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 .
Claims Status
The amendments and remarks filed 05/06/2025 are acknowledged.
Claims 35, 76, 79-80, 83, 86, and 88 are amended.
Claims 1-34, 36-71, and 85 are cancelled.
Claims 89-91 are new.
Claims 35, 72-84, and 86-91 are pending and under examination.
Withdrawn
The rejections of claims 53 and 54 under 35 U.S.C. 112(b) are withdrawn. Applicant has cancelled the claims to overcome the rejections.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/06/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Maintained Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 has been modified solely to address the amendments to claims 35, 76, 79-80, 83, 86, and 88, requiring that the subject is human.
Claims 35, 72-74, 79-84, and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., 2016 (02/12/2025 PTO-892), Guo et al., 2015 (02/12/2025 PTO-892), and Goodrich et al, 2013 (02/12/2025 PTO-892).
Regarding claims 35 and 72, Chen teaches administering the antiepileptic agent levetiracetam (LEV) infusion for one week after fluid percussion injury (FPI; brain insult) and seizures induced by kainic acid (KA) [see Abstract]. Chen further teaches that severity of seizures was enhanced in early post-injury seizures induced by KA, but that the exacerbation of seizure severity could be ameliorated by levetiracetam infusion [see Abstract]. Chen also teaches that early post injury seizures exacerbate susceptibility and severity of post traumatic seizures and increase neuronal degeneration in the CA1 layer of the hippocampus (epileptogenesis) but that these changes are partially reversed by LEV infusion after injury [see Abstract]. Chen further teaches that the prophylactic effects of LEV may decrease the severity of early seizures after fluid percussion injury, which may decrease epileptogenesis and seizure neuronal degeneration extent via several pathways [page 588, right column, first paragraph]. Since Chen teaches that levetiracetam had therapeutic effects (i.e. decreases the severity of early seizures after fluid percussion injury, which may decrease epileptogenesis and seizure neuronal degeneration extent via several pathways), then a therapeutically effective amount of the levetiracetam was necessarily administered.
However, Chen does not teach administering atorvastatin and ceftriaxone in combination with the levetiracetam in a human.
Guo teaches administering statins, specifically atorvastatin to 96.4% of the study population, to patients (human) before stroke and in the acute phase, which is the initiation of statins within 3 days after stroke (brain injury) onset and continuing for at least 3 days [page 702, left column, fifth paragraph-right page, fourth paragraph]. Guo also teaches that the use of stains, i.e. atorvastatin, in the acute phase could reduce the risk of post-stroke early-onset seizures (ES) and also reduce the risk of poststroke epilepsy (PSE) (i.e. treat epileptogenesis) [page 704, left column, third paragraph] and that statins are associated with a lower likelihood of epilepsy [page 704, right column, first paragraph]. Since Guo teaches that the atorvastatin treatment had therapeutic effects (i.e. reduce the risk of post-stroke early-onset seizures (ES) and also reduce the risk of poststroke epilepsy (PSE)) then a therapeutically effective amount was necessarily administered.
Goodrich teaches that 7 days after TBI induction in the rat lateral fluid percussion injury TBI model, glutamate transporter 1 (GLT-1) expression was reduced by 29% in the ipsilesional cortex, but the loss of the GLT-1 expression was reversed by treatment with ceftriaxone [see Abstract]. Goodrich also teaches that ceftriaxone treatment also decreased the level of regional glial fibrillary acid protein (GFAP) expression by 43% in the lesioned cortex, and 12 weeks after injury, reduced cumulative post-traumatic seizure duration, suggesting a potential role for ceftriaxone in treatment of epileptogenic TBI [see Abstract]. Since Goodrich teaches that the ceftriaxone treatment had therapeutic effects (i.e. reduced cumulative post-traumatic seizure duration, suggesting a potential role for ceftriaxone in treatment of epileptogenic TBI) then a therapeutically effective amount of the ceftriaxone was necessarily administered.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combined the levetiracetam of Chen, the atorvastatin of Guo, and the ceftriaxone of Goodrich, into one pharmaceutical composition to treat epileptogenesis in a human after a brain insult. One would have been motivated to have combined the levetiracetam, atorvastatin, and ceftriaxone into a single pharmaceutical composition to treat epileptogenesis in a human after a brain insult because all are known to have antiepileptogenic effects. This follows the logic of
MPEP 2144.06 which states “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the separate, known compositions of levetiracetam, atorvastatin, and ceftriaxone into one single composition for the same purpose of treating epileptogenesis in a human after a brain insult. One further would have been motivated to have combined the three agents into one single composition for the ease of administration.
Claims 73 and 74 are included in this rejection because since Chen teaches that the levetiracetam is administered by infusion (i.e. intravenously) [see Abstract] than the levetiracetam would necessarily would be a solution. This is evidenced by Lyseng-Williamson et al., 2011 (02/12/2025 PTO-892) that teaches levetiracetam is in the form of a solution for intravenous infusion [page 506, right column, third paragraph].
Claims 79-81 is included in this rejection because Chen teaches that the levetiracetam is administered by infusion (i.e. intravenously; parenteral administration) [see Abstract].
Claims 82-84 are included in this rejection because Chen teaches that the infusion was administered for one week after FPI (i.e. 7 days) [see Abstract]. Further, Goodrich teaches that the ceftriaxone is administered for 7 days after TBI [page 1437, left column, second paragraph]. Specifically regarding claim 82, since Chen teaches that the levetiracetam was administered for one week after FPI, and Goodrich teaches that the ceftriaxone was administered for 7 days after TBI, the Examiner is interpreting this as administering the levetiracetam and/or ceftriaxone within 24 hours of the brain insult (i.e. FPI).
Claim 88 is included in this rejection because Goodrich teaches that the ceftriaxone is administered at 200 mg/kg daily (i.e. 1 time per day) [see Abstract].
Claims 35, 72-76, 79-84, and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., 2016 (02/12/2025 PTO-892), Guo et al., 2015 (02/12/2025 PTO-892), and Goodrich et al, 2013 (02/12/2025 PTO-892), as applied to claims 35, 72-74, 79-84, and 88 above, and further in view of Lyseng-Williamson, 2011 (02/12/2025 PTO-892) and Mylan, 2016 (02/12/2025 PTO-892).
The teachings of Chen, Guo, and Goodrich are above.
However, Chen, Guo, and Goodrich do not specifically teach that the solution comprises 5 mg/mL to 50 mg/mL of the levetiracetam and 0.1 mg/mL to 1.0 mg/mL of the atorvastatin or that 10 mL to 50 mL of the solution is administered to the subject 1 time per day.
Regarding claims 75-76, Lyseng-Williamson teaches administering 1000-3000 mg/day of levetiracetam as a therapy to treat the onset of seizures [page 496, left column, fourth paragraph – right column, second paragraph].
Mylan teaches that Lorsat (i.e. atorvastatin) can be administered within the dosage range of 10-80 mg/day as a single daily dose [page 2, sixth paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have formulated a solution comprising 25 mg/mL of levetiracetam and 1.0 mg/mL of atorvastatin, and administering 50 mL of the solution 1 time per day. One would be motivated to formulate a solution comprising levetiracetam and atorvastatin at these concentrations because Lyseng-Williamson teaches that 1000 mg/day is an acceptable dose of levetiracetam and Mylan teaches that 10 mg/day is an acceptable dose of atorvastatin (1000mg/40 mL = 25 mg/mL and 10mg/10mL = 1 mg/mL). MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.” Thus, one would want to administer 50 mL of this solution once per day to give the dose of 1000 mg of levetiracetam and 10 mg of atorvastatin to the subject needing treatment because these are known doses for known therapeutics in the art, and therefore would have a reasonable expectation of success.
Claims 83 is included in this rejection because Lyseng-Williamson teaches a 12 week (i.e. 3 months) treatment phase for levetiracetam [page 497, right column, first paragraph and Table III).
Claims 35, 72-74, 77, 79-84, and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., 2016 (02/12/2025 PTO-892), Guo et al., 2015 (02/12/2025 PTO-892), and Goodrich et al, 2013 (02/12/2025 PTO-892), as applied to claims 35, 72-74, 79-84, and 88 above, and further in view of Brogden et al., 2012 (02/12/2025 PTO-892).
The teachings of Chen, Guo, and Goodrich are above.
However, Chen, Guo, and Goodrich do not specifically teach that the daily dose of ceftriaxone is 2 g to 4 g.
Regarding claim 77, Brogden teaches that the recommended dosage of ceftriaxone is 1 to 2 g once daily [page 7, third paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have specifically modified the ceftriaxone, as taught by Goodrich, to be administered at a daily dose of 2 g, as taught by Brogden. One would have been motivated to make this modification because Brogden teaches that the recommended dosage of ceftriaxone is 1 to 2 g once daily. MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.” Further, one would have been motivated to administer the ceftriaxone at a daily dose of 2 g because this is a known dosage in the art, and therefore would have a reasonable expectation of success.
Claims 35, 72-76, 79-84 and 86-88 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., 2016 (02/12/2025 PTO-892), Guo et al., 2015 (instant PTO-892), Goodrich et al, 2013 (02/12/2025 PTO-892), Lyseng-Williamson, 2011 (02/12/2025 PTO-892) and Mylan, 2016 (02/12/2025 PTO-892), as applied to claims 35, 72-76, 79-84, and 88 above, and further in view of Le, 2018 (02/12/2025 PTO-892) and Candela et al., 2014 (02/12/2025 PTO-892).
The teachings of Chen, Guo, Goodrich, Lyseng-Williamson, and Mylan are above. Additionally, Lyseng-Williamson teaches that treatment with levetiracetam requires an initial dosage (initiation dose) of levetiracetam followed by increased titration doses at 2 week intervals up to a maximum dose (maintenance dose) and the doses can be given by oral tablet, solution, or intravenous infusion [see page 507, Table V].
However, Chen, Guo, Goodrich, Lyseng-Williamson, and Mylan do not specifically teach that the therapeutic combination is intravenously administered to the subject during the initiation period and that the therapeutic combination is orally administered to the subject during the maintenance period and that the initiation period lasts 1 to 7 days.
Regarding claims 86 and 87, Le teaches that intravenous route of administration is the best way to deliver a precise dose quickly and in a well-controlled manner [page 3, fourth paragraph] and that when given intravenously, a drug is delivered immediately to the bloodstream and tends to take effect more quickly than when given by any other route [page 4, first paragraph].
Candela teaches that switching from intravenous to oral treatment as soon as patients are clinically stable can reduce the costs associated with IV administration and that early switching from IV to oral levetiracetam is possible and leads to a substantial reduction in drug bills [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have intravenously administered the initiation dose, as taught by Lyseng-Williamson. One would have been motivated to administer the initiation dose intravenously because Le teaches that intravenous route of administration is the best way to deliver a precise dose quickly a drug is delivered immediately to the bloodstream and tends to take effect more quickly than when given by any other route and one would want to deliver the drug immediately in order to treat epileptogenesis and prevent the onset of seizures. Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the initiation period only last for 1 to 7 days and then administer the maintenance doses orally. One would have been motivated to have limited the initiation period to 1 to 7 days and then switched to oral maintenance doses because Candela teaches that switching from intravenous to oral treatment as soon as patients are clinically stable can reduce the costs associated with IV administration and that early switching from IV to oral levetiracetam is possible and leads to a substantial reduction in drug bills. Thus, one would want to limit the amount of days of intravenous administration in order to reduce costs. Additionally, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the other therapeutics, i.e. atorvastatin and ceftriaxone, to this specific treatment regimen for convenience and the ease of administration.
New Grounds of Rejection Necessitated by Amendment
Claims 35, 72-74, 78-84, and 88-91 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., 2016 (02/12/2025 PTO-892), Guo et al., 2015 (02/12/2025 PTO-892), and Goodrich et al, 2013 (02/12/2025 PTO-892), as applied to claims 35, 72-74, 79-84, and 88 above, and further in view of Lyseng-Williamson, 2011 (02/12/2025 PTO-892), Mylan, 2016 (02/12/2025 PTO-892), Brogden et al., 2012 (02/12/2025 PTO-892), and Walpole et al., 2018 (instant PTO-892).
The teachings of Chen, Guo, and Goodrich are above.
However, Chen, Guo, and Goodrich do not specifically teach that the levetiracetam, atorvastatin, and ceftriaxone are administered at a low dose.
Regarding claims 89-91, Lyseng-Williamson teaches administering 1000-3000 mg/day of levetiracetam as a therapy to treat the onset of seizures [page 496, left column, fourth paragraph – right column, second paragraph].
Mylan teaches that Lorsat (i.e. atorvastatin) can be administered within the dosage range of 10-80 mg/day as a single daily dose [page 2, sixth paragraph].
Brogden teaches that the recommended dosage of ceftriaxone is 1 to 2 g once daily [page 7, third paragraph].
Walpole teaches that the average body mass globally is 62 kg [see page 3, right column, second paragraph].
Thus, based on the average body mass taught by Walpole, the dosage of levetiracetam taught by Lyseng-Williamson would encompass 16.2 – 48.3 mg/kg/day and the dosage of atorvastatin taught by Mylan would encompass 0.17 – 1.2 mg/kg/day.
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to have modified Lyseng-Williamson, which teaches
administering a dose of 1000-3000 mg/day of levetiracetam, to specifically administer a dose in the range of 16.2-48.3 mg/kg/day, and to have modified Mylan, which teaches administering a dose of 10-80 mg/day of atorvastatin, to specifically administer a dose in the range of 0.16-1.2 mg/kg/day. One would have been motivated to make this modification because Walpole teaches that the average body mass globally is 62 kg, and so, administering a dose of 16.2-48.3 mg/kg/day of levetiracetam and 0.16-1.2 mg/kg/day of atorvastatin to a patient with the average body mass of 62 kg would be a within the ranges of the total doses levetiracetam (i.e. 16.2 mg/kg x 62 kg = 1004 mg and 48.3 mg/kg x 62 kg = 2994 mg) and atorvastatin (0.17 mg/kg x 62 kg = 10.54 mg and 1.2 mg/kg x 62 kg = 74.4 mg) that Lyseng-Williamson and Mylan teach are acceptable doses, respectively. It further would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the ceftriaxone at a dose of 2 g/day, as taught by Brogden. One would have been motivated to administer the ceftriaxone at this dosage because Brogden teaches that this is an acceptable dosage for the ceftriaxone. MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.” Further, one would have been motivated to administer each of the therapeutics at these doses because they are known dosages in the art for each therapeutic, and therefore would have a reasonable expectation of success.
Further, regarding claim 78, it would have been obvious to have picked any dose within the known ranges for each of the levetiracetam, atorvastatin, and ceftriaxone because they are known dosage ranges for each of the therapeutics. Specifically, it would be obvious to choose 50 mg of atorvastatin, 1000 mg of levetiracetam, and 1000 mg (i.e. 1 g) of ceftriaxone, thereby arriving at a ratio of atorvastatin to levetiracetam to ceftriaxone of 1:20:20, because Lyseng-Williamson, Mylan, and Brogden teach that these are known acceptable doses for each of the therapeutics. MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.” Further, one would have been motivated to administer each of the therapeutics at these doses because they are known dosages in the art for each therapeutic, and therefore would have a reasonable expectation of success.
Response to Arguments
The rejections under 35 U.S.C. 103 over Chen, Guo, and Goodrich are maintained. On page 7 of the remarks, Applicant argues that Chen’s TBI model is flawed because the introduction of kainic acid comprises the model’s validity because Chen merely suggests that levetiracetam treats kainic acid-induced seizures following TBI, and that one would not have considered the findings of Chen to be probative of levetiracetam’s effectiveness for treating epileptogenesis following a brain insult. This is not found persuasive because the kainic acid-induced status epilepticus (KASE) rat model, which is used by Chen, is a widely used, well-validated model to study epilepsy [see Bertoglio et al, 2017; instant PTO-892]. Thus, Chen is in the same field of endeavor as the instantly claimed method, and one of ordinary skill in the art would not dismiss the model of Chen. Further, Chen uses the same animal model as that taught in the instant specification (i.e. FPI) and so it is unclear how this model would not speak to the instantly claimed invention. Applicant further argues that even if Chen’s model was a valid TBI model, Chen only discloses that levetiracetam reduces seizure severity and ictal duration in the short-term and did not tailor the study to probe levetiracetam's effectiveness in treating epileptogenesis as opposed to early-onset acute seizures after an insult. This is not found persuasive because this is a misrepresentation of the teachings of Chen. Chen clearly distinguishes between two treatment groups: FPI early onset seizures (FPI-ES) to mimic early post injury seizures and late onset seizures (FPI-LS) to mimic late post-injury seizures [see page 582, left column, second paragraph] with seizures induced at 2, 3, and 4 weeks after FPI [see page 582, right column, first paragraph], and that levetiracetam infusion can ameliorate neuron degradation after FPI and KA induced seizures, which is related to the susceptibility and severity of the post traumatic seizures [see page 587, right column, first paragraph]. Further, Chen teaches that levetiracetam has antiepileptic effects that may involve several mechanisms related to ameliorating epileptogenesis [page 588, left column, seventh paragraph]. Thus, Chen clearly indicates that levetiracetam is an effective treatment for epileptogenesis. Prior art is art for all that it teaches. See MPEP 2121.01.
Further on pages 6-7 of the remarks, Applicant argues that Chen makes no mention of combining levetiracetam with any additional therapeutic agents and nothing in Chen would have suggested that the combination of levetiracetam, ceftriaxone, and atorvastatin would be a safe and effective therapy for treating epileptogenesis in a human after a brain insult, and thus, one would not have been motivated to have combined the levetiracetam with ceftriaxone and atorvastatin with a reasonable expectation of success. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The Examiner clearly articulated why it would have been obvious to combine the teachings of Chen, Guo, and Goodrich to arrive at the claimed combination of levetiracetam, ceftriaxone, and atorvastatin for treating epileptogenesis in a human after a brain insult. See rejection above. On page 7 of the remarks, Applicant argues that Guo only teaches that atorvastatin merely reduces the risk of poststroke early onset seizures and does not significantly reduce the risk of poststroke epilepsy (PSE). This is again a misrepresentation of what the art teaches. Just because Applicant has chosen to label the results of the atorvastatin treatment on PSE of Guo as insignificant, does not indicate that the treatment is not effective. To the contrary, Guo clearly teaches that statin use can reduce the risk of PSE in patients who presented with ES [page 704, left column] and that statin use was associated with reduced risk of poststroke epilepsy [see Abstract]. Applicant further argues that Guo makes no mention of combining atorvastatin with any additional therapeutic agents and nothing in Guo would have suggested that the combination of levetiracetam, ceftriaxone, and atorvastatin would be a safe and effective therapy for treating epileptogenesis in a human after a brain insult, and thus, one would not have been motivated to have combined the atorvastatin with levetiracetam and atorvastatin with a reasonable expectation of success. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The Examiner clearly articulated why it would have been obvious to combine the teachings of Chen, Guo, and Goodrich to arrive at the claimed combination of levetiracetam, ceftriaxone, and atorvastatin for treating epileptogenesis in a human after a brain insult. See rejection above.
On pages 7-8 of the remarks, Applicant argues that while Goodrich teaches that treatment with ceftriaxone after TBI reduced seizure frequency and duration, one would not have been motivated to administer ceftriaxone to treat epileptogenesis in a human after a brain insult because ceftriaxone, and other cephalosporins, have been reported to induce seizures in some patients, citing the reference of Kim for support. This is not found persuasive because Kim teaches that neurologic adverse effects of ceftriaxone are infrequent [see page 1, left column, first paragraph] with only seven cases of ceftriaxone-induced neurotoxicity reported to date, with only two of the seven being NCSE [see page 1122, right column, second paragraph]. Thus, the art still clearly teaches that this is an effective treatment and there is no evidence that the person of ordinary skill in the art would have considered this infrequent risk sufficient to avoid treatment with ceftriaxone. Applicant further argues that Goodrich makes no mention of combining ceftriaxone with any additional therapeutic agents and nothing in Goodrich would have suggested that the combination of levetiracetam, ceftriaxone, and atorvastatin would be a safe and effective therapy for treating epileptogenesis in a human after a brain insult, and thus, one would not have been motivated to have combined the ceftriaxone with levetiracetam and atorvastatin with a reasonable expectation of success. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The Examiner clearly articulated why it would have been obvious to combine the teachings of Chen, Guo, and Goodrich to arrive at the claimed combination of levetiracetam, ceftriaxone, and atorvastatin for treating epileptogenesis in a human after a brain insult. See rejection above.
Further on page 8 of the remarks, Applicant argues that the claimed method produces unexpected results, first citing the reference of Hameed for support. The results of Hameed to support unexpected results are not found persuasive because the results of Hameed do not demonstrate the results of the levetiracetam, atorvastatin, or ceftriaxone alone. Therefore, the Examiner cannot make a determination of a trend that would lead to a conclusion of unexpected results. The burden is on Applicant to provide to the Examiner a trend proving the unexpected results. See MPEP 716.02(b). Additionally, Applicant cites the reference of Welzel for support of unexpected results. The results of Welzel are also not found persuasive because while Welzel teaches that the combination of levetiracetam, atorvastatin, and ceftriaxone provided a remarkable neuroprotective effect and that the levetiracetam alone exerted no effect, the results of Welzel do not demonstrate the results of atorvastatin, or ceftriaxone alone. Therefore the Examiner cannot make a determination of a trend that would lead to a conclusion of unexpected results. The burden is on Applicant to provide to the Examiner a trend proving the unexpected results. See MPEP 716.02(b). In view of the above, Applicant’s arguments of unexpected results are not persuasive to rebut the 103 rejection. On pages 11-12, Applicant summarizes their arguments which have been addressed above and will not be reiterated and are incorporated herein.
On pages 12-13, Applicant argues the rejections of the remaining dependent claims under 35 U.S.C. 103 and that the additional references applied do not remedy the deficiencies of Chen, Guo, and Goodrich. These arguments are not found persuasive because no such deficiency exists. See above.
Conclusion
No claims are allowed.
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.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675