Detailed Action
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 Claims 10, 11, and 21-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group (i.e., peptide), there being no allowable generic or linking claim.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 26-35 are newly added in the Response to Non-Final received 1 April 2026 (referred to herein as Remarks). Claims 1, 2, 9, 14, 15, 20, and 26-35 are currently under consideration.
Specification
In view of Applicant amending the specification to remove reference to “http:” the objection to the specification is hereby withdrawn.
Claim Objections
Applicant is advised that should claims 20 and 28 be found allowable, claims 32 and 34 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Withdrawn Rejections
In view of Applicant amending claims 1, 2, and 15 the 35 USC 112(a) rejections (i.e., scope of enablement and written description) of claims 1, 2, 9, 13-15, and 20 are hereby withdrawn. It is noted new rejections under 35 USC 112(a) necessitated by amendment is below.
In view of Applicant amending claims 2 and 15 the 35 USC 112(b) rejection is hereby withdrawn. It is noted new rejections under 35 USC 112(a) necessitated by amendment is below.
In view of Applicant amending claims 1 and 15 to recite specific CDRs the 35 USC 101 and 35 USC 102, and 35 USC 103 rejections are hereby withdrawn.
Maintained Rejections
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, 14, 15, 20, and 26-35 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.
It is noted, the rejection has been amended to reflect new claim language but the underlying basis for the rejection remains the same as in the Non-final mailed 1 October 2025. Claims 1 and 15 are drawn to an antibody that binds a tau protein “phosphorylated at Ser413 of Seq ID No: 1 with a higher affinity than to a tau protein not phosphorylated at Ser413 of 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 (i.e., Seq ID No: 1) or alternatively, the specification teaches alternative isoforms of tau comprise the same phosphorylation site with a different position number. Therefore, is the claim drawn to binding the longest isoform of tau with phosphorylated Ser413 or any isoform of tau comprising the same phosphorylation site at a different position number.
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, 20, 26, 27, and 29-35 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, as cited on the PTO-892 mailed 10/01/2025, pg. 1 patent A). 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%), 24 (91.6%), 26 (92.2%), and ii. a VL comprising Seq ID No: 42 (96.7%) (see ‘950 claims 1(a), 2(a), 15(a), 26(c), 27(c), 29(a), 30(c), 31(c)). It is noted the ‘950 claims antibodies with 100% sequence identity to instantly elected Seq ID Nos: 8, 9, 13, 14, 16, and 17 and the percentages in “()” are 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 14 and 35). The claimed antibodies are humanized (see ‘950 col. 45, 1st para; see instant claims 9 and 20, and 32-34). Therefore, the ‘950 patent anticipates instant claims 1, 2, 9, 13-15, 20, 26, 27, and 29-35.
Claims 1, 2, 9, 14, 15, 20, 28, 29, and 32-35 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, as cited on the PTO-892 mailed 10/01/2025, pg. 1 patent B). 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, 20, and 32-34) that specifically binds to either tau or a tau peptide that is phosphorylated at Ser413 of Seq ID No: 1 compared to an unphosphorylated tau peptide (see ‘829 claim 13 and 15; see instant claims 1, 15, 16, 27, and 29-31). 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 1-3 comprising Seq ID Nos: 10, 11, and 13 and LCDRs 1-3 comprising Seq ID Nos: 15-17 (see ‘829 patent claim 14(C); see instant claims 1(a), 2(a), 15(a), and 29(a)). 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 9, 14 and 32-35). This is pertinent to instant claims 1, 2, 9, 14, 15, 20, 28, 29, and 32-35.
Claims 1, 2, 9, 13-15, 20, 26, 27, and 29-35 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, as cited on the PTO-892 mailed 10/01/2025, pg. 1 patent C). 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, 20, and 32-34) that specifically binds to phosphorylated tau at position Ser413 of Seq ID No: 1 (see ‘143 claim 9; see instant claim 1, 15, 16, 27, and 29-31). 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 claims 1(a), 2(a), 15(a), 26(c), 27(c), 29(a), 30(c), 31(c)). 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 (i.e., 90% sequence identity), while any of Seq ID Nos: 113 has more than 90% sequence identity to the instantly claimed Seq ID No: 26 and identical LCDRs 1-3 as instantly elected (i.e., instant Seq ID Nos: 14, 16, and 17). 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 14 and 35).
The following rejections are necessitated by amendment.
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, 9, 14, 15, 20, 26, 30, and 32 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 particular sets of CDRs (see claims 2 and 29), does not reasonably provide enablement for 90% sequence identity to a CDR (see instant claims 1 and 15). 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, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
Claims 1 and 15 are drawn to antibodies with 90% sequence identity to individual CDRs. The language of the claims encompasses a genus of antibodies with at least one substitution at any position in any CDR.
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 as cited on the PTO-892 mailed 10/01/2025 pg. 2, reference W; see Kapingidza pg. 468, lines 1-4). Culang also teaches that CDRs are widely assumed to be responsible for antigen recognition (see Culang as cited on the PTO-892 mailed 10/01/2025 pg. 1, reference X; see Culang 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 as cited on the PTO-892 mailed 10/01/2025 pg. 1, reference V; see Clark 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. Tolerance to Single, but Not Multiple, Amino Acid Replacements in Antibody VH, CDR2. J Immunol (1996) 156 (9): 3285–3291. 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.
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 90% homology to the instantly claimed CDRs, at each and every position of each and every CDR bind preferentially to a Ser413 phosphorylated tau.
Accordingly, in absence of substantive direction or guidance in the instant specification, the scope of experimentation required to develop antibodies with 90% sequence identity across any CDR at any position and identify those that retain preferential binding to phosphorylated Ser413 of tau is left to those skilled in the art. Given the unpredictability in altering a single amino acid or combinations thereof, the present claims and disclosure amount to an invitation to the skilled artisan to develop such embodiments. The skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
Claims 1, 9, 14, 15, 20, 26, 30, and 32 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.
Claims 1 and 15 are drawn to antibodies with 90% sequence identity to individual CDRs. The language of the claims encompasses a genus of antibodies with at least one substitution at any position in any CDR.
As state above Applicants have disclosed anti-Ser413 tau antibodies with highly homologous CDRs, VH, and VL regions. There is no evidence from the disclosure that anti-tau antibodies comprising i. CDRs with 90% homology to the instantly claimed CDRs, at each and every position of each and every CDR bind preferentially to a Ser413 phosphorylated tau nor are there a representative number of species. As stated above, the CDRs are integral for antigen binding (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).
Therefore, a person of ordinary skill in the art at the time of filling would understand residues within the CDRs are integral to antigen binding or maintaining the structure of the region that binds to the antigen and substitutions in these regions would affect one or both these attributes. 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 or subsequent VH and VL sequences would result in a structure that preferentially binds phosphorylated Ser413 of tau. 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 at the time of filing.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 14 and 35 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 14 and 35 are drawn to a therapeutic agent or prophylactic agent for cognitive disorder (see lines 1-2); however, claims 1 and 2 are drawn to therapeutic agents for treating a tauopathy (see claim 1 lines 1-2). Therefore, claims 14 and 35 expand the scope of the claimed structure and the intended use of the structure. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claim allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/H.A.P./Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644
Prosecution Insights