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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 9, 2026 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed April 9, 2026 is acknowledged. Claims 1-44, 46, 53, 55 and 60-66 are canceled. Claim 45 is amended. Claims 45, 47-52, 54, 56-59 and 67-73 are pending in this application. The election was made without traverse (filed 7/11/16) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
4. Claims 45, 47-52, 54, 56-59 and 67-73 are under examination with respect to SEQ ID NO:2 in this office action.
5. Applicant’s arguments filed on April 9, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
6. The rejection of claims 45, 47-52, 54, 56-57 and 67-73 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Westbrook (US7897361) in view of Thambisetty et al. (Arch Gen Psychiatry, 2010; 67:739-748), Sihlbom et al. (Intl. J. Mass Spec. 2004; 234;145-152) and Kapron et al. (Protein Science 1997; 6:2120-2133) is withdrawn in response to PTAB’s decision dated 11/21/2025.
The rejection of claims 58-59 under 35 U.S.C. 103 as being unpatentable over Westbrook (US7897361) in view of Thambisetty et al. (2010), Sihlbom et al. (2004) and Kapron (1997) as applied to claims 45, 47-52, 54-57 and 67-73 above, and further in view of Aebersold et al. (WO2008066629) is withdrawn in response to in response to PTAB’s decision dated 11/21/2025.
The rejection of claims 45, 47-52, 54, 56-59 and 67-73 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more is withdrawn in response to Applicant’s amendment to the claims.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on April 9, 2026.
Claim Objections
7. Claim 45 is objected to because of the following informalities: the limitation “an -N-acetyl-glucosaminidase inhibitor” should be “a -N-acetyl-glucosaminidase inhibitor”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 45, 47-52, 54, 56-59 and 67-73 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 45, 47-52, 54, 56-59 and 67-73 are indefinite because:
i. Claim 45 recites the limitation "the administration" in line 14 of the claim. There is insufficient antecedent basis for this limitation in the claim.
ii. There is no subject for the step of administering recited in claim 45.
iii. It is unclear whether the limitation “said first concentration, amount or degree of expression” recited in claim 45 and the limitation “the first concentration, amount or degree of expression” refer to the same concentration, amount or degree of expression, which renders the claim indefinite. The same issue applies to the limitations ““said second concentration, amount or degree of expression” and “the second concentration, amount or degree of expression” and the limitations “said at least one specific glycoform derived from the clusterin precursor or fragment thereof” and “said at least one specific glycoform derived from the clusterin precursor or fragment thereof” recited in claim 45 and dependent claims. The recitation can be obviated by amending the limitation “said….” to the limitation “the….”.
iv. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
9. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 45, 47-52, 54, 56-59 and 67-73 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 detecting reduced levels of a glycosylated fragment of a beta chain of human clusterin of SEQ ID NO:2 having a N-linked glycan attached to asparagine 64 (“64N-glycan”) with the features recited in independent claim 45 in a sample of plasma from patients with Alzheimer’s disease (AD) as compared to that from patients with mild cognitive impairment (MCI) using the steps (i)-(iv) recited in claim 45, does not reasonably provide enablement for a method for determining whether the subject has AD comprising the steps (i)-(iv) above and (v) treating the test subject who has determined as having AD by administration of an effective amount of all forms of structurally and functionally undefined b-N-aceyl-glucosaminidase inhibitors 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 use the invention commensurate in scope with these claims. In addition, the specification does not enable the invention of claims 1-3 that is directed to a method of prevention.
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is 'undue'. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)”. See MPEP § 2164.01.
Claims 45, 47-52, 54, 56-59 and 67-73 as amended are drawn to a method for determining whether a test subject has Alzheimer's disease (AD), comprising:
(i) providing a protein-containing blood plasma sample that has been obtained from the test subject;
(ii) determining a first concentration, amount or degree of expression of at least one specific glycoform derived from a clusterin precursor or fragment thereof, in the blood plasma sample, using trypsin digestion followed by mass spectrometry or Selected Reaction Monitoring (SRM);
(iii) detecting a difference between the first concentration, amount or degree determined in (ii) and a second concentration, amount or degree of the at least one specific glycoform derived from the clusterin precursor or fragment thereof, in a protein-containing sample obtained from a control subject with Mild Cognitive Impairment (MCI);
(iv) determining that the test subject has AD when the first concentration, amount or degree determined in (ii) is reduced in comparison to the second concentration, amount or degree; and
(v) treating the test subject for AD by the administration of an effective amount of a b-N- acetyl-glucosaminidase inhibitor;
wherein the at least one specific glycoform derived from the clusterin precursor or fragment thereof comprises the sequence of SEQ ID NO:2, and is a glycosylated fragment of a beta chain of human clusterin having the sequence set forth in SEQ ID NO: 1, having an N-linked glycan attached to asparagine 64 (" p64N-glycan"), wherein the N-linked glycan is selected from the group consisting of:SA1-(HexNAc-Hex)2-core; SA2-(HexNAc-Hex)2-core; SA1-(HexNAc- Hex)3-core; SA2-(HexNAc-Hex)3-core; SA1-(HexNAc-Hex)4-core; SA3 -(HexNAc-Hex)3 -core; SA2-(HexNAc-Hex)4-core; and SA3-(HexNAc-Hex)4-core, wherein "SA" is a sialic acid, "HexNAc" is an N-acetylhexoseamine, "Hex" is a hexose and "core" is the N-linked glycan core sugar sequence Man3GlcNAc2AsnU.
The instant specification is based on findings of detection of reduced levels of a glycosylated fragment of a beta chain of human clusterin of SEQ ID NO:2 having a N-linked glycan attached to asparagine 64 (“64N-glycan”) wherein the N-glycan link is selected from the group recited in independent claim 45 in a sample of plasma from patients with Alzheimer’s disease (AD) as compared to that from patients with mild cognitive impairment (MCI) (see Example 1-6).
Applicant extrapolates the above findings to the claimed method for determining whether a test subject has AD based on detecting a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof in the test subject compared to that of a MCI control wherein the at least one specific glycoform derived from the clusterin precursor or fragment thereof comprises a glycosylated fragment of a beta chain of human clusterin having the sequence set forth in SEQ ID NO:2 having an N-linked glycan attached to asparagin 64 (64N-glycan) and also treating the test subject for AD by administration of a b-N- acetyl-glucosaminidase inhibitor.
However, neither the specification nor the prior art teaches that administration of any b-N-acetyl-glucosaminidase inhibitor including structurally and functionally defined or undefined b-N-acetyl-glucosaminidase inhibitor can treat AD.
While the skill level in the art is high, the level of predictability is low. Hering et al. teach that based on phase I or phase II clinical trial of a b-N-acetyl-glucosaminidase inhibitor, a phase I clinical trial of BIIB113 (a b-N-acetyl-glucosaminidase inhibitor) in treatment of AD and a phase II clinical trial of ceperognastat in treatment of AD had been discontinued (see p. 11, Table 2, Hering et al. Molecular Neurodegeration, 2025; 20:88. Doi.org/10.1186/s13024-025-00872-7). Fleisher et al. teach that while ceperognastat (LY3372689), an orally available -N-acetyl-glucosaminidase inhibitor (also called O-GlcNAcase inhibitor or OGA inhibitor), has been shown to slow the accumulation of hyperphosphorylated, insoluble tau, including neurofibrillary tangles in animal models of tauopathy, treatment of AD with ceperognastat did not result in any clinical benefits of slowing progression in early symptomatic AD; and rather ceperognastat worsened the progression of AD at 3mg and resulted in a higher incidence of adverse events when compared to placebo based on PROSPECT-ALZ (NCT05063539), a multicenter, double-blind, randomized placebo-controlled phase 2 study of ceperognastat in AD (p. 1, Fleisher et al. 17th Clinical Trials on Alzheimer’s Disease (CTAD) Madrid, Spain, October 29 - November 1, 2024: Symposia, Oral Communications ”; J Prev Alzheimers Dis 2025;12(1S):100043).
The specification provides no guidance as to what other -N-acetyl-glucosaminidase inhibitors that can treat AD are. The specification provides no guidance as to whether all -N-acetyl-glucosaminidase inhibitors including structurally and functionally undefined -N-acetyl-glucosaminidase inhibitors can be used in the claimed method because a single amino acid change on a molecule can abolish the binding ability or activity of the molecule. For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210).
The specification fails to teach what structures of other -N-acetyl-glucosaminidase inhibitors that can be used for treatment of AD are and what common structures/amino acid sequences can or cannot be included/changed in all -N-acetyl-glucosaminidase inhibitors in order to preserve the activity of ceperognastat or BIIB113 in slowing accumulation of hyperphosphorylated, insoluble tau, including neurofibrillary tangles in animal models of tauopathy or in generation of reduced or increased levels of at least one specific glycoform derived from the clusterin precursor or fragment thereof recited in claim 45 in a sample of plasma from patients with AD compared to that from patients with MCI or even in treatment of AD. It is unpredictable what the claimed b-N- acetyl-glucosaminidase inhibitors are, what amino acids or structures of the claimed b-N- acetyl-glucosaminidase inhibitors are and whether the structurally and functionally undefined or b-N- acetyl-glucosaminidase inhibitors or other structurally and functionally defined can be used for treating AD or a test subject who has been diagnosed as having AD based on a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention. Thus, a skilled artisan cannot contemplate how to make and use the claimed invention because neither the specification nor the prior art teaches that the structural and functional relationship or correlation between treatment of AD with the claimed structurally and functionally undefined b-N- acetyl-glucosaminidase inhibitor and the test subject with a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control.
Therefore, in view of the lack of guidance in the specification, the unpredictability of the inventions, the lack of working example, the breadth of the claims, and the current status of the prior art, undue experimentation would be required of a skilled artisan to perform in order to practice the claimed invention as it pertains to a method for administering a b-N- acetyl-glucosaminidase inhibitor for treatment of AD based on a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control as recited in claim 45 as instantly claimed.
Claim Rejections - 35 USC § 112
10. Claims 45, 47-52, 54, 56-59 and 67-73 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 45, 47-52, 54, 56-59 and 67-73 as amended encompass using a genus of b-N- acetyl-glucosaminidase inhibitor for treatment of AD based on a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control as recited in claim 45.
Applicant has not disclosed sufficient species for using the broad genus of b-N- acetyl-glucosaminidase inhibitor for treatment of AD based on a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control as recited in claim 45.
The specification only describes detection of reduced levels of a glycosylated fragment of a beta chain of human clusterin of SEQ ID NO:2 having a N-linked glycan attached to asparagine 64 (“64N-glycan”) wherein the N-glycan link is as recited in independent claim 45 in a sample of plasma from patients with Alzheimer’s disease (AD) as compared to that from patients with mild cognitive impairment (MCI) (see Example 1-6).
However, the claims are not limited to the method set forth above but also encompass treatment of AD using a genus of b-N-acetyl-glucosaminidase inhibitor for treatment of AD in a test subject who has been determined as having AD based on a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control as recited in claim 45.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of a method of detecting reduced levels of at least one specific glycoform derived from the clusterin precursor or fragment thereof recited in claim 45 in a sample of plasma from patients with AD compared to that from patients with MCI (see Example 1-6). However, Applicant is not in possession of the claimed method including treating a test subject with AD based on a reduced level of at least one specific glycoform derived from the clusterin precursor or fragment thereof compared to that of a MCI control as recited in claim 45 using a genus of structurally and functionally undefined b-N-acetyl-glucosaminidase inhibitors.
Hering et al. teach that based on phase I or phase II clinical trial of a b-N- acetyl-glucosaminidase inhibitor, a phase I clinical trial of BIIB113 (a b-N-acetyl-glucosaminidase inhibitor) in treatment of AD and a phase II clinical trial of ceperognastat in treatment of AD had been discontinued (see p. 11, Table 2, Hering et al. Molecular Neurodegeration, 2025; 20:88. Doi.org/10.1186/s13024-025-00872-7). Fleisher et al. teach that while ceperognastat (LY3372689), an orally available -N-acetyl-glucosaminidase inhibitor, has been shown to slow the accumulation of hyperphosphorylated, insoluble tau, including neurofibrillary tangles in animal models of tauopathy, treatment of AD with ceperognastat did not result in any clinical benefits of slowing progression in early symptomatic AD; and rather ceperognastat worsened the progression of AD at 3mg and resulted in a higher incidence of adverse events when compared to placebo based on PROSPECT-ALZ (NCT05063539), a multicenter, double-blind, randomized placebo-controlled phase 2 study of ceperognastat in AD (p. 1, Fleisher et al. 17th Clinical Trials on Alzheimer’s Disease (CTAD) Madrid, Spain, October 29 - November 1, 2024: Symposia, Oral Communications ”; J Prev Alzheimers Dis 2025;12(1S):100043).
The specification provides no identification of any particular portion of the structure of the claimed genus of b-N-acetyl-glucosaminidase inhibitors that must be conserved in order to treat AD. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of b-N-acetyl-glucosaminidase inhibitors. There is no description of the conserved regions which are critical to the function of the genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of structure of b-N-acetyl-glucosaminidase inhibitors that can treat AD is and there is no information regarding the relation of the structure of other b-N-acetyl-glucosaminidase inhibitors to the function of BIIB113 or ceperognastat in slowing the accumulation of hyperphosphorylated, insoluble tau, including neurofibrillary tangles in animal models of tauopathy or in generation of reduced levels of at least one specific glycoform derived from the clusterin precursor or fragment thereof recited in claim 45 in a sample of plasma from patients with AD as compared to that from patients with MCI or even in treatment of AD. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other b-N-acetyl-glucosaminidase inhibitors that can treat AD might be.
Since the common characteristics/features of b-N-acetyl-glucosaminidase inhibitors that can treat AD are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of b-N-acetyl-glucosaminidase inhibitors that can treat AD.
As stated in M.P.E.P. § 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321,1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
Whereas a reduction to practice of an uncomplicated invention such as a simple mechanical or electrical device can be achieved by merely providing a diagram of the device wherein one skilled in the relevant art can predict the likely operability of the device by reviewing the diagram, the operability of the claimed invention cannot be predicted by merely reviewing diagrams or illustrations. To demonstrate the reduction to practice of a step or method of treating an animal by the administration of -N-acetyl-glucosaminidase inhibitor requires either a working embodiment, a demonstration of operability in the treatment of an art accepted animal model of the condition to be treated wherein that animal model has been shown to be reliably predictive of efficacy in the treatment of the condition, or a demonstration that the therapeutic agent employed therein possesses an activity in which the majority of compounds possessing that activity have been shown to be effective in the treatment of that condition. In the instant case, Applicant has provided none of these. Consequently, Applicant has failed to demonstrate possession of the claimed method or even a single species of the genus of -N-acetyl-glucosaminidase inhibitor required thereby as of the earliest effective filing date of the instant application.
With respect to the demonstration of a reduction to practice of a generic invention, M.P.E.P. § 2163(II)(A)(3)(ii) states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus, above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that; “ It appears to be well settled that a single species can rarely, if ever, afford support fora generic claim. In re Soil, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867,117 F.21 270,48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention, and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
In the instant case, Applicant has failed to demonstrate a reduction to practice of a representative number species of the genus “-N-acetyl-glucosaminidase inhibitor”, or even a single species within that genus, much less a method of treating a subject afflicted with AD by the administration of such -N-acetyl-glucosaminidase inhibitors thereto. The experimental results described in the specification consist primarily of detecting reduced levels of at least one specific glycoform derived from the clusterin precursor or fragment thereof recited in claim 45 in a sample of plasma from patients with AD compared to that from patients with MCI (see Example 1-6). Those results do not support a conclusion that Applicant was in possession of a method of treating a test subject with AD by the administration of a -N-acetyl-glucosaminidase inhibitor wherein the AD is determined based on reduced levels of at least one specific glycoform derived from the clusterin precursor or fragment thereof recited in claim 45 in a sample of plasma from patients with AD compared to that from patients with MCI.
There is no structural and functional relationship or correlation between the claimed genus of -N-acetyl-glucosaminidase inhibitors and BIIB113 or ceperognastat in slowing the accumulation of hyperphosphorylated, insoluble tau, including neurofibrillary tangles in animal models of tauopathy or in generation of reduced levels or increased levels of at least one specific glycoform derived from the clusterin precursor or fragment thereof recited in claim 45 in a sample of plasma from patients with AD as compared to that from patients with MCI or even in treatment of AD.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of -N-acetyl-glucosaminidase inhibitors for treatment of AD, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed method has not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Conclusion
11. NO CLAIM IS ALLOWED.
12. 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.
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Chang-Yu Wang
May 30, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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