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 38 and 60-78 are under consideration in the instant Office Action.
Withdrawn Objections
The objection of the disclosure is withdrawn in view of the amendments filed on 12/11/2025.
The rejection of claims 38, 60, 63, 65-78 under 35 U.S.C. 102(a)(1) as being anticipated by Boots et al., WO2017/211827 (IDS) is withdrawn in view of newly amended claim 38 which now requires monitoring of p-tau or/and total tau during treatment.
The rejection of claims 38, 60-78 under 35 U.S.C. 103 as being unpatentable over Boots et al., WO2017/211827 (IDS) in view Fassati et al., 2019 (6/13/2025 PTO-892) is withdrawn in view of newly amended claim 38 which now requires monitoring of p-tau or/and total tau during treatment.
Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
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 38, 61-64 and 66-78 are rejected under 35 U.S.C. 103 as being unpatentable over Boots et al., WO2017/211827 (IDS) in view of Hanon et al, 2018 (instant PTO-891) and Fassati et al., 2019 (6/13/2025 PTO-892).
The instant claims are towards a method that administers to a human subject with Alzheimer’s disease an effective amount of an anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab) which is comprised of CDRs SEQ ID NOs:3-8, VH and VL of SEQ ID NOs:1-2 and heavy and light chains SEQ ID NOs: 10-11 and produced the effect of reducing phosphorylated tau (p-tau) and/ or total tau (t-tau) in the human subject.
Boots teaches treating Alzheimer’s patients by administering an effective amount of an anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab, see abstract) as in instant claims 38 and 68-69. Boots teaches the anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab) comprise comprises VH and VL SEQ ID NOs: 1-2 and CDRs SEQ ID NOs:3-8 (see pages 18-19, Tables 1-3 and page 67, claim 1) and sequences SEQ ID NOs: 10-11 (see bottom of page 17 and page 19, Tables 4-5 and page 30) as in instant claims 38 and 70-71.Boots teaches progress can be monitored by periodic assessment during treatment (see page 25, 1st paragraph) as in instant claim 38. Boots teaches administering the antibody via intravenous infusion (see page 22, 2nd paragraph and page 58) as in instant claim 72. Boots teaches administering the antibody at 3mg/ kg, 6mg/kg and/or 10mg/kg of body weight of the human subject (see pages 4, 68, claims 5-7 and 14 ) as in instant claim 73. Boots teaches that multiple doses are administered at interval of 4 weeks (see their claim 16, page 69 and page 30) as in instant claim 74. Boots teaches administering at 4 weeks intervals and ramping up dosage of 1mg/kg, 3mg/ kg, 6mg/kg and/or 10mg/kg of body weight of the human subject over at least 52 weeks (see pages 8-11, 26-27 and 33, claim 35 and Figure 16) as in instant claims 75-76. Boots teaches that the patient population includes ApoE4 carrier and non-carriers (see page 5 (3rd paragraph), page 13, Figure13 and page 71, claim 21) and non-carriers reads on the non-AD associated ApoE3 isotype of instant claim 77. Boots teaches the dosage treatment at low dosages reduces the probability of ARIA (see pages 5) as in instant claim 78 since the antibody treatment does not induce ARIA in non-carriers of ApoE4 (see pages 35, 62, 2nd paragraph; page 64 and page 71). Boots teaches the patient population includes Alzheimer’s disease with prodromal or mild AD (see page 13, Figure 2 and page 63) as in instant claims 38 and 68-69. Boots teaches that AD does not occur in discrete stages, those skilled in the art will recognize that the differences between patient groups may not be distinct in a particular clinical setting and the clinical disease stage can be characterized by measures, and changes in these hallmarks of the disease which include measures over time, such as Ab accumulation (CSF/PET), and tau-mediated neuronal injury in the CSF (include phosphorylated tau and total tau) and clinical function (see page 1, 14 and 53- 54) as in instant claims 63 and 68. Boots teaching of modifying dosage over time in response to positive and adverse effects (see page 36, Table 7, page 53 and bottom of page 54 ) as in instant 66.
Boot teaches that a dose dependent reduction of amyloid was observed and that there was a statistically significant reduction observed at week 26 (see bottom of page 60) and weeks 54 (see page 61). Since Boots has shown that the claimed antibody is capable of reducing one of the biomarkers, amyloid beta, in the same AD population, the intended result of instant claim 67 would also be achieved even if the public was not aware of the intended result. While Boots is silent on the intended result of reducing tau burden when treating AD population with anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab), it is clear that the same patient population would have the same response when administering the instantly claimed composition since there is no evidence to the contrary.
While the references are silent on the intended results in the instant claims, such as reduction of tau, the reference teach the required antibody. Therefore, the antibodies will produce the same results as the instantly claimed method since one is practicing the active steps, administering the same antibody to the same patient population. MPEP 2145(II) states: “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)” (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”). While Boots teaches body fluids (see page 53, 2nd paragraph), Boots does not explicitly teach detecting tau in blood or blood products or monitoring the p-tau or total tau levels as now required in independent claim 38.
Hanon teaches plasma Ab was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose (see abstract). Hanon teaches that there are correlation between the AD and MCI biomarkers in both blood and CSF as required in the instant claims. Hanon teaches that among these biomarkers, cerebrospinal fluid (CSF) Ab42, tau, phosphorylated tau (p-Tau), and cortical amyloid–positron emission tomography (PET) scans have been included in the International Guidelines for AD in clinical research settings (see page 589, 1st column). Hanon teaches blood and lumbar CSF samples for Ab42, tau, phosphorylated tau (p-Tau) are collected on the same day (see page 860, 2.2. Plasma and CSF sampling and analysis). Hanon teaches that there is a relationship between Ab42 and phosphorylated tau (p-Tau), wherein Ab42 has been shown to induce tau phosphorylation or through common mechanisms influencing amyloid and tau metabolism (see page 865, 2nd column). This provides motivation to one of ordinary skill to monitor all of these biomarkers, Ab42, tau and phosphorylated tau (p-Tau), in AD patients being treated to determine the level of effect the treatment is producing in the subject as requires in newly amended claim 38.
Fassati teaches that using plasma tau as a diagnostic for AD is successful and that combining both plasma, a blood product, and CSF levels of phosphorylated (p-tau) and total tau (t-tau) make a better diagnostic for Alzheimer’s disease (see abstract) and meets the limitations of obtaining total tau (t-tau) levels form blood and CSF of instant claims 60-67. Fassati teaches that elevated cerebrospinal fluid (CSF) tau and p-tau are established biomarkers for AD (see page 484, top of 1st column). Fassati teaches obtaining CSF samples via lumbar puncture at the same time blood samples were collected from the same patient (see page 484, 2nd column, 2nd paragraph) and meets the requirement of instant claim 61. Fassati teaches that significantly higher concentrations of plasma tau were found in the AD groups compared with age-matched controls (see page 485, section 3.2) as required in instant claims 61-62, 64 and 68-69. Fassati does not teach treating Alzheimer’s patients by administering an effective amount of an anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab) as required in instant claim 38.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Boots, Hanon and Fassati. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Hanon and Fassati teaches that combining the measurements of amyloid beta and tau levels obtained from CSF and blood samples improve the strength of the biomarkers for AD diagnosis and monitoring. Further, one of ordinary skill in the art would use blood sample to monitor tau levels since the biological fluids of blood are easier and safer to obtain. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
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 38, 61-64 and 66-78 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-63 of U.S. Patent No. 10,842,871 in view of Hanon et al., 2018 (instant PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘871 claims a method of treating Alzheimer’s disease by administering intravenously an effective amount of an anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab) wherein multiple doses of 1 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks, multiple doses of 3 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks, multiple doses of 6 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks, and multiple doses of 10 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks. ‘871 claims detecting a biomarkers selected from the group consisting of total Tau, phospho-Tau, pyroglutamate-Aβ Aβ40, and Aβ42 in cerebrospinal fluid and blood of the human patient. ‘871 does not specifically claim monitoring tau levels when administering the treatment, one of ordinary skill in the art would be motivated to monitor tau and p-tau in view of Hanon’s teachings that Ab levels effect p-tau levels. Therefore, one of ordinary skill in the art would be motivated to monitor all of the possible and well-correlated biomarkers associated in with AD to determine all of the possible effects associated with the instantly claimed treatment method.
While ‘871 is silent on the intended results in the instant claims, such as reduction of tau, ‘871 teaches the required antibody. Therefore, the antibodies will produce the same results as the instantly claimed method since one is practicing the active steps, administering the same antibody to the same patient population. MPEP 2145(II) states: “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)” (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”).
Claims 38, 61-64 and 66-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-68 of copending Application No. 18/607,951 in view of Hanon et al., 2018 (instant PTO-892) and Fassati et al., 2019 (6/13/2025 PTO-892). ‘951 a method of treating Alzheimer’s disease by administering intravenously an effective amount of an anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab) wherein multiple doses of 1 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks, multiple doses of 3 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks, multiple doses of 6 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks, and multiple doses of 10 mg antibody/kg of body weight of the human patient are administered to the human patient at intervals of about 4 weeks. ‘951 fails to teach the claimed biomarkers in blood and CSF as in the instant claims.
‘951 does not specifically claim monitoring tau levels when administering the treatment, one of ordinary skill in the art would be motivated to monitor tau and p-tau in view of Hanon’s teachings that Ab levels effect p-tau levels. Therefore, one of ordinary skill in the art would be motivated to monitor all of the possible and well-correlated biomarker s associated in with AD to determine all of the possible effects associated with the instantly claimed treatment method.
Fassati teaches that using plasma tau as a diagnostic for AD is successful and that combining both plasma, a blood product, and CSF levels of phosphorylated (p-tau) and total tau (t-tau) make a better diagnostic for Alzheimer’s disease (see abstract) and meets the limitations of obtaining total tau (t-tau) levels form blood and CSF of instant claims 60-67. Fassati teaches that elevated cerebrospinal fluid (CSF) tau and p-tau are established biomarkers for AD (see page 484, top of 1st column). Fassati teaches obtaining CSF samples via lumbar puncture at the same time blood samples were collected from the same patient (see page 484, 2nd column, 2nd paragraph) and meets the requirement of instant claim 61. Fassati teaches that significantly higher concentrations of plasma tau were found in the AD groups compared with age-matched controls (see page 485, section 3.2) as required in instant claims 61-62, 64 and 68-69.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of ‘951, Hanon and Fassati. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Fassati teaches that combining the measurements of amyloid beta and tau levels obtained from blood samples improve the strength of the biomarkers for AD diagnosis and monitoring. Further, one of ordinary skill in the art would use blood sample to monitor tau levels since the biological fluids of blood are easier and safer to obtain.
While ‘951 is silent on the intended results in the instant claims, such as reduction of tau, ‘951 teaches the required antibody. Therefore, the antibodies will produce the same results as the instantly claimed method since one is practicing the active steps, administering the same antibody to the same patient population. MPEP 2145(II) states: “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)” (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 12/11/2025 have been fully considered but they are not persuasive. Applicant argues that the present application surprisingly discovered that aducanumab not only attenuates disease-related increases in tau, but also reduces pathological forms of tau in brains of Alzheimer's patients. This is not found persuasive because, as set forth above, Hanon teaches that there is a relationship between Ab42 and phosphorylated tau (p-Tau), wherein Ab42 has been shown to induce tau phosphorylation or through common mechanisms influencing amyloid and tau metabolism (see page 865, 2nd column). Therefore, the applicant’s observation that anti-amyloid beta antibody treatment in the AD subject would also lead to an effect on p-tau is not unexpected or surprising since the prior art already knows that Ab and tau are interconnected and the levels of Ab do have an effect on p-tau.
Further, see MPEP 2112 (I), which states, “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.” Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). See also Verdegaal Bros., Inc. v. Union Oil Co., 814 F.2d 633 (Fed. Cir. 1987) which states "Congress has not seen fit to permit the patenting of an old [composition], known to others…, by one who has discovered its…useful properties."
See MPEP 2112 (I), which states, “The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). The Federal Circuit has stated that ("Congress has not seen fit to permit the patenting of an old [composition], known to others…, by one who has discovered its…useful properties.") See Titanium Metals Corp., 778 F.2d at 782; Verdegaal Bros., 814 F.2d at 628,631 (fed. Cir. 1987). While Boots is silent on the intended result of reducing tau burden when treating AD population with anti-beta-amyloid antibody comprising BIIB037 (aka aducanumab), it is clear that the same patient population would have the same response when administering the instantly claimed composition whether one of ordinary skill is aware how it works or not since the art already provides motivation the administer the instantly claimed antibody treatment to the same patient population, Alzheimer’s patients.
Finally, applicant's request that the double patenting rejections of the instant claims over of the patent be held in abeyance until there is allowable subject matter, at which time they will consider responding is not appropriate. Since applicant has not provided any objections or arguments for the double patenting rejections of record, the above double patenting rejections are maintained.
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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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675