DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application, filed on 01/06/2021, claims priority from U.S. Provisional Applications No. 62/698,558 filed on 07/16/2018 and PCT/MY2019/000025 filed on 07/16/2019.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/07/2026 has been entered.
DETAILED ACTION
The Applicant’s Amendment and Arguments submitted on 05/01/2026 have been received and have been carefully considered.
Claims 16 was amended, and claims 1-15, 17-18, and 21, were previously cancelled. Claims 16, 19-20 and 22-30 are pending.
Rejection Maintained/Modified/Added1 in view of the Amendment
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.
Claims 16, 19-20, and 22-30 remain rejected under 35 U.S.C. 103 as being unpatentable over U. Heresco-Levy (WO 2014/191992A1, 12/04/2014, “Heresco-Levy” cited on the previous PTO-892 dated 08/23/2023) in view of H. Lane et al. (JAMA Psychiatry. 2013; 70(12):1267-1275, “Lane” cited in the previous PTO-892 dated 08/23/2023), Y. Wang et al. (J. Neuroimmunol. 2017 Nov 15; 312:59-65, “Wang” cited in the PTO-892 dated 08/01/2024), H. Guan et al. (Neuroimmunology and Neuroinflammation, 2016 3. 189, “Guan” cited in the previous PYO-892 dated 08/23/2023), B. Dengler, et al. Clinical Neurology and Neurosurgery, Volume 160, 2017, Pages 38-39, ISSN 0303-8467, “Dengler” cited in the PTO-892) and P. Kuppuswamy, et al. General Hospital Psychiatry, Volume 36, Issue 4, 2014, Pages 388-391, “Kuppuswamy” cited in the PTO-892).
Applicants’ claimed invention is directed to a method for treating anti-N-methyl-D-aspartate receptor (anti- NMDAR) encephalitis in a subject in need thereof, comprising administering to the subject an effective amount of a benzoic acid salt in combination with an immune therapy with intravenous immunoglobulin, wherein the subject is refractory to immune therapy, plasmapheresis, and/or pulse therapy with a steroid, and wherein the benzoic acid salt is sodium benzoate.
With respect to claim 16, Heresco-Levy teaches a method of mitigating the severity of lowering the incidence of NMDAR antibody production and treating a disease associated with NMDAR antibody production, comprising administering a NMDAR agonist, D-amino acid oxidase inhibitor, wherein the disease associated with NMDAR antibody is anti-NMDAR encephalitis, [Pg. 7, [0026-0027], claim 5], wherein the D-amino acid oxidase inhibitor is benzoic acid, [Claim 14], and wherein the method further comprises combination with immunotherapy [Pg. 10, [0039]]. Heresco-Levy teaches that the D-amino acid oxidase inhibitor, benzoic acid is administered at a dosage of 500-2000 mg/day, [Claim 14]. Heresco-Levy teaches that the patients selected for the studies have treatment-resistance to pharmacotherapy with presently available antipsychotic drugs. [Pg. 13, [0060]]. Heresco-Levy also teaches an example wherein a patient is refractory to treatment with various classes of antipsychotic drugs. [Pg. 14, [0064]].
Heresco-Levy teaches that immunotherapy is the most important component in the treatment of anti-NMDAR encephalitis, wherein 5 -days course of concurrent IVIG (intravenous immunoglobulin) and methylprednisolone should be given, and if clear improvement is seen within 10 days, supportive care should be continued. [Pg. 4, [0014]].
While Heresco-Levy teaches the use of benzoic acid in an amount of 200-2000 mg/day for treating anti-NMDAR encephalitis and that Heresco-Levy’s IVIG refers to intravenous immunoglobulin as evidenced by Wang, Heresco-Levy does not specifically teach benzoic acid salt, sodium benzoate in combination of immunoglobulin immunotherapy. Also, while Heresco-Levy teaches that the patients are refractory to available therapy, Heresco-Levy does not specifically teach refractory to the therapy recited in amended claim 1.
However, this deficiency is cured by Lane, Wang, Guan, Dengler and Kuppuswamy.
In the same field of endeavor, Lane teaches a method of using D-amino acid oxidase inhibitor, sodium benzoate for enhancing NMDAR-mediated neurotransmission and treating disorder mediated by hypofunction of the N-methyl-D-aspartate receptor, wherein patients with schizophrenia treated with antipsychotic medications were treated with 1000 mg/day of sodium benzoate for six weeks. Lane teaches that sodium benzoate enhances NMDAR function, produced significant improvement of symptoms and neurocognition in patients and its well tolerated without significant adverse effects. [Lane, Abstract].
In the same field of endeavor, Wang teaches treatment for anti-NMDAR encephalitis in children, who are patients, wherein the patients received first-line immunotherapy and a second-line immunotherapy and more than 86% of the patients achieved good outcomes, wherein the first-line immunotherapy is intravenous methylprednisolone and intravenous immunoglobulin (IVIG, 0.4 g/kg per day for 5 days). [Wang, Abstract, pg. 61, col. 2, 2nd para., and Table 3]. Wang teaches that the subjects are refractory to first line therapy, combination treatment of intravenous methylprednisolone, intravenous immunoglobulin “subject was treated with methylprednisolone and intravenous immunoglobulin, but had no response to this first-line therapy” [pg. 61, col. 2, last para. and pg. 62, col. 2, last para.]. Instant specification describes pulse therapy with a steroid as pulse therapy with methylprednisolone, [instant specification, page 4, line 9-10].
In the same field of endeavor, Guan teaches administration of N-methyl-D-aspartate (NMDA)-agonist, to a patient with anti-NMDAR encephalitis refractory to immunotherapy, wherein administration of NMDA-agonist improved patient’s symptoms gradually and significantly. [Abstract]. Guan teachings and case report proved that NMDA-agonists can be great option for anti-NMDAR encephalitis refractory to immunotherapy. [Guan entire document].
With regard to claim 1 amendment that the subject is refractory to immune therapy, plasmapheresis and pulse therapy with a steroid, Kuppuswamy teaches that corticosteroids, plasma exchange, and intravenous immunoglobulin are first-line immunotherapy and Anti-NMDA receptor encephalitis patients not responding the first-line therapy are required a second-line therapy and a third-line therapy is also required for non-responders, [Abstract], and Dengler teaches that most of Anti-NMDA receptor encephalitis are refractory to immunotherapy with steroids, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (PLEX) and more than 57% of the patients required second-line and third-line therapy. [pg. 38, col. 1, 1st para].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine the teachings of the cited references and substitute Heresco-Levy’s D-amino acid oxidase inhibitor, benzoic acid, with other D-amino acid oxidase inhibitors, such as 1000 mg/day sodium benzoate, taught by Lane in treating anti-NMDAR encephalitis in a subject refractory to immune therapy as taught by Guan. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Heresco-Levy teaches D-amino acid oxidase inhibitor, benzoic acid for treating anti-NMDAR encephalitis and Lane teaches a method of using D-amino acid oxidase inhibitor, sodium benzoate for treating disorder mediated by hypofunction of the N-methyl-D-aspartate receptor and teaches that sodium benzoate enhances NMDAR function and NMDAR-mediated neurotransmission, produced significant improvement in patients, and its well tolerated without significant adverse effects.
One of ordinary skill in the art would have been motivated with reasonable expectation of success to combine sodium benzoate with immunoglobulin in treating anti-NMDAR encephalitis because Heresco-Levy teaches that intravenous immunoglobulin immunotherapy is the most important components in the treatment of anti-NMDAR encephalitis, and Wang teaches treating patients with anti-NMDAR encephalitis with immunoglobulin immunotherapy as a first-line therapy achieved good outcomes. Moreover, immunoglobulin as taught by Heresco-Levy and Wang is the first-line therapy for anti-NMDAR encephalitis, and benzoate is taught by Heresco-Levy and Lane for treating the very same condition, anti-NMDAR encephalitis, "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, 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).
One of ordinary skill in the art would have been motivated to administer sodium benzoate in combination with intravenous immunoglobulin for treat anti-NMDAR encephalitis in a subject refractory to immune therapy, plasmapheresis and pulse therapy with a steroid because Heresco-Levy teaches that the NMDAR agonist treat subject refractory to pharmacotherapy with presently available antipsychotic drugs and various classes of antipsychotic drugs; Guan teaches that administration of NMDA-agonist, to a patient with anti-NMDAR encephalitis refractory to immunotherapy improved patient’s symptoms gradually and significantly; Wang teaches that anti-NMDAR encephalitis patients are refractory to first line therapy, combination treatment of intravenous methylprednisolone, intravenous immunoglobulin [pg. 61, col. 2, last para. and pg. 62, col. 2, last para.]; Kuppuswamy teaches that second-line and a third-line therapies are required for anti-NMDAR encephalitis patients refractory to corticosteroids, plasma exchange, and intravenous immunoglobulin and for non-responders, [Abstract], and Dengler teaches that most of anti-NMDAR encephalitis are refractory to immunotherapy with steroids, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (PLEX) and more than 57% of the patients required second-line and third-line therapy. [pg. 38, col. 1, 1st para]. Therefore, refractory to immune therapy, plasmapheresis and pulse therapy with a steroid in patients with anti-NMDAR encephalitis is well known in the art, and it would have been prima facie obvious to one of ordinary skill in the art to administer the sodium benzoate and intravenous immunoglobulin as a second-line therapy.
Therefore, one of ordinary skill in the art would have been motivated to substitute Heresco-Levy’s D-amino acid oxidase inhibitor with Lane’s D-amino acid oxidase inhibitor, sodium benzoate, and combine sodium benzoate with immunoglobulin immunotherapy for treatment of anti-NMDAR encephalitis refractory to immune therapy, plasmapheresis and pulse therapy with a steroid, to arrive at each and every structural/method limitation of claim 16. Claim 16 recitation of:
“… wherein a psychotic symptom is reduced, wherein the psychotic symptom comprises dissociation, agitation or a combination thereof …”,
are inherently met by the administration of 1000 mg/day sodium benzoate to subjects because they necessarily flow from the administration. MPEP § 2112. Furthermore, claim scope is not limited by claim language that does not limit a claim to a particular structure. MPEP § 2111.04 (citing In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005) (whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited). The above claim 16 limitations do not limit the method steps in any fashion, but merely reflect the intended result of the claimed administration.
Moreover, the combination of Heresco-Levy, Lane, Wang, and Guan teach a method for treating anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in a subject in need thereof by administering sodium benzoate. the combination of Heresco-Levy, Lane, Wang, and Guan are silent on the positive effects of sodium benzoate administration of reducing dissociation and agitation but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting psychotic symptom is inherently reduced. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
With regard to claim 19, Heresco-Levy teaches that the antibodies of patients with anti-NMDAR encephalitis decrease the surface density and synaptic localization of NMDAR clusters via antibody mediated capping and internalization, [Pg. 3, [0011]].
With regard to claim 20, Heresco-Levy teaches that the method enhances NMDAR-mediated neurotransmission for encephalitis associated with antibodies against NMDAR, [Pg. 5, [0019]].
With regard to claims 22-24, Heresco-Levy teaches that the D-amino acid oxidase inhibitor, benzoic acid is administered at a dosage of 500-2000 mg/day, [Claim 14].
With regard to claims 25-26, and 28, Heresco-Levy teaches an example wherein a patient refractory to treatment with various classes of antipsychotic drugs is treated with the different doses of NMDAR agonist while the ongoing antipsychotic medication remained fixed throughout the study of 6 weeks. [Pg. 14-15, [0064-0066]].
With regard to claim 27, Heresco-Levy teaches a method of treating anti-NMDAR encephalitis comprising administering an agent, which is an NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor, D-cycloserine or a combination thereof, [Pg. 7, [0026]]. Heresco-Levy also teaches that the method includes other active agents, [Pg. 12, [0050]]. Administering a combination of NMDAR agonist reads on claim 27 “in combination with an additional active ingredient”.
With regard to claims 29 and 30, Heresco-Levy teaches that the method further comprises combination with immunotherapy, [Pg. 9, [0039]]. The immunotherapy is interpreted as one of the additional therapies taught by the specification. Furthermore, Heresco-Levy teaches that the above patient underwent treatment with antipsychotic drugs and electroconvulsive therapy and no changes in theses medication were performed when the patient treated with different doses of the NMDAR agonist, [Pg. 14, [0064] and Pg. 15, [0066]].
Response to Arguments
Applicant argues:
DAAO inhibitors encompass numerous compounds, and each compound has its own distinct properties. The mere fact that two compounds may be categorized under the broad label of DAAO inhibitors does not establish that they are interchangeable for a specific therapeutic indication, particularly in the absence of evidence showing comparable pharmacological properties, safety profiles, clinical effects, or efficacy in anti-NMDAR encephalitis. Further, the disease addressed in Lane is schizophrenia, which is different from anti-NMDAR encephalitis as discussed in Heresco-Levy. the medicaments used for treating different diseases cannot be readily substituted for one another without clinical evidence. Moreover, Heresco-Levy only exemplifies the effects of D-serine, but fails to prove the effects of benzoic acid in treating anti-NMDAR encephalitis. Since the medical field is highly dependent on experimental evidence, based on the disclosure of Heresco-Levy, a person having ordinary skill in the art would not have reasonably expected benzoic acid to be effective in treating anti-NMDAR encephalitis, let alone have conceived of substituting benzoic acid of Heresco-Levy with sodium benzoate of Lane, which is for treating schizophrenia, and further combining it with IVIg to treat anti-NMDAR encephalitis. It should be noted that the method of Heresco-Levy encompasses numerous pathways that could be involved in the treatment of diseases, and the examples thereof only demonstrate an extremely limited possibility among those pathways (e.g., the effect of D-serine in treating subjects refractory to psychotropic drugs).
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive for the following reasons. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Moreover, "One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."; In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Despite that Lane targets schizophrenia, Lane teaches a method of using D-amino acid oxidase inhibitor, sodium benzoate for treating disorders mediated by hypofunction of the N-methyl-D-aspartate receptor, and Heresco-Levy teaches that anti-NMDAR encephalitis treated by administering D-amino acid oxidase inhibitor. Therefore, the ordinary skilled artisan would have been motivated to use a D-amino acid oxidase inhibitor such as sodium benzoate for treating anti-NMDAR encephalitis. The rationale is that the ordinary skilled artisan would reasonably presume that D-amino acid oxidase inhibitor, sodium benzoate, would produce similar effects to D-amino acid oxidase inhibitor, benzoic acid. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
With regard to Applicant’s argument that “Heresco-Levy does not exemplify the effects of benzoic acid in treating anti-NMDAR encephalitis, Heresco-Levy expressly teaches that NMDAR agonist is D-serine, glycine or the D-amino acid oxidase inhibitor (benzoic acid) [see Heresco-Levy claim 14]. Heresco-Levy provides examples for treating anti-NMDAR Encephalitis using D-serine or glycine, but teaches that “it will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative examples and that the present invention may be embodied in other specific forms without departing from the essential attributes thereof.” [see Heresco-Levy, pg. 21, 0077]. Patents are relevant as prior art for all they contain and “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments.” One of ordinary skill in the art would have been motivated to combine sodium benzoate with immunoglobulin in treating anti-NMDAR encephalitis because Heresco-Levy teaches that intravenous immunoglobulin immunotherapy is the most important components in the treatment of anti-NMDAR encephalitis, and Wang teaches treating patients with anti-NMDAR encephalitis with immunoglobulin immunotherapy as a first-line therapy achieved good outcomes. See the 103 rationale above. Note that Applicant argues Heresco-levy and Lane individually, and one cannot show non-obviousness 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).
Applicant argues:
the subject to be treated by the method recited in amended independent claim 16 is refractory to immune therapy, plasmapheresis and pulse therapy with a steroid. Since neither Heresco-Levy nor Lane mentions the specific clinical condition of the subject recited in the amended claim 16, there is no reason for a person having ordinary skill in the art to arrive at using sodium benzoate in combination with IVIg for treating anti-NMDAR encephalitis in a subject having such clinical conditions.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive for the reasons stated above in the modified obviousness rejection. That is, one of ordinary skill in the art would have been motivated to administer sodium benzoate in combination with intravenous immunoglobulin for treat anti-NMDAR encephalitis in a subject refractory to immune therapy, plasmapheresis and pulse therapy with a steroid because Heresco-Levy teaches that the NMDAR agonist treat subject refractory to pharmacotherapy with presently available antipsychotic drugs and various classes of antipsychotic drugs; Guan teaches that administration of NMDA-agonist, to a patient with anti-NMDAR encephalitis refractory to immunotherapy improved patient’s symptoms gradually and significantly; Wang teaches that anti-NMDAR encephalitis patients are refractory to first line therapy, combination treatment of intravenous methylprednisolone, intravenous immunoglobulin [pg. 61, col. 2, last para. and pg. 62, col. 2, last para.]; Kuppuswamy teaches that second-line and a third-line therapies are required for anti-NMDAR encephalitis patients refractory to corticosteroids, plasma exchange, and intravenous immunoglobulin and for non-responders, [Abstract], and Dengler teaches that most of Anti-NMDAR encephalitis are refractory to immunotherapy with steroids, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (PLEX) and more than 57% of the patients required second-line and third-line therapy. [pg. 38, col. 1, 1st para]. Therefore, refractory to immune therapy, plasmapheresis and pulse therapy with a steroid in patients with anti-NMDAR encephalitis is well known in the art, and it would have been prima facie obvious to one of ordinary skill in the art to administer the sodium benzoate and intravenous immunoglobulin as a second-line therapy.
Applicant argues:
As for Guan, it reports clinical results demonstrating that D-cycloserine, used as a partial NMDA receptor agonist, improved outcomes in anti-NMDAR encephalitis patients who were refractory to first-line and second-line immunotherapies. That is, Guan discloses the use of an NMDA receptor agonist that can improve the activity of NMDAR, so as to compensate for insufficient signaling caused by decreased receptors. It is clear from the above that the DAAO inhibitor (sodium benzoate) disclosed by Lane is totally different from the NMDA receptor agonist (D-cycloserine) disclosed by Guan in the mechanisms for enhancing the function of NMDAR. Specifically, the treatment mechanism of Guan is clearly directed to "directly enhancing the activity of NMDAR" by using an NMDA receptor agonist, rather than "indirectly enhancing co- agonist levels" through DAAO inhibitors. In this regard, since the therapeutic effect of a medicament on a disease is highly unpredictable, for a subject having anti-NMDAR encephalitis as concerned by the present application, it would remain unpredictable whether medicaments acting through different mechanisms would achieve comparable therapeutic effects, even if those medicaments are all intended to enhance the NMDAR function. Accordingly, Guan would not have led a person of ordinary skill in the art to replace D-cycloserine with a DAAO inhibitor, such as sodium benzoate, much less to combine sodium benzoate with IVIg.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Guan was brought in because Guan teaches that administration of N-methyl-D-aspartate (NMDA)-agonist to a patient with anti-NMDAR encephalitis refractory to immunotherapy, improved patient’s symptoms significantly. Thus, Guan would motivate the ordinary skilled artisan to treat anti-NMDAR encephalitis in a subject refractory to immune therapy utilizing Heresco-Levy’s and Lane’s combined method. See MPEP 2143.02. regarding Applicant’s argument that Guan enhancing the activity of NMDAR through different pathway and different mechanisms, As provided in MPEP 2144 (IV). the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). However, in the instant case, despite how Guan is teaching enhancing the activity of NMDAR, Guan teaches administration of N-methyl-D-aspartate (NMDA)-agonist for treating the exact same condition as claimed. Note that Kuppuswamy and Dengler teach that most of patients with anti-NMDAR encephalitis are refractory to corticosteroids, plasma exchange, and intravenous immunoglobulin which would motivate skilled artisan to administer sodium benzoate as second/third line therapy. Regarding Applicant’s statement of unpredictability of therapeutic effect, the cited prior art provides the requisite motivation to one of ordinary skill in the art to administer sodium benzoate to subject with refractory anti-NMDAR encephalitis and obtain predictable results. Additionally, obviousness does not require absolute predictability, but a reasonable expectation of success. See MPEP 2143.02.
Applicant argues:
Wang at most provides background regarding immunotherapy for anti-NMDAR encephalitis, and obviously does not bridge the gap between immunotherapy and the claimed use of sodium benzoate in combination with IVIg for reducing psychotic symptoms in the specific refractory subjects.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive when Wang is combined with the cited references. One of ordinary skill in the art would have been motivated with reasonable expectation of success to combine benzoic salt, sodium benzoate taught by Heresco-levy and Lane with immunoglobulin in treating anti-NMDAR encephalitis because Wang teaches treating patients with anti-NMDAR encephalitis with immunoglobulin immunotherapy as a first-line therapy achieved good outcomes. Moreover, immunoglobulin as taught by Heresco-Levy and Wang is the first-line therapy for anti-NMDAR encephalitis, and benzoate is taught by Heresco-Levy and Lane for treating the very same condition, anti-NMDAR encephalitis, "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, 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).
Conclusion
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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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
1 Additions and modifications have been bolded and underlined.
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