DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a continuation of and claims priority to U.S. Patent Application No. 17/477,248, filed 16 September 2021, which is a divisional of and claims priority to U.S. Patent Application No. 16/806,594, filed 2 March 2020, which is a continuation application of and claims priority to U.S. Patent Application No. 14/955,922, filed 1 December 2015, which is a continuation application of and claims priority to U.S. Patent Application No. 14/003,780, filed 9 October 2013, which is a 35 U.S.C. § 371 national phase application of International Application No. PCT/GB2012/000229, filed 9 March 2012, which claims the benefit of U.S. Provisional Applications Nos. 61/464,776, filed 9 March 2011, 61/464,809, filed 9 March 2011, and 61/628,339, filed 28 October 2011.
Claim Status
Claims 22-27, 29-34, and 36-39 remain pending and under examination. Claims 1-21, 28, and 35 remain canceled by Applicants. Acknowledgement is made of the receipt and entry of the amendment to the claims filed on August 13, 2025.
Action Summary
Claims 22-27, 29-34, and 36-39 rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Wang, Journal of Biological Chemistry, Volume 282, Number 39, September 2007, pages 28408-28418 in view of Matteo, Cardiovasc Ther. 2010 Oct; 28(5): e72–e91, Ortega (US5,049,586), and Banerjea, Neuropediatrics (Stuttgart, Germany) (2002), 33(4), 215-220, are maintained.
Claims 22-27, 29-34, and 36-39 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,111,845, are maintained.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 22-27, 29-34, and 36-39 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Wang, Journal of Biological Chemistry, Volume 282, Number 39, September 2007, pages 28408-28418 in view of Matteo, Cardiovasc Ther. 2010 Oct; 28(5): e72–e91, Ortega (US5,049,586), and Banerjea, Neuropediatrics (Stuttgart, Germany) (2002), 33(4), 215-220. Wang is previously cited in the parent case # 14/955,922.
Wang teaches HDAC inhibitors were found to inhibit the expression of pro-inflammatory cytokines and mediators in some inflammatory modes; for example, SAHA attenuates the expression of certain NF-Kappa betta-regulated cytokines including TNF-α, IL-1β, IL-6, and IFN-ϒ in a mousse model. (See page 28408, second col, last paragraph.) Moreover, Wang teaches HDAC inhibitors such as TSA and butyrate increase the expression of tissue-type plasminogen activator, a key activator of fibrinolysis in HUVEC and human peritoneal mesothelial cells; thus, HDAC inhibitors by simultaneously decreasing agonist-induced expression of human tissue factor (TF) in vessels and monocytes as well as increasing endothelial tissue-type plasminogen activator expression, might have utility as a therapy for thrombosis. (See page 28417, first column, second paragraph.) Wang also teaches valproic acid, TSA, MS-275, and sodium butyrate all inhibit TNF-α, and LPS-driven tissue factor activity. (See Table 1.) Wang teaches TF activity and protein level induction in human umbilical vein endothelial cells stimulated by the physiologic agonist’s tumor necrosis factor alpha, IL-1β, and lipopolysaccharide; the TF activity is inhibited by valproic acid, TSA and sodium butyrate and histone acetylase inhibitors may be a novel therapy for thrombosis disorder. (See Abstract.) Furthermore, Wang teaches HDACi, by simultaneously decreasing agonist-induced expression of TF in vessels and monocytes as well as increasing endothelial tissue-type plasminogen activator expression, might have utility as a therapy for deep venous thrombosis. (See page 28417, left column, second paragraph.)
Wang does not teach valproic acid or a pharmaceutically acceptable salt thereof in the amount of about 50 mg to 1000 mg.
Matteo teaches one of the most studied biomarkers of the fibrinolysis system is the plasminogen activator inhibitor-1 (PAI-1). Interestingly, its expression is not only elevated in the elderly, but also significantly enhanced in a variety of clinical conditions that are typical of the aging process (e.g., obesity, insulin resistance, psychosocial stress, decreased immune responses, increased inflammation, vascular sclerosis/remodeling). (See page 2, fourth paragraph.) Moreover, Matteo teaches Hypofibrinolysis due to high PAI-1 concentrations is also commonly found in patients with high thrombotic risk, such as obesity and metabolic syndrome, pregnancy, and in certain obstetric complications (e.g., preeclampsia). (See page 11, fifth paragraph.) Matteo further teaches the impairment of the fibrinolytic cascade (and the increase of PAI-1 concentrations) is easily associable with a wide range of thrombotic conditions, including myocardial infarction, stroke, peripheral artery disease, deep vein thrombosis, and disseminated intravascular coagulation. (See page 10, fourth paragraph.)
Ortega teaches
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. (See lines tables of column 4 bridging tables of column 5.) The 500 mg tablet of valproic acid at 25.00 hours with a blood concentration 16.44 give a value 0.113 nM (16.44 µg/ml x FW of valproic acid of 144.211)/1000). The Cmax value for the 500 mg tablet of valproic acid which is 68.94 µg/ml (68.94 µg/ml x 144.211)/1000 gives 0.53 nM. The 25.00-hour time for the 16.44 µg/ml can read on daily.
Banerjea teaches sodium valproate was able to reduce fibrinogen, procoagulatory and anticoagulatory factors. (See Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use valproic acid 500 mg to treat deep vein thrombosis by reducing or normalizing endogenous fibrinolysis capacity in a subject that has increased fibrin deposition and/or reduced fibrinolytic capacity to give Applicant’s claimed invention. One would have been motivated to do so because Wang teaches HDAC inhibitors can have utility as a therapy for deep vein thrombosis by decreasing agonist-induced human tissue factor expression that is partly governed by NF-κB-related TF-κB, and lipopolysaccharide and because Ortega teaches sodium valproate in the amount 500 mg/day is an effective table formulation that produces a blood concentration of valproic acid in the amount of 0.1 nM and a Cmax value of 0.53 nM along with the fact that Banerjea teaches sodium valproate was able to reduce fibrinogen, procoagulatory and anticoagulatory factors, also because Matteo teaches the impairment of the fibrinolytic cascade (and the increase of PAI-1 concentrations) is easily associable with a wide range of thrombotic conditions, including myocardial infarction, stroke, peripheral artery disease, deep vein thrombosis. One would reasonably expect sodium valproate or valproic acid in the amount of 500 mg to successfully reduce the risk of a pathological condition in a subject caused wholly or at least in part by increased fibrin deposition and/or reduced fibrinolytic capacity and successfully treat deep vein thrombosis by reducing or normalizing endogenous fibrinolysis capacity in order to produce a blood concentration of valproic acid in the amount of 0.1 nM and a Cmax value of 0.53 nM.
Acknowledgment of Applicant’s remark dated 08/13/2025 is made.
Applicant’s argument:
Applicant argues Wang and Matteo fail to teach the recited dose of valproic acid. Wang indicates that VPA is a known member of a large group of known HDAC inhibitors and provides evidence of an effect of VPA on TNF-a- and LPS-driven tissue factor activity induction in vitro. (Wang, abstract and Table 1). Wang does not describe the use of any HDAC inhibitor in an amount about 50 mg to about 1000 mg per day to a subject having increased fibrin deposition and/or reduced fibrinolytic capacity as claimed. Matteo is cited for teaching that one of the most studied biomarkers of the fibrinolysis system is the plasminogen activator inhibitor-1 (PAI-1) and hypofibrinolysis due to high PAI-1 concentrations is commonly found in patients with high thrombotic risk. (Office Action, page 6). Matteo is silent to the administration of VPA or a pharmaceutically acceptable salt thereof, in particular, an amount of about 50 mg to about 1000 mg per day to a subject having increased fibrin deposition and/or reduced fibrinolytic capacity. As such, it is clear from the whole of Ortega and Banerjea that these references are directed to the use of VPA for treating epilepsy. The use of the compositions of Ortega and Banerjea is, thus, different from that which is claimed.
Examiner’s response:
In response, Applicant’s argument is not persuasive. It may well be true that the combination of Wang and Matteo, when taken together, fail to teach or suggest the administration of VPA or a pharmaceutically acceptable salt thereof, in an amount of about 50 mg to about 1000 mg per day. However, Ortega teaches sodium valproate in the amount 500 mg/day is an effective table formulation that produces a blood concentration of valproic acid in the amount of 0.1 nM and a Cmax value of 0.53 nM. Even though, Ortega teaches on the background valproic acid or its salts have known utility as anticonvulsant, Ortega teaches the tablet or capsule formulation sodium valproate formulation in the amount in the amount 500 mg/day without specifying or mentioning the use for formulation. A person of ordinary skill in the art would at least start with the known therapeutic dose range of sodium valproate taught by Ortega when using the method taught by the combination of Wang and Matteo having different, or "off-label," condition such as deep vein thrombosis because of the fact that both the anticonvulsant property mentioned by Ortega and the thrombosis property taught by Wang are linked by the inhibition of HDAC. The Examiner provides Hu et al (BMC Neurosci (2016) 17:22) solely to rebut Applicant’s argument that Ortega does not teach or suggest that the dosage form (tablet) or dose administered therein treats any disease or condition. Hu teaches
Histone deacetylase inhibitor SAHA can suppress seizure-induced TLR4/MYD88 signaling and inhibit TLR4 gene expression through histone acetylation regulation. This suggests that SAHA may protect against seizure induced brain damage. (See Abstract.) A POSA can reasonably expect HDAC to successful be inhibited with the amount taught by Ortega because both the anticonvulsant activity taught by Ortega and the deep vein thrombosis taught by Wang together with Matteo are linked by the physiological similarities of HDAC, i.e., HDAC inhibition. Lastly, Banerjea was cited to show that VPA was able to reduce fibrinogen, pro-coagulatory and anticoagulatory factors where fibrinogen Again, Wang teaches HDAC inhibitors such as TSA and butyrate increase the expression of tissue-type plasminogen activator, a key activator of fibrinolysis in HUVEC and human peritoneal mesothelial cells; thus, HDAC inhibitors by simultaneously decreasing agonist-induced expression of human tissue factor (TF) in vessels and monocytes as well as increasing endothelial tissue-type plasminogen activator expression, might have utility as a therapy for thrombosis. (See page 28417, first column, second paragraph.) Matteo teaches one of the most studied biomarkers of the fibrinolysis system is the plasminogen activator inhibitor-1 (PAI-1). Moreover, Matteo teaches Hypofibrinolysis due to high PAI-1 concentrations is also commonly found in patients with high thrombotic risk, such as obesity and metabolic syndrome, pregnancy, and in certain obstetric complications (e.g., preeclampsia). (See page 11, fifth paragraph.) In sum, deep vein thrombosis can be treated via two separate mechanisms: (1) inhibition of Histone Deacetylases (HDACs) increases the production of tissue plasminogen activator (tPA) is a protein that breaks down blood clots by activating plasminogen into plasmin, which then degrades fibrin that forms clots, a process called fibrinolysis, restoring blood flow; (2) inhibition of Histone Deacetylases (HDACs) affects the conversion of fibrinogen to fibrin indirectly through several cellular and regulatory pathways, rather than by acting directly on the conversion process itself. The conversion is primarily a direct enzymatic process catalyzed by the protease thrombin.
Applicant’s argument:
Applicant argues "Banerjea teaches sodium valproate was able to reduce fibrinogen, procoagulatory and anticoagulatory factors" [emphasis added] (Office Action, page 9, first paragraph) is of no relevance to the claimed methods as Banerjea relates to the process of clot formation while the present invention relates to fibrinolysis, i.e., clot breakdown. Nowhere does Banerjea teach, suggest, or provide any guidance for using VPA to reduce fibrinolysis.
Examiner’s response:
In response, Applicant’s argument is not persuasive. It may well be true that Banerjea relates to the process of clot formation while the present invention relates to fibrinolysis, i.e., clot breakdown. However, the claim requires treating a pathological condition associated with excess fibrin deposition and/or thrombus formation. Fibrinogen is indirectly associated with fibrinolysis primarily through its conversion into fibrin, which forms the physical structure of a blood clot. The concentration, structure, and quality of this resulting fibrin mesh largely determine how easily the clot can be broken down by the fibrinolytic system. Anticoagulation factors are indirectly related to fibrinolysis through a tightly regulated system that balances clot formation (coagulation) and clot breakdown (fibrinolysis). Therefore, the teaching of Banerjea can reasonably be considered to be indirectly related to fibrinolysis. One of ordinary skill in the art would expect the decrease of fibrinogen, procoagulatory or anticoagulatory factors to have an indirect effect on fibrinolysis.
Applicant’s argument:
Applicant argues that Figure 4 of the application as filed (represented below for the Examiner's convenience), which illustrates not only the unexpected discovery that VPA has a potent effect on t-PA levels in the presence of the fibrinolysis inhibitor TNF-a, but also that this effect increases in a non-linear manner such that potent effects are obtained without a significant increase in dose. This unexpected mode of action and non- linear dosage response allows VPA to deliver a local and time-limited effect at very low doses, rendering it particularly useful in long term treatment and as a prophylactic agent against inflammatory suppression of fibrinolysis.
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Examiner’s response
In response, Applicant’s argument is not persuasive. The Examiner does not dispute the fact that VPA has a potent effect on t-PA levels in the presence of the fibrinolysis inhibitor TNF-α, but also that this effect increases in a non-linear manner such that potent effects are obtained without a significant increase in dose. However, the Examiner contends that TNF-α is not in the claim. The claim only requires the administration of valproic acid, or a pharmaceutically acceptable salt thereof in an amount from about 50 mg to about 1000 mg per day in a subject that has increased fibrin deposition and/or reduced fibrinolytic capacity for treating deep vein thrombosis, which is obvious over the collective teaching of Wang, Matteo, Ortega, and Banerjea. Moreover, Wang teaches HDAC inhibitors were found to inhibit the expression of pro-inflammatory cytokines and mediators in some inflammatory modes; for example, SAHA attenuates the expression of certain NF-Kappa betta-regulated cytokines including TNF-α, IL-1β, IL-6, and IFN-ϒ in a mousse model. (See page 28408, second col, last paragraph.) Moreover, Wang teaches HDAC inhibitors such as TSA and butyrate increase the expression of tissue-type plasminogen activator, a key activator of fibrinolysis in HUVEC and human peritoneal mesothelial cells; thus, HDAC inhibitors by simultaneously decreasing agonist-induced expression of human tissue factor (TF) in vessels and monocytes as well as increasing endothelial tissue-type plasminogen activator expression, might have utility as a therapy for thrombosis. (See page 28417, first column, second paragraph.) Wang also teaches valproic acid, TSA, MS-275, and sodium butyrate all inhibit TNF-α, and LPS-driven tissue factor activity. (See Table 1.) As such, one of ordinary skill in the art would expect the sodium valproate to reduce TNF-α by inhibition of HDAC with the 500 mg dose taught by Ortega.
Applicant argument:
Applicant argues the data presented in the specification shows that VPA can directly provide a significant fibrinolytic effect, and provides the first disclosure that this effect is able to restore fibrinolytic activity by counteracting inflammation-induced inhibition of fibrinolysis through suppression of t-PA. This finding allows for VPA to provide an effective treatment for diseases and disorders related to impaired fibrinolysis, and excess fibrin deposition and/or thrombus formation. Indeed, in the absence of the knowledge that VPA is able to deliver an effect through the locally acting and time-limited t-PA pathway, one of ordinary skill in the art would have no reason to consider further investigating the use of VPA as an effective treatment or prophylactic for disorders related to impaired fibrinolysis, and excess fibrin deposition and/or thrombus formation.
Examiner’s response:
In response, Applicant’s argument is not persuasive. It may well be true that the data presented in the specification shows that VPA can directly provide a significant fibrinolytic effect, and provides the first disclosure that this effect is able to restore fibrinolytic activity by counteracting inflammation-induced inhibition of fibrinolysis through suppression of t-PA and this finding allows for VPA to provide an effective treatment for diseases and disorders related to impaired fibrinolysis, and excess fibrin deposition and/or thrombus formation. However, the data is not commensurate in scope with the claimed invention. Specifically, the data showing low dose 0.05-0.3 mM having lower side effects to counteract inflammation-induced suppression to t-PA, which in turns increases fibrinolytic effects thereby targeting clot formation. The 0.05-0.3 mM dose is not in the claim. Moreover, said dose was used in the in vitro assay of Figure 4. The claimed method is interpreted by the Examiner to be an in vivo method due to the administration step. There is nothing in the specification that demonstrates the 0.05-0.3 mM can be extrapolated to include the claimed about 50 mg to about 1000 mg. In fact, the claim broadly recites any subject population, any pathological condition directly/indirectly associated with excess fibrin deposition and/or thrombus formation, any route of administration, and about 50 mg to about 1000 mg dose per day. Therefore, the data presented in Fig. 4 is not commensurate is scope with the claim. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Furthermore, Wang teaches TSA and four other HDACi (apicidin, MS-275, sodium butyrate, and valproic acid) all inhibit by ~90% TF activity and protein level induction in human umbilical vein endothelial cells stimulated by the physiologic agonists tumor necrosis factor (TNF)-, interleukin-1, lipopolysaccharide, and HOSCN without affecting expression of the NF-ϏB-regulated adhesion molecules ICAM-1 and E-selectin, but also Wang conclude that histone deacetylases, particularly HDAC3, play a hitherto unsuspected role in regulating TF expression and raise the possibility that HDACi might be a novel therapy for thrombotic disorders. (See Abstract.) Wang appears focus on HDAC3 inhibitors and not all HDAC inhibitors. Second, the HDAC inhibitors of Wang only relate to the inhibition of tissue factors and not regulation of all endothelial cell gene expression. Moreover, Ortega teaches sodium valproate in the amount 500 mg/day is an effective table formulation that produces a blood concentration of valproic acid in the amount of 0.1 nM and a Cmax value of 0.53 nM. Banerjea teaches sodium valproate was able to reduce fibrinogen, procoagulatory and anticoagulatory factors. (See Abstract.) Matteo teaches the impairment of the fibrinolytic cascade (and the increase of PAI-1 concentrations) is easily associable with a wide range of thrombotic conditions, including myocardial infarction, stroke, peripheral artery disease, deep vein thrombosis, and disseminated intravascular coagulation. Therefore, guided by the collective teachings of Wang, Matteo, Ortega, and Banerjea, one would reasonably expect VPA to be effective for treating Deep vein thrombosis by improving or normalizing endogenous fibrinolysis impaired by local or systemic inflammation successfully.
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 22-27, 29-34, and 36-39 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,111,845. Although the claims at issue are not identical, they are not patentably distinct from each other because.
The U.S. patent claims teach a method of treating or reducing the risk of a pathological condition associated with excess fibrin deposition and/or thrombus formation in a subject in need thereof, comprising administering to the subject at least one dose of a therapeutically effective amount of valproic acid, or a pharmaceutically acceptable salt thereof, wherein the maximum plasma concentration (Cmax) of the valproic acid, or salt and/or metabolite thereof in the subject after administration occurs during a time period that is from four hours before to one hour after the Cmax of PAI-1 in the subject. (See claim 1.) The at least one dose of valproic acid, or the pharmaceutically acceptable salt thereof; is from about 50 to about 1000 mg. (See claim 4.) Moreover, The U.S. patent claims teach the pathological condition associated with excess fibrin deposition and/or thrombus formation is selected from the group consisting of atherosclerosis, myocardial infarction, ischemic stroke, deep vein thrombosis, superficial vein thrombosis, thrombophlebitis, pulmonary embolism, disseminated intravascular coagulation, renal vascular disease and intermittent claudication. (See claims 10 and 11.)
Accordingly, since the U.S, patent claims teach the same amount of valproic acid claimed and the same compound (valproic acid) claimed, the recited plasma concentration and the Cmax claimed are necessarily present absent evidence to the contrary. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed method is different from that taught by the prior art and to establish patentable differences. See in re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Therefore, the U.S. patent claims anticipate the instant claims.
Applicant argues that Applicant will consider filing a terminal disclaimer once allowable subject matter is indicated.
In response, since the claims are note allowable, a terminal disclaimer will be needed.
Conclusion
No claims are allowed.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628