DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of the species of “(iii)” relating to a tau (τ) level in the reply filed on June 5, 2026 is acknowledged.
Claims 2-11, 19, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 5, 2026.
Claim Objections
Claim 16 is objected to because of the following informalities: it appears an “is” is appropriate after “increase” in line 2. Also there are double closing parentheses in line 3. Appropriate correction is required.
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 and 12-18 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.
Claims 1, 12, and 13, contain the phrases "(e.g., a rate of increase)", “(e.g., in a bodily fluid)”, and “(e.g., increase)” which render the claims indefinite because it is unclear whether the limitations following the “e.g.,” are part of the claimed invention. See MPEP § 2173.05(d). None of the dependent claims resolves this issue and therefore they are also rejected on this ground.
Claim 17 recites “wherein said corresponding reference is a corresponding pretreatment level in said bodily fluid”. Claim 12 from which it depends recites “a corresponding reference over the same duration”. The “pretreatment level” means the baseline level existing at a single point in time prior to starting the administration of the p75NTR receptor modulator. Therefore “over the same duration” is not applicable as does “a change …or a rate of change …in a tau (τ) level…over a duration” in claim 12.
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 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 12-15, 17, and 18 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Longo studied the effects of p75 neurotrophin receptor (p75NTR) ligands LM11A-31 and LM11A-24 on tau pathology and neuroinflammation (title; abstract; p.460-61 AβPPL/S mice, p.462 Quantitation of tau pathology in the cortex). Longo found that over 3 months LM11A-31 reduced tau hyperphosphorylation in AβPPL/S mice compared to vehicle-treated AβPPL/S mice (p.466-67 p75NTR ligand reduces tau hyperphosphorylation in AβPPL/S mice). “Treatment with LM11A-31 significantly reduced excessive p-tau in AβPPL/S mice by 59% for regions of combined dystrophic neurite clusters and non-cluster/cell bodies (Fig. 3C, left graph), by 43% for non-cluster/cell bodies (Fig. 3C, middle graph), and by 45% for dystrophic neurite clusters (Fig. 3C, right graph), while vehicle had no effect.” (p.467 Left col.) LM11A-24 caused a more modest reduction in p-tau accumulation only in non-cluster/cell body regions at a 100 mg/kg dose (p.467). The p-tau would be lowered in body fluids such as those in claim 15.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1 and 12-18 are rejected under 35 U.S.C. 103 as being unpatentable over Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Longo does not refer to the annual percent change (APC) in a tau (τ) level in claim 16.
However the skilled person could reasonably expect a lowered estimated rate of increase in hyperphosphorylated tau over a year based on the dramatical reduction in the 3-month data in Longo. Moreover a clause that “simply expresses the intended result of a process step positively recited” in a method claim is not given weight. MPEP §2111.04(I)(citations omitted). Here claim 16 recites a result “provides a tau (τ) level…”, which is not a step that is performed actively. Rather it would occur as a result of the administering step in claim 12. Thus the clause raises a question as to the limiting effect of the claim language. Such a clause “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited”, as in the instant claim. MPEP § 2111.04 (citations omitted).
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 and 12-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10273219 in view of Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets are drawn to the p75NTR ligand. The ‘219 patent claims recite crystalline forms of LM11A-31. The present claims recite a method for modulating tau (τ) as a neurodegeneration biomarker by administering an effective amount of a p75NTR receptor modulator. Longo teaches LM11A-31, a p75NTR receptor modulator, reduces tau hyperphosphorylation. Therefore the skilled person would have been motivated to use the crystalline forms LM11A-31 to practice reduce hyperphosphorylated tau (τ) levels.
Claims 1 and 12-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11225467 in view of Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets are drawn to a method comprising administering a p75NTR ligand. The present claims recite a method for modulating a neurodegeration biomarker, tau (τ) level, by administering an effective amount of a p75NTR receptor modulator. The ‘467 patent claims a method of treating Alzheimer’s disease by administering a crystalline form of LM11A-31. Longo teaches LM11A-31 reduces tau hyperphosphorylation, which is a biomarker in Alzheimer’s disease. Therefore the skilled person would have been motivated to use the crystalline forms of the ‘467 patent to modulate tau (τ) levels.
Claims 1 and 12-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9271986 in view of Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets are drawn to the p75NTR ligand. The ‘986 patent claims recite crystalline forms of LM11A-31 sulfate salt. The present claims recite a method for modulating tau (τ) as a neurodegeneration biomarker by administering an effective amount of a p75NTR receptor modulator. Longo teaches LM11A-31, a p75NTR receptor modulator, reduces tau hyperphosphorylation. Therefore the skilled person would have been motivated to use the crystalline forms LM11A-31 sulfate salt to practice reduce hyperphosphorylated tau (τ) levels.
Claims 1 and 12-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10532988 in view of Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets are drawn to the p75NTR ligand. The ‘988 patent claims recite crystalline forms of LM11A-31 sulfate salt. The present claims recite a method for modulating tau (τ) as a neurodegeneration biomarker by administering an effective amount of a p75NTR receptor modulator. Longo teaches LM11A-31, a p75NTR receptor modulator, reduces tau hyperphosphorylation. Therefore the skilled person would have been motivated to use the crystalline forms LM11A-31 sulfate salt to practice reduce hyperphosphorylated tau (τ) levels.
Claims 1 and 12-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9464066 in view of Longo (Longo, F.M., et al., Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice, Journal of Alzheimer’s Disease 42 (2014) 459–483).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets are drawn to the p75NTR ligand. The ‘066 patent claims recite deuterated forms of LM11A-31 and method of treating a neurodegenerative disease by administering the same. The present claims recite a method for modulating tau (τ) as a neurodegeneration biomarker by administering an effective amount of a p75NTR receptor modulator. Longo teaches LM11A-31, a p75NTR receptor modulator, reduces tau hyperphosphorylation involved in Alzheimer’s disease. Therefore the skilled person would have been motivated to use the deuterated forms of LM11A-31 sulfate salt to practice reduce hyperphosphorylated tau (τ) levels.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614
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