Detailed Action
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Restriction/Election
Applicant’s election without traverse of Group I (i.e., claims 1, 2, 9, 13-15, and 20) and Species A (i.e., Seq ID Nos: 8, 9, 13, 14, 16, 17, 20, and 26) in the reply filed on 7 August 2025 is acknowledged.
Status of the Claims
Claims 1-23 were originally filed 1 December 2021. The preliminary amendment filed 8 July 2022 has been entered. Claims 10, 11, and 21-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group (i.e., peptide), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7 August 2025. Claims 1, 2, 9, 13-15, and 20 are currently under consideration.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., see specification pg. 25 para [0029], pg. 64 para [0087], figure 1). 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 Rejections - 35 USC § 112(a)
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.
Claims 1, 2, 9, 13-15, 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 the following:
Claim 1. A therapeutic agent for tauopathies,
Claim 2. A therapeutic agent for tauopathies according to claim 1, wherein the therapeutic agent is an anti-tau antibody comprising specific sets of complete VH and VL domains (e.g., Seq ID Nos: 20 and 26), and
Claim 15. A monoclonal antibody that specifically binds a peptide comprising a sequence at least 8 contiguous amino acids from the amino acid sequence consisting of amino acid numbers 410-421 of Seq ID No: 1, wherein the amino acid residue Ser4 in the peptide is phosphorylated and wherein the monoclonal antibody comprises specific sets of complete VH and VL domains (e.g., Seq ID Nos: 20 and 26)
does not reasonably provide enablement for i. a prophylactic agent (claim 1), ii. all cognitive disorders (claim 1), iii. an antibody which competes with an antibody including a VH consisting of Seq ID No: 20 and a VL consisting of Seq ID No: 26 (claim 2(iii), claim 15(i)), iv. an antibody including a VH consisting of Seq ID No: 20 and a VL consisting of Seq ID No: 26 (claim 2(iv), claim 15(ii)), v. an antibody comprising less than 6 CDRs (e.g., one of, at least one of, at least 85% homology) (claim 2(vi)(vii), claim 15(iii)), vi. an antibody comprising either a VH or VL or any combination of Seq ID Nos (claim 2(vii), claim 15(iv)), or an antibody that binds one or more of Ser412, Thr414, and Ser416 (see claim 2(ii)). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 Fed 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, and the unpredictability in the art to enable one of skill in the art to make and use the claimed invention.
Breadth of the Claims
Claim 1 is drawn broadly to a therapeutic or prophylactic agent for cognitive disorders comprising an active ingredient wherein the active ingredient is an antibody capable of binding to tau protein phosphorylated at one position among positions 410 to 421 of Seq ID No: 1. The specification does not provide a limiting definition for prophylactic agent however does teach,
“The therapeutic agent or prophylactic agent for cognitive disorders of the invention may also be considered to have an effect of improving cognitive function or inhibiting loss or maintaining cognitive function in non-human animals” (see specification pg. 34 para [0041]), and
“The therapeutic or prophylactic agent for cognitive disorders according to the invention also encompasses the concept of a therapeutic agent or prophylactic agent comprising existing substances with effects of inhibiting developments of cognitive disorders” (see specification pgs. 49-50 para [0049]).
Prophylactic is defined as guarding from or preventing the occurrence of disease (see Definitions: Prophylactic, Merriam Webster, accessed online 15 September 2025) (see MPEP § 2111). The specification defines cognitive disorders in humans as “a condition of impairment in the intellectual function that has been developed or acquired, and it is considered a type of intellectual disturbance, and in a wider sense they are considered diseases exhibiting intellectual disturbance and/or memory impairment (see specification pg. 32, starting on line 15). Therefore, the language of claim 1 encompasses an agent capable of up to 100% prevention of any developed or acquired impairment in intellectual function (e.g., concussion). The antibody must bind tau protein that is phosphorylated on at least one amino acid residue among positions 410-421 of tau protein represented by Seq ID No: 1. It is noted the language of claim 1 does not limit the scope of the antibody to binding only a phosphorylated form of tau protein nor to the particular residues (i.e., epitope specific) in Seq ID No: 1; therefore, claim 1 encompasses antibodies capable of binding any location on any tau protein isoform comprising the particular residues instantly claimed (i.e., 410-421 of Seq ID No: 1) in either a phosphorylated or unphosphorylated form. It is noted the specification also teaches the particular residues instantly claimed (i.e., 410-421 of Seq ID No: 1) are present in multiple tau protein isoforms (e.g., Ser413 in Seq ID No: 1 (tau isoform 4R2N) corresponds to Ser384 in Seq ID No: 2 (tau isoform 4R1N)).
Claim 2 is additionally drawn to several embodiments of the claimed antibody all set forth in the alternative (i.e., “or”). For example, wherein the antibody which competes with an antibody including a VH consisting of Seq ID No: 20 and a VL consisting of Seq ID No: 26 (claim 2(iii)), iv. an antibody including a VH consisting of Seq ID No: 20 and a VL consisting of Seq ID No: 26 (claim 2(iv)), v. an antibody comprising less than 6 CDRs (e.g., one of, at least one of, at least 85% homology) (claim 2(vi)(vii)), or vi. an antibody comprising either a VH or VL or any combination of Seq ID Nos (claim 2(vii)). It is noted claim 2(iii) and (iv) are drawn to “an antibody including VH consisting of the amino acid sequence listed as Seq ID No: 20 and VL consisting of the amino acid sequence listed as Seq ID No: 26”. In so far as the language “antibody including” is intended to set forth a specific embodiment i.e., an antibody with a VH consisting of the amino acid sequence listed as Seq ID No: 20 and VL consisting of the amino acid sequence listed as Seq ID No: 26, the language of claim encompasses an antibody with only these two regions. The language of claim 2(vi) and (vii) are drawn to antibodies comprising as little as 1 CDR with 85% homology or antibodies with 85% homology to either a VH or VL which encompasses highly variable CDRs. Similarly, claim 2(iii) drawn antibodies that compete with a particular antibody encompasses a genus of anti-tau antibodies including human, humanized, or murine antibodies in any format (e.g., VHH, Fab, scFv, or full length), comprising any CDRs wherein the only two functional requirements are binding anywhere on tau when phosphorylated at any position between amino acids 410-421 of Seq ID No: 1 and either directly (e.g., binding the same epitope) or indirectly (e.g., binding affinity, steric hinderance) of a particular antibody.
Claim 15 is similar to claim 2 in that both claim are drawn to particular embodiments of the anti-tau antibody. However, claim 15 is also drawn to a monoclonal antibody that participates in antigen-antibody reaction with a peptide comprising (i.e., open language) a sequence of at least 8 contiguous amino acids from the sequence consisting of amino acid number 410-421 of Seq ID NO: 1 wherein the 4th serine in residues 410-421 is phosphorylated. Therefore, the language of claim 15 encompasses any monoclonal antibody that can bind to tau, given tau is a peptide that comprises amino acids 410-421 of Seq ID No: 1.
It is noted, the claims are drawn to a therapeutic agent wherein the therapeutic agent comprising an active ingredient wherein the active ingredient is an antibody (see claim 1 line 2). The specification does not provide a limiting definition for antibody. Pursuant to MPEP § 2111 the broadest reasonable interpretation of antibody at the time of filing includes single domain antibodies (i.e., VH only) (see Saerens et al. (2008) Single-domain antibodies as building blocks for novel therapeutics. Current Opinion in Pharmacology, 8: pgs. 600-608, in particular pg. 600, 2nd col. 3rd para).
Amount of Direction or Guidance Provided
The specification discloses Cognitive disorders can be classified as neurodegenerative diseases, vascular cognitive disorders, prion diseases, infectious diseases, metabolic/endocrine disorders, trauma and cerebral disorders, and toxic disorders (see specification pg. 1 para [0002]). Tauopathies are diseases caused by intracellular accumulation of tau and include neurodegenerative diseases (e.g., Alzheimer’s disease (AD)), non-neurodegenerative diseases (e.g., von Economo’s postencephalitic Parkinson’s disease), and trauma-induced conditions (e.g., boxer’s encephalopathy) (see specification pg. 2 para [0003]). Some tauopathies are genetic including chromosome 17-linked frontotemporal dementia with Parkinsonism (FTDP-17) (see specification pg. 3 para [0004]).
Tau is a microtubule-binding protein highly expressed in the central nervous system and is a major component in neurofibrillary tangles (NFT) (see specification pg. 2 para [0003]). Accumulation of tau in neurodegenerative diseases is due to modified phosphorylation (see specification pg. 4 para [0005]). However, Applicant discloses fetal and normal human brains also express similarly phosphorylated forms of tau as brains with neurodegeneration (see specification pg. 4 para [0005]). This is also supported by the state of the art which discloses Ser412, 413, 416 and Thr414 are all phosphorylated in both Alzheimer Disease brains and healthy brains (see Colwell and Emborg (2025) Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders. Front. Aging Neurosci. 17:1598245, pg. 5 Table 1). Upon excessive intracellular phosphorylation tau is secreted from the cell and interacts with muscarine receptors which promote intracellular tau phosphorylation and ultimately elicits cell death (see specification pgs. 4-5 para [0006]). Applicant cautions secreted phosphorylated tau may undergo dephosphorylation once secreted from the cell or may be further modified (see specification pg. 5 para [0006]). Therapeutic agents that target portions of dephosphorylated tau can affect the function of normal tau and subsequently exhibit undesirable side effects. Therefore, it is important to target pathology-associated tau which requires identifying an epitope associated with said pathology (e.g., a tau phosphorylation epitope) and engineering an agent specific to said epitope, a process Applicant discloses, “becomes even more difficult due to the complexity” of tau activity (e.g., trafficking, modifications) (see specification pg. 6 para [0006]). Applicant discloses additional obstacles involved in identifying therapeutic antibodies include the route of administration due to the difficulty in traversing the blood brain barrier and the amount of the antibody to be administered (see specification pg. 7 para [0008]).
Limited Working Examples
Applicant has provided 8 antibodies (i.e., 1 polyclonal and 8 monoclonal) anti-phosphorylated tau antibodies, wherein the antibodies specifically recognize a phosphorylated serine at position 413 of Seq ID No: 1 or phosphorylated serine at positions 396 and 404 of Seq ID No: 1 (see specification pg. 45 para [0059], figure 3, pg. 50 para [0065], Table 2, pg. 55 para [0075]). Applicant demonstrates all 10 antibodies detect their respected phosphorylated versions of tau (see specification pg. 45 para [0059], pg. 50 para [0065], pg. 56 para [0076]). The polyclonal (i.e., pSer413), Ta1505 antibody (i.e., pSer413 monoclonal), and Ta9 antibody (i.e., pSer396) were administered to Tau-Tg mice and all showed improved memory impairment (see specification pg. 61 line 25-pg. 66 line 13, figures 4, 8, and 12). Despite antibody Ta9 having increased affinity for the pSer396 epitope over the affinity of antibody Ta1505 for pSer413 antibody Ta9 did not perform as well (see specification pg. 62 lines 14-19, figure 12). Applicant suggests, “a significant difference in the drug effect due to differences in the phosphorylation epitope” (see specification pg. 62 lines 17-19). Memory improvement was seen with as little as .1mg doses of Ta1505 in Tg mice whereas Ta9 treatment at the same dose exhibited no memory improvement (see specification pg. 67 lines 20-35 figures 18-21). Therefore, Applicant has demonstrated that an antibody that binds tau phosphorylated at serine 413 of Seq ID No: 1 can improve memory impairment in Tg mice and the affinity of the antibody for its phosphorylated target does not correlate with its efficacy to improve memory impairment. The 7 monoclonal pSer413 antibodies (i.e., Ta1501-1509 discloses by Applicant all have the same LCDRs 1-3 except Ta1509 wherein LCDR1 differs by 1 amino acid and all have the same HCDR3, 1 of 2 HCDR1s (i.e., differ by 1 amino acid), and 1 of 3 HCDR2s (i.e., differ by 2 amino acids) (see specification pg. 65 tables 4 and 5). In addition, all the disclosed Ta1501-1509 antibodies have more than 90% sequence identity between their respective VH regions and more than 96% identity between their respective VL domains. There is no evidence from the disclosure that anti-tau antibodies comprising i. CDRs with 85% homology to the instantly claimed CDRs, ii. either a VH or VL only antibody, iii. 85% homology to the instantly claimed VH or VL sequences, or iv. and antibody consisting of Seq ID Nos: 20 and 26 nor are there a representative number of disclosed species to support claiming a genus of i. antibodies that compete with an antibody comprising Seq ID NO: 20 and 26 or ii. that bind to phosphorylated Ser412, Thr414, nor Ser416.
It is also noted Applicant discloses the Tg mouse model used in the instant application, “studies using transgenic mice (Tg mice) with induced gene mutations such as P301L (a mutation from proline to leucine at the 301st amino acid residue of tau), and although such Tg mice serve as a gene mutation models for FTDP-17, a type of familial neurodegenerative disease, they do not represent most neurodegenerative diseases among tauopathies that are not accompanied by tau gene mutations, and particularly sporadic neurodegenerative diseases” (see specification pg. 6 para [0007]).
Regarding claim 15, the polyclonal antibody that binds to a phosphorylated serine at position 413 was engineered using a 7 contiguous amino acid sequence comprising amino acid residues 410-416 of Seq ID NO: 1 (see specification pg. 43 para [0054]). The monoclonal antibodies engineered to bind the same phosphorylated target as the polyclonal antibody were engineered using the synthetic peptide comprising Seq ID No: 35 comprising 25 amino acids with GlyCysSerGyl attached at the N-terminus (see specification pg. 46 line 3-9). Specificity of the identified antibodies was confirmed using the synthetic peptide Seq ID No: 33 comprising 17 amino acids (see specification pg. 49 para [0063]). It is noted the antibodies were made using linear peptides. This is not representative of the genus of antibodies that bind a specific epitope (i.e., amino acid residues 410-421 of Seq ID No:1 wherein Ser413 is phosphorylated). Anti-tau antibody Ta9 was engineered to recognize alternative phosphorylation sites on tau and therefore is not within the scope of the instant claim (see specification pg. 53 para [0072]).
State of the Art
Regarding prevention of all cognitive disorders, at the time of filing (i.e., 2013) clinical research over three decades had failed to delay the onset and progression of Alzheimer’s disease (AD) (see Selkoe, Dennis (2012) Preventing Alzheimer’s Disease. Science Vol. 337, Issue 6101, pg. 1488-1492, in particular abstract). Even as recently as 2024, research has yet to produce a preventative therapeutic for Alzheimer’s Disease (see Shi et al. (2024) Now and future: Strategies for diagnosis, prevention and therapies for Alzheimer’s disease, Science Bulletin 69, pgs. 3777-3784 in particular abstract, pg. 3777, 2nd col. 1st para). Therefore, an ordinary artisan would recognize a prophylactic agent for a cognitive disorder as well studied as Alzheimer’s disease has yet to be invented let alone for cognitive disorders genetically acquired. Colwell and Emborg disclose that as of 2025 “there are no effective treatments to prevent or slow down progressive tau accumulation” (see Colwell and Emborg, abstract).
Regarding variable CDRs, the state of the art teaches CDR sequences are the residues required for antigen binding and these sequences are highly variable in order to facilitate binding to a multitude of antigens (see Kapingidza et al. 2020. Antigen-Antibody Complexes. Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid, CH 19, pgs. 465-484, pg. 468, lines 1-4). Culang also teaches that CDRs are widely assumed to be responsible for antigen recognition (see Culang et al. The structural basis of antibody-antigen recognition. Front. In Immun. 2013. Vol. 4, Article 302, abstract). The state of the art also teaches the mutation effects at interfaces are often unpredictable and more often than not result in decreased binding affinity (see Clark et al. Influence of canonical structure determining residues on antibody affinity and stability. Journal of Structural Biology 185 (2014) 223–227, pg. 223, 2nd col. 1st full para). Amino acids within the CDR regions can have cooperative effects, for example, substitutions in the AQC2 antibody of M32L in LCDR1 when paired with a conservative substitution Y70F retains nearly wildtype affinity compared to pairing with V29I where nearly all binding affinity was lost, or a M32I substitution when parried with A25F resulted in no binding (see Clark, Table 1, pg. 223, 2nd col. 1st full para). Similarly, Brown demonstrated using the example of a T15 antiphosphocholine Ab where only 1 of 15 antibodies with a single mutation loss antigen binding while 16 of 31 antibodies with 2-4 mutations loss antigen binding (see Brown et al. as cited on the IDS dated 08/07/2025, pg. 3285, 1st col. 1st para, Table 1, pg. 3290 1st col. last para). Therefore, a person of ordinary skill in the art would understand that as little as two substitutions in the CDR regions of an antibody can result in a complete loss of binding for the target.
Regarding antibody fragments (e.g., single domain antibodies) encompassed by the present claims, the state of the art is such that conventional antibodies are exclusively expressed as parried heavy and light chains, and simply removing the VL domain in antibodies that were selected for binding in the presence of a cognate VL does not result in a functional, stable, domain antibody (see Rouet et al. Fully Human VH single domains that rival the stability and cleft recognition of camelid antibodies. The Journal of Biological Chemistry (2015) Vol. 290, No. 19, pgs. 11905-11917; see Holt et al. Domain antibodies: proteins for therapy. TRENDS in biotechnology (2003) Vol. 21, No. 11, pgs. 484-490, page 485, in particular). VH only antibody binding regions are found in camels, and screening can be performed to isolated camelid VHH sequences. However, conventional VH only domains are difficult to produce and problems relating to stability and poor biophysical properties hamper their isolation (see Rouet, page 11905). Thus, making a VH only domain antibody for binding and recognizing tau protein would be highly unpredictable.
Regarding antibodies that bind to a particular epitope of tau, in particular phosphorylated tau at positions 410-421 of Seq ID No: 1 the state of the art discloses 1 antibody named 961-S28T which recognizes amino acids 400-427 of tau in both unphosphorylated as well as phosphorylated forms (see Colwell and Emborg pg. 5 Table 2, last line). There are several antibodies known to bind tau wherein the epitope is currently unreported, has a particular epitope, conformations, or phosphorylation status; however, there does not appear to be more than a few antibodies targeting a particular area, conformation, or phosphorylation status of tau (see Colwell and Emborg pg. 5 Table 2, last line).
Therefore, an ordinary artisan at the time of the effective filing date would understand prophylactic agents for cognitive disorders has yet to be achieved in even the more widely studied disorders (e.g., AD). In addition, the residues with the CDR regions are either directly or indirectly integral to facilitating antigen binding and affinity as well as the importance framework regions in establishing and maintaining the antibody paratope. Small changes to the CDRs or framework regions can affect both the specificity of the target and the binding affinity.
Accordingly, in absence of substantive direction or guidance in the instant specification, the entire scope of experimentation required to develop the breadth of tau antibodies with i. at least one CDR, ii. at least one CDR with 85% homology, iii. either a VH or VL, iv. at least 85% homology to either a VH or VL sequence, v. specificity to one or more of phosphorylated Ser412, Thr414, and Ser416, and vi. competes with an antibody comprising Seq ID Nos: 20 and 26 is left to those skilled in the art. Given the resource intensive nature of the required experimentation, the skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
Claims 1, 2, 9, 13-15, and 20 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
Generic claims drawn to substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with a particular functional property or properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding, binding to a certain epitope), claiming antibodies solely with reference to said functional property, e.g., claiming the genus of all anti-tau antibody that compete with the anti-tau antibody with a VH consisting of Seq ID No:20 and a VL consisting of Seq ID No: 26 that also binds to tau that is phosphorylated at Ser413 of Seq ID No: 1, would not be sufficient to meet the written description requirement when the structures of antibodies having those properties have not been adequately described. See Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
In particular MPEP § 2163 instructs 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…See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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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) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").”
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by functional characteristic, such as its ability to bind tnfr1, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. In re Bell, 991 F.2d 781, 26 U.S.P.Q.2d 1529 (Fed. Cir. 1993). In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995).
Note well: even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
The genus of all anti-tau antibodies that compete with the anti-tau antibody with a VH consisting of Seq ID No:20 and a VL consisting of Seq ID No: 26 that also binds to tau that is phosphorylated at Ser413 of Seq ID No: 1 encompasses a vast diversity of molecules having distinct structural properties.
Claim 1 is drawn broadly to a therapeutic or prophylactic agent for cognitive disorders comprising an active ingredient wherein the active ingredient is an antibody capable of binding to tau protein phosphorylated at one position among positions 410 to 421 of Seq ID No: 1. The specification does not provide a limiting definition for prophylactic agent however does teach,
“The therapeutic agent or prophylactic agent for cognitive disorders of the invention may also be considered to have an effect of improving cognitive function or inhibiting loss or maintaining cognitive function in non-human animals” (see specification pg. 34 para [0041]), and
“The therapeutic or prophylactic agent for cognitive disorders according to the invention also encompasses the concept of a therapeutic agent or prophylactic agent comprising existing substances with effects of inhibiting developments of cognitive disorders” (see specification pgs. 49-50 para [0049]).
Prophylactic is defined as guarding from or preventing the occurrence of disease (see Definitions: Prophylactic, Merriam Webster, accessed online 15 September 2025) (see MPEP § 2111). The specification defines cognitive disorders in humans as “a condition of impairment in the intellectual function that has been developed or acquired, and it is considered a type of intellectual disturbance, and in a wider sense they are considered diseases exhibiting intellectual disturbance and/or memory impairment (see specification pg. 32, starting on line 15). Therefore, the language of claim 1 encompasses an agent capable of up to 100% prevention of any developed or acquired impairment in intellectual function (e.g., concussion). The antibody must bind tau protein that is phosphorylated on at least one amino acid residue among positions 410-421 of tau protein represented by Seq ID No: 1. It is noted the language of claim 1 does not limit the scope of the antibody to binding only a phosphorylated form of tau protein nor to the particular residues (i.e., epitope specific) in Seq ID No: 1; therefore, claim 1 encompasses antibodies capable of binding any location on any tau protein isoform comprising the particular residues instantly claimed (i.e., 410-421 of Seq ID No: 1) in either a phosphorylated or unphosphorylated form. It is noted the specification also teaches the particular residues instantly claimed (i.e., 410-421 of Seq ID No: 1) are present in multiple tau protein isoforms (e.g., Ser413 in Seq ID No: 1 (tau isoform 4R2N) corresponds to Ser384 in Seq ID No: 2 (tau isoform 4R1N)).
Claim 2 is additionally drawn to several embodiments of the claimed antibody all set forth in the alternative (i.e., “or”). For example, wherein the antibody which competes with an antibody including a VH consisting of Seq ID No: 20 and a VL consisting of Seq ID No: 26 (claim 2(iii)), iv. an antibody including a VH consisting of Seq ID No: 20 and a VL consisting of Seq ID No: 26 (claim 2(iv)), v. an antibody comprising less than 6 CDRs (e.g., one of, at least one of, at least 85% homology) (claim 2(vi)(vii)), or vi. an antibody comprising either a VH or VL or any combination of Seq ID Nos (claim 2(vii)). It is noted claim 2(iii) and (iv) are drawn to “an antibody including VH consisting of the amino acid sequence listed as Seq ID No: 20 and VL consisting of the amino acid sequence listed as Seq ID No: 26”. In so far as the language “antibody including” is intended to set forth a specific embodiment i.e., an antibody with a VH consisting of the amino acid sequence listed as Seq ID No: 20 and VL consisting of the amino acid sequence listed as Seq ID No: 26, the language of claim encompasses an antibody with only these two regions. The language of claim 2(vi) and (vii) are drawn to antibodies comprising as little as 1 CDR with 85% homology or antibodies with 85% homology to either a VH or VL which encompasses highly variable CDRs. Similarly, claim 2(iii) drawn antibodies that compete with a particular antibody encompasses a genus of anti-tau antibodies including human, humanized, or murine antibodies in any format (e.g., VHH, Fab, scFv, or full length), comprising any CDRs wherein the only two functional requirements are binding anywhere on tau when phosphorylated at any position between amino acids 410-421 of Seq ID No: 1 and either directly (e.g., binding the same epitope) or indirectly (e.g., binding affinity, steric hinderance) of a particular antibody.
Claim 15 is similar to claim 2 in that both claim are drawn to particular embodiments of the anti-tau antibody. However, claim 15 is also drawn to a monoclonal antibody that participates in antigen-antibody reaction with a peptide comprising (i.e., open language) a sequence of at least 8 contiguous amino acids from the sequence consisting of amino acid number 410-421 of Seq ID NO: 1 wherein the 4th serine (i.e., Ser413) in residues 410-421 is phosphorylated. Therefore, the language of claim 15 encompasses any monoclonal antibody that can bind to tau, given tau is a peptide that comprises amino acids 410-421 of Seq ID No: 1.
It is noted, the claims are drawn to a therapeutic agent wherein the therapeutic agent comprising an active ingredient wherein the active ingredient is an antibody (see claim 1 line 2). The specification does not provide a limiting definition for antibody. Pursuant to MPEP § 2111 the broadest reasonable interpretation of antibody at the time of filing includes single domain antibodies (i.e., VH only) (see Saerens et al. (2008) Single-domain antibodies as building blocks for novel therapeutics. Current Opinion in Pharmacology, 8: pgs. 600-608, in particular pg. 600, 2nd col. 3rd para).
Applicant’s results are also summarized above. Briefly, Applicants have identified 8 anti-tau (i.e., one polyclonal and 7 monoclonal) antibodies that specifically bind to a phosphorylated serine at position 413 of the long tau isoform (i.e., Seq ID No: 1) (see specification pg. 45 para [0059], pg. 50 para [0065], table 2). Specifically, the monoclonal antibodies comprise particular sets of VH and VL pairs (see specification pg. 65 tables 4-6). The anti-tau antibodies were engineered using either a synthetic peptide comprising 7 contiguous amino acid sequence comprising amino acid residues 410-416 of Seq ID NO: 1 (see specification pg. 43 para [0054]) or Seq ID No: 35 comprising 25 amino acids with GlyCysSerGyl attached at the N-terminus (see specification pg. 46 line 3-9). Specificity of the identified monoclonal antibodies was confirmed using the synthetic peptide Seq ID No: 33 comprising 17 amino acids (see specification pg. 49 para [0063]). Applicant has demonstrated both the polyclonal and a single monoclonal anti-tau antibody (i.e., Ta1505) improved memory impairment in Tg mice (see specification figures 8 and 12). There is no evidence from the disclosure that anti-tau antibodies comprising i. CDRs with 85% homology to the instantly claimed CDRs, ii. either a VH or VL, iii. 85% homology to the instantly claimed VH or VL sequences, or iv. and antibody consisting of Seq ID Nos: 20 and 26 nor are there a representative number of disclosed species to support claiming a genus of i. antibodies that compete with an antibody comprising Seq ID NO: 20 and 26 or ii. that bind to phosphorylated Ser412, Thr414, nor Ser416 were made.
As stated above, the CDRs and framework regions are integral to determining antigen binding, specificity and affinity (see above; Kapingidza pgs. 465-484, pg. 468, lines 1-4; see Culang abstract). Mutational effects on interfaces are often unpredictable(see Clark pg. 223, 2nd col. 1st full para). In addition, the state of the art discloses no known prophylactic agent capable of preventing a cognitive disorder or tauopathy (see Colwell and Emborg, abstract). As there is no art-recognized correlation between structure and function, it would be impossible for one of ordinary skill in the art to predict which CDRs, VH and/or VL sequences would result in a structure that binds to tau or competes with binding of the claimed antibody let alone those that would be prophylactic agents. Overall based on the disclosure, the state of the art at the time of filing, a skilled artesian would have recognized that the applicant was not in possession of the claimed invention.
Claim Rejections - 35 USC § 112
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 1, 2, 9, 13-15, and 20 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is drawn to an antibody that binds to tau that is phosphorylated “on at least one amino acid residue present among positions 410-421 of the tau protein represented by Seq ID No: 1”. The scope of the phosphorylation site is unclear. For example, is the claimed tau protein limited to the longest isoform of tau phosphorylated at a residue among 410-421 of Seq ID No: 1 (see specification pg. 3, para [0004]). Alternatively, the specification teaches amino acid sequence comprising amino acids 410-421 of Seq ID No: 1 is found in additional isoforms of tau; therefore, is the claim draw to phosphorylation of any residue in the subsequence 410-421 of Seq ID No: 1 in any isoform of tau comprising this subsequence. Alternatively, is the phosphorylated tau one wherein any amino acid found in the sub sequence (i.e., N, V, S, T, G, I, D, or M) in any position in tau is phosphorylated (e.g., the subsequence comprises S; therefore, phosphorylated serine 205 is within the scope of the claim).
Claim 2 the following is unclear:
The scope of “phosphorylated tau protein characteristic of cognitive disorders” (claim 2(i)). It is unclear when is a phosphorylated tau protein characteristic of a cognitive disorder and when is it not. For example, is a phosphorylated tau present in both human and subjects with cognitive disorders a “tau protein characteristic of a cognitive disorder”. Alternatively, is claim limited to phosphorylated tau only found in subjects with a cognitive disorder.
The scope of the one or more sites of phosphorylation are unclear (claim 2(ii)), given these positions are drawn to Seq ID No: 1 or alternatively are these positions drawn to the subsequence as they appear in alternative tau isoforms,
The scope of the competing antibody (claim 2(iii)). For example, is the claim drawn to an antibody that binds in competition with an antibody including the instantly claimed structure but is not limited to that structure (i.e., is “including” synonymous with “for example”) or alternatively is the competing antibody one that comprises Seq ID Nos: 20 and 26,
Similarly to above, the scope of the antibody (claim 2(iv)). For example, is the claim drawn to antibody including the instantly claimed structure but not limited to said structure, or alternatively, the claim is limited to an antibody comprising Seq ID Nos: 20 and 26,
Similarly to above, the scope of the phosphorylated tau. For example is the tau limited to the longest isoform of tau phosphorylated at position 413, or alternatively, any tau isoform comprising the subsequence wherein the 4th serine (i.e., Ser413) is phosphorylated, and
The scope of the antibody structure (claim 2(vi)). The claim recites:
“the antibody is an antibody comprising a CDR sequence on the H chain represented by Seq ID Nos: 7-13, a CDR sequence on the H chain represented by at least one of Seq ID Nos: 7-13 or a CDR sequence on the H chain having at least 85% homology with at least one CDR sequence on the H chain represented by Seq ID Nos: 7-13”. It is unclear if this is three embodiments each represented by the underline, bold, or italicized text, or alternatively 2 embodiments wherein the first embodiment is underlined and the second embodiment is the bold and italicized text. If it is Applicant’s intend to set forth three embodiments it is unclear how the scope of the underlined text differs from the bold text, given both are drawn to a single CDR selected from Seq ID Nos: 7-13. Likewise claim 2(vi) also recites, “a CDR sequence on the L chain represented by Seq ID Nos: 14-17, a CDR sequence on the L chain represented by at least one of Seq ID Nos: 14-17 or a CDR sequence on the L chain having at least 85% homology with at least one CDR sequence on the H chain represented by Seq ID Nos: 14-17”. For the reasons set forth above regarding the H chain the scope of L chain CDR is also unclear.
In addition, claim 2(vi) recites the limitation "the H chain" 4 times in lines 1-4 and “the L chain” 4 times in lines 5-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 is drawn to “a monoclonal antibody that participates in antigen-antibody reaction with a peptide comprising a sequence of at least 8 contiguous amino acids” in lines 1-2. The scope of the monoclonal antibody is unclear. The specification defines “participates in an antigen-antibody reaction” as binding with tau protein that has been phosphorylated on at least one amino acid residue corresponding to positions 410-421 of Seq ID No: 1 (see specification pg. 22 para [0024]) yet the claim also recites this limitation regarding an 8 amino acid peptide. Therefore, it is unclear if the antibody binds specifically to the “at least 8 contiguous amino acids” or alternatively to a tau protein comprising at least 8 contiguous amino acids. Claim 15 is also unclear for the same reasons claim 1 (set forth above) is also unclear regarding the scope of phosphorylated residue among residues 410-421 of Seq ID No: 1. In addition, claim 15(i)-(iv) are unclear for the same reasons set forth above for claim 2(iii), (iv), (vi), and (vii).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, and 13-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) “an antibody that participates in antigen-antibody reaction with tau protein that has been phosphorylated on at least one amino acid residue present among positions 410 to 421 of the tau protein represented by Seq ID No: 1” (see claim 1). It is noted the specification teaches the amino acid residues 410-421 of Seq ID No: 1 are found in several isoforms of tau; however, at different positions in each tau isoform (see specification pg. 3 para [0004]). For example, Ser413 of Seq ID No: 1 is Ser384 is the 4R1N tau isoform or Ser355 of the 4R0N tau isoform (see specification pg. 3 para [0004]). Furthermore, the language of claim 1 broadly encompasses any anti-tau antibody capable of binding any portion of tau wherein the tau protein is phosphorylated at Ser413. The language of claim 1 does not limit the claimed antibody to binding the instantly claimed residues. Using the Alice test:
Step 1: Yes, the claim is drawn to a composition or product.
Step 2A: Yes, the product is to a product of nature.
It was known at the time of filing that naturally occurring antibodies that bind pathological phosphorylated tau exist in the sera from Alzheimer’s disease subjects (see Rosenmann et al. (2006) Detection of circulating antibodies against tau protein in its unphosphorylated and in its neurofibrillary tangles-related phosphorylated state in Alzheimer’s disease and healthy subjects. Neuroscience Letters, Vol. 410, Iss. 2, pgs. 90-93, in particular abstract, pg. 91, 2nd col. 4th para). Rosenmann discloses antibodies that bind pathological phosphorylated tau were identified using ELISA and a phosphorylated tau peptide at positions 202 and 205 (see Rosenmann pg. 91, 1st col. 2nd full para). Imahori discloses the neurofibrillary tangles (NFT) are formed from abnormally paired helical filaments (PHFs) that consist mainly of hyperphosphorylated tau (see Imahori et al. (1998) Possible role of tau protein kinases in pathogenesis of Alzheimer’s disease. Neurobiology of Aging, Vol. 19, No. 1S, pgs. S93-98, in particular pg. S93, 1st col. 1-2nd para). In addition, of the 10 major phosphorylation sites Ser202, Thr205, and Ser413 are listed (see Imahori pg. S94, 1st col. 1st full para and para spanning col. 1-2, Table 1).
Step 2B: No. This judicial exception is not integrated into a practical application (e.g., administration) because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite only a functional property and no corresponding structure (e.g. binding phosphorylated tau (see claim 1), binding to phosphorylated tau characteristic of cognitive disorder (see claim 2(i)).
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 2, and 13-15 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Torreilles (Torreilles et al. (2000) Binding specificity of monoclonal antibody AD2: influence of the phosphorylation state of tau. Molecular Brain Research, Vol 78, Iss. 1-2, pgs. 181-185) as evidenced by Mukrasch (see Mukrasch et al. Structural polymorphism of 441-residue tau at single residue resolution. PLoS Biol. 2009 Feb 17;7(2):e34).
Torreilles discloses antibody Tau2 binds to rtau phosphorylated with rat brain extract, with GSK-3β, or with GSK-3β/heparin (see Torreilles pg. 182, 2nd col. 1st full para, figure 1). GSK-3β is the only kinase known to phosphorylate serine 413 of the longest isoform of tau (i.e., instant Seq ID No: 1) as evidenced by Imahori (see Imahori pg. S93, 2nd col., last para-pg. S94, 1st col. 1st full para). Therefore, Torreilles discloses an anti-tau antibody that binds to tau phosphorylated at position 413 of Seq ID No: 1. It is noted the rtau taught by Torreilles comprises htau40 with a polyhistidine tag (see Torreilles pg. 181, 2nd col. 1st full para). It is noted htau40 comprises the longest isoform of tau in the human CNS (411 residues) and is identical to instant Seq ID No: 1 as evidenced by Mukrasch (see Mukrasch figure 1). This is pertinent to instant claims 1, claim 2(ii) and (v), and claim 15.
Claims 13 and 14 are drawn to wherein the cognitive disorder is further limited to particular disorders (e.g., tauopathy, Alzheimer’s Disease) and do not further limit the structure of the antibody. Therefore, anticipation of the antibody anticipates the intended use of the antibody.
Claims 1, 2, 9, 13-15, and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over WO2010/144711 A1 (referred to herein as Sigurdsson, as cited on the IDS filed 7 August 2025).
As stated above, the language of claim 1 is drawn to an antibody that must bind tau protein that is phosphorylated on at least one amino acid residue among positions 410-421 of tau protein represented by Seq ID No: 1. The language of claim 1 does not limit the scope of the antibody to binding only a phosphorylated form of tau protein nor to the particular residues (i.e., epitope specific) in Seq ID No: 1; therefore, claim 1 encompasses antibodies capable of binding any location on any tau protein isoform comprising the particular residues instantly claimed (i.e., 410-421 of Seq ID No: 1) in either a phosphorylated or unphosphorylated form. Similarly, claim 15 is also drawn to a monoclonal antibody that participates in antigen-antibody reaction with a peptide comprising (i.e., open language) a sequence of at least 8 contiguous amino acids from the sequence consisting of amino acid number 410-421 of Seq ID NO: 1 wherein the 4th serine in residues 410-421 is phosphorylated. Therefore, the language of claim 15 encompasses any monoclonal antibody that can bind to tau, given tau is a peptide that comprises amino acids 410-421 of Seq ID No: 1.
Sigurdsson discloses antibodies that preferentially recognize phosphorylated pathological epitopes of tau protein involved in promoting neuronal toxicity and/or seeding of tau aggregation such as Seq ID Nos: 52, 74, 75, and 101 (see Sigurdsson pg. 20 Table 2, pg. 25 para [0052, 0054]). Note the following:
Seq ID No: 52 comprises tau amino acids 398-416 and specifies phosphorylated S314 (instant claim 1),
Seq ID No: 74 comprises tau amino acids 390-420 and specifies phosphorylated S314 (instant claims 1 and 15),
Seq ID No: 75 comprises tau amino acids 411-441 and specifies phosphorylated S314 (instant claims 1 and 15), and
Seq ID NO: 101 comprises tau amino acids 407-421 and specifies phosphorylated S314 (see Sigurdsson pg. 17 para [0041, pg. 20 Table 2; see instant claims 1 and 15).
Sigurdsson discloses an antibody that binds to D421 of a truncated tau protein engineered using Seq ID No: 101 (see Sigurdsson pg. 26 para [0054]). It is noted Seq ID No: 101 comprises all of the amino acid residues instantly claimed (i.e., amino acids 410-421 of instant Seq ID NO: 1). Sigurdsson also discloses wherein the antibody is humanized for therapeutic purposes to reduced antigenicity and human anti-mouse antibody response (see Sigurdsson pg. 27 para [0057], pg. 29 para [0062]). This is pertinent to instant claims 1, 2, 9, 15, and 20.
Claims 13 and 14 are drawn to wherein the cognitive disorder is further limited to particular disorders (e.g., tauopathy, Alzheimer’s Disease) and do not further limit the structure of the antibody. Therefore, anticipation of the antibody anticipates the intended use of the antibody. Although Sigurdsson discloses the antibodies are for treating, preventing and diagnosing Alzheimer’s Disease (see Sigurdsson abstract, pg. 25 para [0052], pg. 36 para [0082]).
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 (i.e., changing from AIA to pre-AIA ) 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 9 and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Torreilles and WO2010/144711 A1 (referred to herein as Sigurdsson, as cited on the IDS filed 7 August 2025).
The reasons claims 1 and 15 are anticipated by Torreilles are set forth above.
Sigurdsson discloses antibodies that preferentially recognize phosphorylated pathological epitopes of tau protein involved in promoting neuronal toxicity and/or seeding of tau aggregation such as Seq ID Nos: 74, 75, and 101 (see Sigurdsson pg. 20 Table 2, pg. 25 para [0052, 0054]). It is noted Sigurdsson Seq ID No: 74 comprises tau amino acids 390-420, Seq ID No: 75 comprises tau amino acids 411-441, and Seq ID NO: 101 comprises tau amino acids 407-421 (see Sigurdsson pg. 20 Table 2). Both Seq ID Nos: 74 and 75 comprises pseudo-phosphorylated tau at Ser413 (see pg. 17 para [0041], pg. 20 Table 2). Sigurdsson discloses an antibody that binds to D421 of a truncated tau protein engineered using Seq ID No: 101 (see Sigurdsson pg. 26 para [0054]). It is noted Seq ID No: 101 comprises all of the amino acid residues instantly claimed (i.e., amino acids 410-421 of instant Seq ID NO: 1). Sigurdsson also discloses wherein the antibody is humanized for therapeutic purposed due to reduced antigenicity and human anti-mouse antibody response (see Sigurdsson pg. 27 para [0057], pg. 29 para [0062]).
Therefore, an ordinary artisan would humanize the Tau2 antibody taught by Torreilles in order to reduce antigenicity and human anti-mouse antibody response as taught by Sigurdsson.
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 1, 2, 9, 13-15, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 6, and 7 of U.S. Patent No. 10,556,950 B2 (referred to herein as ‘950). Although the claims at issue are not identical, they are not patentably distinct from each other.
The ‘950 patent claims an anti-pSer413 tau antibody comprising i. a VH comprising any one of Seq ID Nos: 20 (91.1%), 22 (90.5%), 24 (91.6%), 26 (92.2%), 28 (91%), 116 (89.1%), and 117 (91.6%) and ii. a VL comprising Seq ID No: 34 (96.7%), 42 (96.7%) (see ‘950 claim 1, claim 2(i), (ii), (iii), (v), (vi), and (vii), claim 15(i), (iii), and (iv)). It is noted the percentages in “()” is the percent sequence identity to the instantly elected Seq ID Nos: 20 and 26, respectively. In addition, the ‘950 patent claims a method of treating a tauopathy, in particular all of the instantly claimed diseases (see ‘950 claims 6 and 7; see instant claims 13 and 14). The claimed antibodies are humanized (see ‘950 col. 45, 1st para; see instant claims 9 and 20). Therefore, the ‘950 patent anticipates instant claims 1, 2, 9, 13-15, and 20.
Claims 1, 2, 9, 13-15, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 14, 16 and 17 of U.S. Patent No. 10,894,829 B2 (referred to herein as ‘829). Although the claims at issue are not identical, they are not patentably distinct from each other.
The ‘829 patent claims a humanized antigen binding fragment (instant claims 9 and 20) that specifically binds to either tau or a tau peptide that is phosphorylated at Ser413 of Seq ID No: 1 (see ‘829 claim 13; see instant claim 1). It is noted Seq ID No: 1 of the ‘829 patent is identical to the instantly claimed Seq ID No: 1. The claimed antibody comprises HCDRs 1 and 2 comprising Seq ID Nos: 10 and 12 and LCRs1-3 comprising Seq ID Nos: 14, 16, and 17(see ‘829 claim 14; see instant claim 2(i), (ii), (iii), (v), and (vi), claim 15(i) and (iii)). It is noted Seq ID No: 10 is identical to the instantly claimed Seq ID No: 8 (elected), Seq ID No: 12 has 94.7% identity to the instantly claimed Seq ID No: 9 (elected), Seq ID No: 14 has 93.75% identity to instantly claimed Seq ID No: 14 (elected), and Seq ID Nos: 16 and 17 (both elected) are identical to the instantly claimed Seq ID Nos: 16 and 17. The ’829 patent also claims a method of treating a tauopathy by administering the humanized antibody and wherein the tauopathy is specifically selected from a list comprising all the instantly claimed tauopathies (see ‘829 claims 16 and 17; see instant claims 13 and 14).
Claims 1, 2, 9, 13-15, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 of U.S. Patent No. 11,739,143 B2 (referred to herein as ‘143). Although the claims at issue are not identical, they are not patentably distinct from each other.
The ‘143 patent claims a humanized antibody or antigen binding fragment (instant claims 9 and 20) that specifically binds to phosphorylated tau at position Ser413 of Seq ID No: 1 (see ‘143 claim 9; see instant claim 1). It is noted Seq ID No: 1 of the ‘143 patent is identical to the instantly claimed Seq ID No: 1. The claimed antibody comprises HCDRs1-3 from a VH domain comprising Seq ID No: 116 and LCRs1-3 from a VL comprising any one of Seq ID Nos: 103-114 (see ‘143 claim 9; see instant claim 2(i), (ii), (iii), (v), (vi), and (vii), claim 15(i), (iii), and (iv)). It is noted Seq ID No: 116 has 89.1% sequence identity to the instantly claimed Seq ID No: 20 (elected), in particular, identical HCDRs 1-3 as instantly claimed Seq ID Nos: 8, 9, and 13 save for a single position in HCDR2, while any of Seq ID Nos: 103-114 have more than 90% sequence identity to the instantly claimed Seq ID No: 26. The ’143 patent also claims a method of treating a tauopathy by administering the humanized antibody and wherein the tauopathy is specifically selected from a list comprising all the instantly claimed tauopathies (see ‘143 claims 11 and 12; see instant claims 13 and 14).
Conclusion
No claim allowed.
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/H.A.P./ Examiner, Art Unit 1644
/AMY E JUEDES/ Primary Examiner, Art Unit 1644
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