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 .
Continued Examination Under 37 CFR 1.114
1. 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 allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). 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, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on August 4, 2026 has been entered.
2. Claims 1, 3-15, 17-18 and 20 are pending and under examination in the current office action.
The indicated allowability of claims 15, 18 and 20 is withdrawn upon further consideration of the claims as discussed in the rejection below.
Information Disclosure Statement
3. The information disclosure statement filed 08/04/2026 has been considered and the reference therein is now of record.
Specification
4. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See p. 8, line 30 of the Specification filed 06/24/2026. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
5. Claims 4-5 and 11 are objected to because of the following informalities:
Each of claims 4, 5 and 11 recite multiple selections as “a.”, “b.”, “c.” etc., which selection contain periods after each of the letters (i.e., “a”, “b”). MPEP 608.01(m) states that each claim begins with a capital letter and ends with a period, and periods may not be used elsewhere in the claims except for abbreviations. Therefore, it is suggested that claims 4, 5, and 11 be amended to recite “(a)”, “(b)” etc., or else “a)”, “b)” etc.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
6. Claims 15, 18 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treating a tauopathy or diagnosing a patient as one or more of: (i) having a tauopathy, (ii) being at risk of having a tauopathy, (iii) being in need of treatment for a tauopathy, or (iv) being in need of neurological imaging due to having or being suspected of having a tauopathy,
does not reasonably provide enablement for a method of treating or diagnosing any neurodegenerative disease as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
Nature of the invention
The nature of the invention is the development of monoclonal antibodies that are specifically directed to human tau phosphorylated at threonine residue 217 (hTau-pT217), as well as diagnostic applications using these antibodies. As noted by the instant application at p. 1, tau is an axonal microtubule binding protein that promotes microtubule assembly and stability, and is expressed in both the central and peripheral nervous systems (CNS and PNS, respectively). Hyperphosphorylated forms of human tau are known to be involved in the abnormal formation and aggregation of intraneuronal neurofibrillary tangles (NFTs) within the CNS, and are associated with neurodegenerative diseases such as Alzheimer’s disease (AD), Progressive Supranuclear Palsy (PSP), and Frontal Temporal Dementia (FTD) (also collectively known as tauopathies).
Breadth of the claims
Claim 15 is drawn to a method of treating a neurodegenerative disease in a patient in need thereof, comprising detecting binding of an antibody that specifically binds hTau-pT217 in a sample from the patient and administering a therapeutically effective amount of an antibody that binds to amyloid beta or tau. Claims 18 and 20 are drawn to a method of diagnosing a patient as having a neurodegenerative disease (ND), being at risk for having an ND, being in need of treatment for an ND, or being in need of neurological imaging comprising detecting binding of an antibody which specifically binds hTau-pT217 and an antibody that specifically binds CNS-expressed isoforms of human tau in a sample from the patient. Thus, the claims broadly encompass the treatment and diagnosis of any neurodegenerative disease using an antibody that is specific for only one type of protein (hTau-pT217) that is associated with one type of neurodegenerative disease (i.e., tauopathies).
However, the term neurodegenerative disease encompasses not only the tauopathies of AD, PSP and FDT as described in the instant specification, but also numerous other diseases and disorders that are not recognized as being linked to the presence or accumulation of hTau-pT217. These diseases include, among others, such NDs as: Huntington’s disease (HD), which is a genetic disorder caused by a gene variant or mutation in the huntingtin gene; Parkinson’s disease (PD), in which CNS neurodegeneration is associated with the presence of Lewy bodies, which are formed by abnormally aggregated alpha-synuclein protein; multiple sclerosis (MS), which is a chronic autoimmune disease of the CNS associated with neuroinflammation and the loss of myelin; Amyotrophic lateral sclerosis (ALS), a motor neuron disease causing progressive muscle wasting and weakness, and is neuropathologically characterized by inclusion bodies of TDP-43 protein (or SOD1 or FUS protein in patients with SOD1 or FUS mutations); and Prion diseases such as Creutzfeldt-Jakob disease, caused by misfolded prion protein. Importantly, other than tauopathy-type NDs, none of the other NDs are generally recognized as being caused by or otherwise associated with the presence of phosphorylated tau, such as hTau-pT217.
Relative skill of those in the art
The relative skill of those in the art is high, generally at a postgraduate level, such as a person having a master’s degree, a medical degree (MD), a doctorate (PhD, DPhil), or other similarly skilled researcher or clinician.
Amount of direction or guidance provided
The instant application describes the how to make and use monoclonal antibodies that specifically bind hTau-pT217 in various immunoassays. The specification also provides general information on formulating pharmaceutical compositions comprising the antibodies, and the diagnostic application of the hTau-pT217 antibody.
Presence or absence of working examples
The specification describes the generation and characterization of monoclonal antibodies that specifically bind hTau-pT217, and provides several immunoassays using the antibodies to detect hTau-pT217 in plasma, serum and cerebrospinal (CSF) samples of AD patients.
However, there are no examples demonstrating the diagnosis of any neurodegenerative disease other than AD, nor the detection of hTau-pT217 in any disease other than AD. There is no evidence of record showing that hTau-pT217 is present in, for example, a sample obtained from a patient having HD, ALS, MS, PD, prion disease, or any other ND.
State of the art and Predictability or unpredictability of the art
As discussed above, the state of the art at the time of filing generally recognized that hyperphosphorylated tau was present in, and potentially causative of, the neurodegeneration found in tauopathies such as AD, PSP and FTD. However, there was no art-recognized nexus between phosphorylated tau protein, such as hTau-pT217, and other non-tauopathy neurodegenerative diseases such as PD, HD, MS, ALS or prion disease, as above. See, for example, the review by Kovacs (J. Clin Pathol. 2019, 72:725-735) which describes the molecular neuropathology of the different NDs and the causative proteins associated with each ND. And while Kovacs notes that the different NDs may show various degrees of comorbid proteinopathies, this does not evidence or otherwise suggest that tau, or hTau-pT217 specifically, can be reliably detected in any ND (other than a tauopathy) or that reduction in the levels or amount of hTau-pT217 (as in case of treatment with an anti-hTau-pT217 antibody) would be at all effective in non-tauopathy NDs.
Accordingly, undue experimentation would be required of the skilled artisan to test the ability of the claimed hTau-pT217 antibody to reliably diagnose other non-tauopathy types of NDs and/or treat non-tauopathy type ND with a reasonable expectation of success.
Quantity of experimentation necessary
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In view of the breadth of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability as evidenced by the prior art, and the amount of required experimentation, it is the examiner’s position that undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to practice the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir., 1988).
Conclusion
7. Claims 15, 18 and 20 are rejected.
Claims 1, 3, 6-10 and 12-14 are allowed.
Claims 4-5 and 11 are objected to for minor informalities. Claim 17 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly A. Ballard whose telephone number is (571)272-2150. The examiner can normally be reached Mon-Fri 8AM - 5PM EST.
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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.
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
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