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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 31, 2026 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed August 31, 2026 is acknowledged. Claims 1-59, 61-66, 70-72, 76-79 and 81-90 are cancelled. Claims 60, 73 and 75 are amended. Claims 60, 67-69, 73-75 and 80 are pending in this application and under examination in this office action.
4. Applicant’s arguments filed on August 31, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Priority
5. The priority for the subject matter related to treating NMOSD patients with an elevated GFAP using a B cell depleting therapy including an anti-CD19 antibody and VIB551 (inebilizumab) in the instant application is June 30, 2020.
Claim Rejections/Objections Withdrawn
6. The objection to claim 75 is withdrawn in response to Applicant’s amendment to the claim.
The rejection of claims 73 and 81 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in response to Applicant’s amendment to the claims.
The rejection of claim 73 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn in response to Applicant’s amendment to the claim.
The rejection of claims 81 and 89 under 35 U.S.C. 103 as being unpatentable over Cree et al. (Lancet, 2019; 394:1352-63, as in IDS) in view of Hartung et al. (ACTRIMS Forum 2020, Feb 28; p205:Serum Glial Fibrillary Acidic Protein is elected in a subset of Neuromyelitis Optica Patients and Associated with Increased Risk of Attacks) and Watanabe et al. (Neurology, 2019; 93:e12999-e1311. Doi:10.1212/WNL.0000000000008160).
Claim Rejections/Objections Maintained
In view of the amendment filed on August 31, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 103
7. Claims 60, 67-69, 73-75 and 80 stand rejected under 35 U.S.C. 103 as being unpatentable over Cree et al. (Lancet, 2019; 394:1352-63, as in IDS) in view of Hartung et al. (ACTRIMS Forum 2020, Feb 28; p205:Serum Glial Fibrillary Acidic Protein is elected in a subset of Neuromyelitis Optica Patients and Associated with Increased Risk of Attacks) and Watanabe et al. (Neurology, 2019; 93:e12999-e1311. Doi:10.1212/WNL.0000000000008160). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 60, 67-69, 73-75 and 80 as amended are drawn to a method of treating neuromyelitis optica spectrum disorder (NMOSD) in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of a B cell depleting therapy that is an anti-CD19 antibody which comprises Inebilizumab, wherein a sample of the subject has an elevated serum glial fibrillary acidic protein (sGFAP), and wherein the elevated sGFAP is ≥170pg/ml and the sGFAP concentration decreases following administration of Inebilizumab.
Briefly, Cree teaches a method of treating NMOSD or reducing NMOSD-related damage in a subject in need thereof using Inebilizumab (i.e. an anti-CD19 antibody, B cell depleting therapy) (p. 1353-1354), the method comprising intravenously administering to the subject in need thereof a composition comprising Inebilizumab as recited in independent claims 60 and 75 at a dose of 300mg as recited in claim 73 and repeated every six month as recited in claims 74 and 80 (abstract; p. 1352; p.1354; p. 1357-1361). Cree teaches that the subject is administered a second therapeutic agent including a steroid, plasmapheresis/immunoadsosption or a complement inhibitor or Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, Azathioprine, Mycophenolate Mofetil, or a combination thereof as recited in claims 68-69 (see p. 1352, 2nd col, 2nd paragraph to p. 1354).
While Cree does not explicitly teach that the subject with NMOSD in need of treatment has an elevated sGFAP concentration of ≥170pg/ml recited in independent claims 60 and 75, Hartung and Watanabe teach this limitation and provide motivation and an expectation of success because Hartung and Watanabe teach that sGFAP is a useful biomarker of evaluating attack risk, disease activity and severity of NMOSD, and NMOSD-patients had an increased sGFAP level compared to healthy controls (HC) wherein the elevated sGFAP is defined as ≥3 standard deviations above the HC mean, which is ≥171 pg/mL (see p.1, the section of Results in Hartung) or the median level of sGFAPs in NMOSD patients is 207.7 pg/ml or the median level of sGFAPs in patients with relapse is 540.9 pg/ml, which are ≥170pg/ml (see p. e1299, Abstract; p. e1301-e1303, Tables 1-2; p. e1305-e1307, table 4; p. e1309-e1310; p.e1302, 2nd col., section: association of sGFAP with clinical parameters and p.e1305, 1st col., section: association of sNfL levels with clinical parameters in Watanabe)
The claimed method requires sGFAP ≥170 pg/mL, which overlaps with the ranges of Hartung and Watanabe because Hartung teaches elevated levels of sGFAP ≥171 pg/mL for patients with NMOSD, and Watanabe teaches elevated levels of sGFAP at 207.7 pg/ml or 540.9 pg/ml for patients with NMOSD. Because the claimed range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists.
A person of ordinary skill in the art would have recognized that selecting and applying the known increased levels of sGFAP ≥171 pg/ml or 170 pg/ml in the sample or serum sample of patients with NMOSD as biomarkers of selecting patients with NMOSD and selecting patients with elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml disclosed by Hartung and Watanabe to the Cree’s method would have yielded the predictable result of treating NMOSD and resulted in an improved method because NMOSD patients have elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml as compared to healthy controls, and the elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml are highly associated and correlate with the severity of NMOSD. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known increased levels of sGFAP≥170pg/ml in the sample or serum sample of patients with NMOSD as biomarkers and selecting patients with elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml disclosed by Hartung and Watanabe to the Cree’s method, and yield the predictable result of treating NMOSD based on the elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml. Further, administration of Inebilizumab to NMOSD can treat NMOSD and inherently decrease the levels of the elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml are highly associated and correlate with the severity of NMOSD.
Further, routine optimization of Hartung’s elevated levels of sGFAP ≥171 pg/mL would have led to the claimed range of sGFAP ≥170 pg/mL because Hartung teaches elevated levels of sGFAP ≥171 pg/mL for patients with NMOSD and Watanabe teaches elevated levels of sGFAP at 207.7 pg/ml or 540.9 pg/ml for patients with NMOSD. The person of ordinary skill in the art would have found it obvious to optimize within the range taught by Hartung and Watanabe because Hartung and Watanabe teach that this entire range of elevated sGFAP ≥170 pg/mL, and also teaches how to optimize the levels of elevated sGFAP compared to that of healthy controls. Note that
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”; “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert.denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). See MPEP § 2144.05.
Response to Arguments
On p. 5-6 of the response, Applicant argues that the specification teaches the sGFAP concentrations decreased after treatment of VIB551 for four weeks but not placebo treatment (see Example 7, para. 0251, Figure 8C) and none of the cited references teach that the sGFAP concentration decreases following administration of inebilizuamb.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do teach decreasing sGFAP concentration after administration of inebilizumab and do render the claimed invention obvious because:
i. The limitation “wherein the sGFAP concentration decreases following administration of inebilizumab” is in an inherent result of administration of inebilizumab to NMOSD patients.
Cree teaches a method of treating NMOSD or reducing NMOSD-related damage in a subject in need thereof using the same material (i.e. Inebilizumab) at the same dose (i.e.300mg) and the same active step (i.e. intravenously administering to the subject) in the same patient population (i.e. NMOSD patients) as in instant claims.
If the claimed method can achieve the claimed result of “the sGFAP concentration decreases following administration of inebilizuamb”, the method of Cree that uses the same material at the same dose and the same active step in the same patient population can also achieve the claimed result.
ii. The limitation “wherein the sGFAP concentration decreases following administration of inebilizumab” is in a wherein clause and simply expresses the intended result of a process step “administering of Inebilizumab to the NMOSD patients”, which is not given patentable weight because “the sGFAP concentration decreases following administration of inebilizumab” is the intended result of administration of inebilizumab. See MPEP § 2111.04.
In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005),
….the court noted (quoting Minton v.Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) 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.< See MPEP § 2111.04.
iii. While Cree does not explicitly teach that the subject with NMOSD in need of treatment has an elevated sGFAP concentration of ≥170pg/ml recited in claims 60, 75 and 89, Hartung and Watanabe teach this limitation and provide motivation and an expectation of success because Hartung teaches that patients with NMOSD had an increased sGFAP level compared to that of healthy controls wherein the elevated sGFAP is defined as ≥3 standard deviations above the HC mean (≥171 pg/mL), which is ≥170pg/ml recited in independent claims 60, 75 and 89 and Watanabe that teach the level of sGFAP in patients with NMOSD is higher than that of healthy controls (see p. e1299, Abstract; p. e1301-e1303, Tables 1-2; p. e1305-e1307, table 4; p. e1309-e1310), wherein the median sGFAP levels in patients with NMOSD were 207.7 pg/ml and the median sGFAP levels in patients with relapse were 540.9 pg/ml, which are ≥170pg/ml (see p. e1302, 1st col. section: GFAP levels).
A person of ordinary skill in the art would have recognized that selecting and applying the known elevated level of sGFAP ≥171 pg/ml or 170 pg/ml in the sample of patients with NMOSD as biomarkers for selecting patients with NMOSD and selecting patients with an elevated level of sGFAP ≥171 pg/ml or 170 pg/ml disclosed by Hartung and Watanabe to the Cree’s method would have yielded the predictable result of treating NMOSD and resulted in an improved method because NMOSD patients have an elevated level of sGFAP ≥171 pg/ml or 170 pg/ml as compared to healthy controls, and the elevated level of sGFAP ≥171 pg/ml or 170 pg/ml are highly associated and correlate with the severity of NMOSD.
Using the known increased level of sGFAP≥171 pg/ml or 170 pg/ml as biomarkers and selecting patients with the elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml in the Cree’s method would identify patients with NMOSD for treatment of NMOSD, and would expand application of the Cree’s method, and would increase patient’s satisfaction with treatment using Inebilizumab.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known increased levels of sGFAP≥170pg/ml in the sample or serum sample of patients with NMOSD as biomarkers and selecting patients with elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml disclosed by Hartung and Watanabe to the Cree’s method, and yield the predictable result of treating NMOSD.
Accordingly, the rejection of claims 60, 67-69, 73-75 and 80 under 35 U.S.C. 103 as being unpatentable over Cree in view of Hartung and Watanabe is maintained.
Double Patenting
8. Claims 60, 67-69, 73-75 and 80 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 17, 35, 106, 109-110, 113-114,116-117, 119-121, 124-129 and 133 of copending Application No. 17/606306 (the ‘306 Application), or claims 1, 3, 5, 7-11, 13, 17-18, 31, 39, 46, 53, 62, and 70 of copending Application No. 18/303303 (the ‘303 Application) or claims 1-7, 10-31 and 34-41 of copending Application No. 18997757 (the ‘757 Application) in view of Cree et al. (2019), Hartung et al. (2020) and Watanabe et al. (2019). The rejection is maintained for the reasons of record and the reasons set forth below.
Briefly, the claims of the ‘306 Application, the ‘303 Application or the ‘757 Application claim a method of treating NMOSD using an anti-CD19 antibody including Inebilizumab at a dose of 300mg/ml. while the claims of the ‘306 Application, the ‘303 Application and the ‘757 Application do not recite that the subject with NMOSD in need of treatment has an elevated concentration of sGFAP including at least 170pg/ml recited in independent claims 60, 75 and 89, or administering a second therapeutic recited in claims 68-69, Cree, Hartung, and Watanabe teach these limitations and provide motivation and an expectation of success for the reasons set forth above under the 103 rejection.
Response to Arguments
On 7 of the response, Applicant argues that the present claims are patentably distinct from the claims of the ‘306 Application, the ‘303 Application and the ‘757 Application, and none of the cited references teach that the sGFAP concentration decreases following administration of Inebilizumab for the reasons set forth above.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §804, MPEP §2141, MPEP §2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. For the reasons set forth above, Cree, Hartung and Watanabe teach the limitation “wherein the sGFAP concentration decreases following administration of inebilizumab”. The limitation “wherein the sGFAP concentration decreases following administration of inebilizumab” is in a wherein clause and is an inherent result of administration of inebilizumab to NMOSD patients. If the claimed method can achieve the claimed result of “the sGFAP concentration decreases following administration of inebilizuamb”, the method of Cree that uses the same material at the same dose and the same active step in the same patient population can also achieve the claimed result.
ii. In this case, while the claims of the ‘306 Application, the ‘303 Application and the ‘757 Application do not recite that the subject with NMOSD in need of treatment has an elevated concentration of sGFAP including at least 170pg/ml recited in independent claims 60 and 75, or administering a second therapeutic recited in claims 68-69, Cree, Hartung, and Watanabe teach these limitations and provide motivation and an expectation of success for the reasons set forth above under the 103 rejection. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known increased levels of sGFAP≥170pg/ml in the sample or serum sample of patients with NMOSD as biomarkers and selecting patients with elevated levels of sGFAP ≥171 pg/ml or 170 pg/ml disclosed by Cree, Hartung and Watanabe and the known second therapeutic recited in claims 68-72 disclosed by Cree to the method recited in the claims of the 306 Application, the 303 Application and the ‘757 Application, and yield the predictable result of treating NMOSD, and yield the predictable result of treating NMOSD.
Accordingly, the provisional rejection of claims 60, 67-69, 73-75 and 80 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 17, 35, 106, 109-110, 113-114,116-117, 119-121, 124-129 and 133 of copending Application No. 17/606306, claims 1, 3, 5, 7-11, 13, 17-18, 31, 39, 46, 53, 62, and 70 of copending Application No. 18/303303, or claims 1-7, 10-31 and 34-41 of copending Application No. 18997757 in view of Cree, Hartung and Watanabe is maintained.
Conclusion
8. NO CLAIM IS ALLOWED.
9. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
NCT02200770 (posted 2014-07-24) teaches a method of treating NMOSD or reducing NMOSD-related damage in a subject in need thereof using Inebilizumab (MEDI-551), the method comprising intravenously administering to the subject in need thereof a composition comprising MEDI-551 (i.e. Inebilizumab) at a dose of 300mg and repeated every six month (p. 1; p. 12-14; p. 20-23).
Cree et al. (Multiple Sclerosis J. 2016; 22:862-872) teach a method of treating NMOSD or reducing NMOSD-related damage in a subject in need thereof using Inebilizumab, the method comprising intravenously administering to the subject in need thereof a composition comprising MEDI-551 (i.e. Inebilizumab) at a dose of 300mg and repeated every six month (abstract; p. 862; p. 863; p. 866-871).
Kim et al. (Neurol. Neuroimmunol. Neuroinflamm. 2020; 7:e708. doi:10.1212/NSL000000000000708) teach that the levels of NfL, GFAP and tau in the sera of patients with NMOSD are higher and correlated with the EDSS score (p. 1, abstract; p. 2-6, table 1).
Edwards et al. (ACTRIMS 2018, Poster No. P006) teach that the levels of GFAP, NfL, tau, UCH-L1 are higher in patients with secondary progressive multiple sclerosis (p.1 abstract).
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
September 24, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
