5x109L in the patient to less than about 6 hours, about 12 hours, or 24 hours,” is simply a recitation of the result of treatment. MPEP 2111.04 states "a ‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.’ Id. However, the court noted that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). In this case the dose of the drug is taught in the art, the effective amount. As such giving the patient undergoing chemo, the drug at an the known effective amount will result in this outcome claimed by Applicant. As such this claim is obvious.
Conclusion
No claims allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/ Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629
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