Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
1. Claims 1-85 are the original claims filed on 10/3/2022. In the preliminary amendment of 6/7/2023, claims 3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, 69, and 70 are amended, and claims 4, 7-16, 18, 20-21, 24, 27-31, 33, 35, 38, 41-43, 45, 47, 49-50, 53, 56, 60-64, 66-68, and 71-85 are canceled. In the Response of 11/6/2025, claims 2, 3, 5, 6, 17, 22, 23, 26, 34, 36, 37, 39, 44, 46, 48, 51, 52, 54, 55, 57-59, and 69 are amended, claims 1, 19, and 25 are canceled, and new claim 86 is added. Claims 2-3, 5-6, 17, 22-23, 26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, 69-70 and 86 are all the claims.
The amendment of the claims raises new grounds for rejection. The Office Action is final.
Priority
2. USAN 17/916,728, filed 10/03/2022, is a National Stage entry of PCT/US2021/025626, International Filing Date: 04/02/2021, PCT/US2021/ 025626 Claims Priority from Provisional Application 63/005,130, filed 04/03/2020, PCT/US2021/025626 Claims Priority from Provisional Application 63/079,810, filed 09/17/2020.
Information Disclosure Statement
3. As of 12/23/2025, a total of three (3) IDS are filed: 2/14/2023; 6/7/2023; and 11/6/2025. The corresponding initialed and dated 1449 form is considered and of record. The submissions are in compliance with the provisions of 37 CFR 1.97.
Withdrawal of Objections
Specification
4. The objection to the abstract of the disclosure because the terms “e.g.,” and “etc.,” are indefinite is withdrawn. The corrected abstract deletes those terms.
5. The objection to the disclosure because of informalities is withdrawn. Both clean and marked-up copies of the specification are filed.
a) The specification is amended to rectify the improper use of the term Sepharose, UniProt, Tween, Tris, Triton, NCBI, Vizamyl, Amyvid, Neuraceq, Sector, FlowJo, Cignal, BioTek, MMSE, DNASTAR, which is a trade name or a mark used in commerce.
b) The specification is amended to rectify the typographical error for omission of a symbol at:
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Claim Objections
6. The objection to Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 because of informalities is moot for the canceled claims and withdrawn for the pending claims.
Claim 2 is amended to recite “the human individual in need thereof.”
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
7. The rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot for the canceled claims and withdrawn for the pending claims.
a) Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 are amended to delete the term “about” in defining the claimed ranges.
b) Claim 25 is canceled.
Claim Rejections - 35 USC § 112(a)
Enablement
8. The rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 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 enablement requirement is moot for the canceled claims and withdrawn for the pending claims. The pending claims are amended to delete the phrase “and/or delaying the progression.”
Rejections Maintained
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
9. The rejection Claim 2 under 35 U.S.C. 103 as being obvious over Schwabe et al (USPN 10676525 or USPN 11634489) is maintained.
Applicants allege the cited references do not disclose administering an anti-TREM2 antibody as recited in claim 2 to a human specifically at a dose of at least 15 mg/kg intravenously, or that the anti-TREM2 antibody comprises the HVR sequences as recited in claim 2, or the disease or injury is selected from the group consisting of: frontotemporal dementia, Alzheimer's disease, memory loss, a demyelination disorder, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).
Response to Arguments
The teachings of 10676525/11634489 are according to known methods, use of identical reagents, and the practice of conventional steps with a reasonable expectation of success and predictable results.
Under the KSR decision, the cited references of art are not required to “explicitly teach or suggest” all of the steps or elements. The Supreme Court has determined in KSR International Co. v. Teleflex, Inc., 550 U.S._, 82, USPQ2d 1385 (2007), that “a person of ordinary skill attempting to solve a problem will” not “ be led only to those elements of prior art designed to solve the same problem………” (KSR, 550 U.S. at_, 82 USPQ2d at 1397). In addition, the court found that “When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variant, 35 USC 103 likely bars its patentability” (KSR, 550 U.S. at_, 82 USPQ2d at 1396). Further the court found that the Federal Circuit has erred in applying the teaching-suggestion-motivation test in an overly rigid and formalistic way, in particular by concluding “that a patent claim cannot be proved obvious merely by showing that the combination of elements was 'obvious to try'” (KSR, 550 U.S. at_, 82 USPQ2d at 1397) and has further determined that “…….[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results” (KSR, 550 U.S. at_, 82 USPQ2d at 1395). The court further found that “……… the conclusion that when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious” (KSR, 550 U.S. at_, 82 USPQ2d at 1395-1396). Thus, when considering obviousness of a combination of known elements, the operative question is “whether the improvement is more than the predictable use of prior art elements according to their established functions” ((KSR, 550 U.S. at_, 82 USPQ2d at 1396).
Applicants have not demonstrated the instant claimed method is an improvement or unexpected result over the reference disclosures of 10676525 or 11634489, each of which provide the technical details for practicing the method steps and the motivation to practice a clinical method with intended therapeutic outputs for what is otherwise disclosed in each reference.
10676525/11634489: as regards the VHCDR1-3/ VLCDR1-3 of the AL2p-58 clone
FIG. 8A and FIG. 8B depict increased viability (as increase in cellular ATP) after stimulation of primary human macrophages (FIG. 8A) or human primary dendritic cells (FIG. 8B) from one donor with plate bound TREM2 antibodies vs. control IgG for 48 hours. FIG. 8C, FIG. 8D, FIG. 8E, and FIG. 8F depict increased viability (as increase in cellular ATP) after stimulation of primary human dendritic cells of two donors (FIG. 8C and FIG. 8D) or human primary macrophages of two donors (FIG. 8E and FIG. 8F) with soluble AL2p-58 huIgG1 vs. control human IgG1 for 48 hours.
10676525/11634489: as regards human individual and the iv route of administration
An “individual” for purposes of treatment, prevention, or reduction of risk refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sport, or pet animals, such as dogs, horses, rabbits, cattle, pigs, hamsters, gerbils, mice, ferrets, rats, cats, and the like. In some embodiments, the individual is human.
Pharmaceutical compositions of the present disclosure containing an anti-TREM2 antibody of the present disclosure may be administered to an individual in need of treatment with the anti-TREM2 antibody, preferably a human, in accord with known methods, such as intravenous administration as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intracerobrospinal, intracranial, intraspinal, subcutaneous, intra-articular, intrasynovial, intrathecal, oral, topical, or inhalation routes.
10676525/11634489: as regards dosing at least 15 mg/kg is envisaged
[0377] For in vivo administration of any of the anti-TREM2 antibodies of the present disclosure, normal dosage amounts may vary from about 10 ng/kg up to about 100 mg/kg of an individual's body weight or more per day, preferably about 1 mg/kg/day to 10 mg/kg/day, depending upon the route of administration. For repeated administrations over several days or longer, depending on the severity of the disease, disorder, or condition to be treated, the treatment is sustained until a desired suppression of symptoms is achieved.
[0378] An exemplary dosing regimen may include administering an initial dose of an anti-TREM2 antibody, of about 2 mg/kg, followed by a weekly maintenance dose of about 1 mg/kg every other week. Other dosage regimens may be useful, depending on the pattern of pharmacokinetic decay that the physician wishes to achieve. For example, dosing an individual from one to twenty-one times a week is contemplated herein. In certain embodiments, dosing ranging from about 3 μg/kg to about 2 mg/kg (such as about 3 μg/kg, about 10 μg/kg, about 30 μg/kg, about 100 μg/kg, about 300 μg/kg, about 1 mg/kg, and about 2/mg/kg) may be used. In certain embodiments, dosing frequency is three times per day, twice per day, once per day, once every other day, once weekly, once every two weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, or once monthly, once every two months, once every three months, or longer. Progress of the therapy is easily monitored by conventional techniques and assays. The dosing regimen, including the anti-TREM2 antibody administered, can vary over time independently of the dose used.
Under MPEP 2144.05 In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960) (MPEP 716.02(d)).
10676525/11634489: as regards treatment of disease or injury
[0027] Other aspects of the present disclosure relate to a method of preventing, reducing risk, or treating an individual having a disease, disorder, or injury selected from the group consisting of dementia, frontotemporal dementia, Alzheimer's disease, Nasu-Hakola disease, cognitive deficit, memory loss, spinal cord injury, traumatic brain injury, multiple sclerosis, chronic colitis, ulcerative colitis, and cancer, comprising administering to an individual in need thereof a therapeutically effective amount of the antibody of the preceding embodiments. In some embodiments, the disease, disorder, or injury is Alzheimer's disease.
Multiple Sclerosis
[0181] Multiple sclerosis (MS) can also be referred to as disseminated sclerosis or encephalomyelitis disseminata. MS is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are contained within an insulating substance called myelin. In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals. MS onset usually occurs in young adults, and is more common in women.
(105) Anti-TREM2 antibodies of the present disclosure can be used to prevent, reduce risk of, or treat dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, amyotrophic lateral sclerosis, Huntington's disease, tauopathy disease, Nasu-Hakola disease, stroke, acute trauma, chronic trauma, cognitive deficit, memory loss, lupus, acute and chronic colitis, rheumatoid arthritis, wound healing, Crohn's disease, inflammatory bowel disease, ulcerative colitis, obesity, malaria, essential tremor, central nervous system lupus, Behcet's disease, Parkinson's disease,
(402) Nasu-Hakola Disease
(403) Nasu-Hakola disease (NHD), which may alternatively be referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
Applicants have not provided sufficient explanation how the claim amendments overcome the obviousness rejection based on the disclosures in the reference art and the effective caselaw under K.S.R. The rejection is maintained.
10. The rejection of Claims 1 and 3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, 69-70 and 86 under 35 U.S.C. 103 as being obvious over Schwabe et al (USPN 10676525 or USPN 11634489) are moot for the canceled claims and maintained for the pending claims.
The pending claims are 2-3, 5-6, 17, 22-23, 26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, 69-70 and 86.
Pending claims 3, 5-6, 17, 22-23, 26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, 69and 86 depend from Claim 2.
Claim 70 is an independent claim.
New claim 86 depends from Claim 2 and recites the anti-TREM2 antibody is administered about once every four weeks at a dose of about 60 mg/kg (see [0011] for support).
Applicants allege Claims 3, 5, 6, 17, 22, 23, 25, 26, 32, 34, 36, 37, 39, 40, 44, 46, 48, 51, 52, 54, 55, 57-59, 65, 69, 70, and new claim 86 depend directly or indirectly from claim 2. As discussed above, claim 2 and dependent claims therefrom are not obvious over Schwabe.
Response to Arguments
The grounds for rejection of claim 2 over Schwabe is maintained for reasons of record. The cancellation of claim 1 is acknowledged. The incomplete response to the outstanding grounds for rejection of the current pending dependent claims is also acknowledged. The response is incomplete.
“Claims 17, 19 and 23 are drawn to the anti-TTEM2 antibody where element (i) comprises the VHCDR1-3/ VLCDR1-3 of the AL2p-58 clone and element (ii) comprises the VHCDR1-3/ VLCDR1-3 of the AL2p-47 clone.
Each of the patent references teach and claim the corresponding anti-TREM2 antibody for AL2p-58 and Al2p-47 at [0019; 0025; 0036; 0096; 0153; 0154].
[0164] In some embodiments, anti-TREM2 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable region comprises an HVR-H1 comprising the amino acid sequence YAFSSQWMN (SEQ ID NO: 132), an HVR-H2 comprising the amino acid sequence RIYPGGGDTNYAGKFQG (SEQ ID NO: 135), an HVR-H3 comprising the amino acid sequence ARLLRNQPGESYAMDY (SEQ ID NO: 126), and the light chain variable region comprises an HVR-L1 comprising the amino acid sequence RSSQSLVHSNGYTYLH (SEQ ID NO: 130), an HVR-L2 comprising the amino acid sequence KVSNRFS (SEQ ID NO: 131), and an HVR-L3 comprising the amino acid sequence SQSTRVPYT (SEQ ID NO: 129) of which sequences correspond to the AL2p-58 clone.
[0164] In some embodiments, anti-TREM2 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable region comprises an HVR-H1 comprising the amino acid sequence YAFSSDWMN (SEQ ID NO: 136), an HVR-H2 comprising the amino acid sequence RIYPGEGDTNYARKFHG (SEQ ID NO: 137), an HVR-H3 comprising the amino acid sequence ARLLRNKPGESYAMDY (SEQ ID NO: 138), and the light chain variable region comprises an HVR-L1 comprising the amino acid sequence RTSQSLVHSNAYTYLH (SEQ ID NO: 139), an HVR-L2 comprising the amino acid sequence KVSNRVS (SEQ ID NO: 140), and an HVR-L3 comprising the amino acid sequence SQSTRVPYT (SEQ ID NO: 129).
Each of the patent references teaches treating diseases such as
[0027] Other aspects of the present disclosure relate to a method of preventing, reducing risk, or treating an individual having a disease, disorder, or injury selected from the group consisting of dementia, frontotemporal dementia, Alzheimer's disease, Nasu-Hakola disease, cognitive deficit, memory loss, spinal cord injury, traumatic brain injury, multiple sclerosis, chronic colitis, ulcerative colitis, and cancer, comprising administering to an individual in need thereof a therapeutically effective amount of the antibody of the preceding embodiments. In some embodiments, the disease, disorder, or injury is Alzheimer's disease.
Each of the patent references teaches delaying progression of diseases or injuries
[0043] For prophylactic use, beneficial or desired results include results such as eliminating or reducing the risk, lessening the severity, or delaying the onset of the disease, including biochemical, histological and/or behavioral symptoms of the disease, its complications and intermediate pathological phenotypes presenting during development of the disease. An effective amount of drug, compound, or pharmaceutical composition is an amount sufficient to accomplish prophylactic or therapeutic treatment either directly or indirectly. As is understood in the clinical context, an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in conjunction with another drug, compound, or pharmaceutical composition. Thus, an “effective amount” may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable result may be or is achieved.
Each of the patent references teaches treating diseases using intravenous dosage regimens for the antibody clones
[0375] Pharmaceutical compositions of the present disclosure containing an anti-TREM2 antibody of the present disclosure may be administered to an individual in need of treatment with the anti-TREM2 antibody, preferably a human, in accord with known methods, such as intravenous administration as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intracerobrospinal, intracranial, intraspinal, subcutaneous, intra-articular, intrasynovial, intrathecal, oral, topical, or inhalation routes.
Claims 1, 3 5-6 and 69 are drawn to dose regimens. New claim 86 depends from Claim 2 and recites the anti-TREM2 antibody is administered about once every four weeks at a dose of about 60 mg/kg.
Each of the patent references teaches treating / delaying progression of diseases or injuries using dosage regimens for the antibody clones
[0377] For in vivo administration of any of the anti-TREM2 antibodies of the present disclosure, normal dosage amounts may vary from about 10 ng/kg up to about 100 mg/kg of an individual's body weight or more per day, preferably about 1 mg/kg/day to 10 mg/kg/day, depending upon the route of administration. For repeated administrations over several days or longer, depending on the severity of the disease, disorder, or condition to be treated, the treatment is sustained until a desired suppression of symptoms is achieved.
[0378] An exemplary dosing regimen may include administering an initial dose of an anti-TREM2 antibody, of about 2 mg/kg, followed by a weekly maintenance dose of about 1 mg/kg every other week. Other dosage regimens may be useful, depending on the pattern of pharmacokinetic decay that the physician wishes to achieve. For example, dosing an individual from one to twenty-one times a week is contemplated herein. In certain embodiments, dosing ranging from about 3 μg/kg to about 2 mg/kg (such as about 3 μg/kg, about 10 μg/kg, about 30 μg/kg, about 100 μg/kg, about 300 μg/kg, about 1 mg/kg, and about 2/mg/kg) may be used. In certain embodiments, dosing frequency is three times per day, twice per day, once per day, once every other day, once weekly, once every two weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, or once monthly, once every two months, once every three months, or longer. Progress of the therapy is easily monitored by conventional techniques and assays. The dosing regimen, including the anti-TREM2 antibody administered, can vary over time independently of the dose used.
Under MPEP 2144.05 In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960) (MPEP 716.02(d)).
Claim 22 is drawn to the features of the antibody isotype.
Each of the patent references teaches the antibody comprising the Fc with substitutions for P331S and E430G.
[0023] In some embodiments that may be combined with any of the preceding embodiments, the antibody is of the IgG class, the IgM class, or the IgA class. In some embodiments that may be combined with any of the preceding embodiments, the antibody is of the IgG class and has an IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments that may be combined with any of the preceding embodiments, the antibody comprises one or more amino acid substitutions in the Fc region at a residue position selected from the group consisting of: C127S, L234A, L234F, L235A, L235E, S267E, K322A, L328F, A330S, P331S, E345R, E430G, S440Y, and any combination thereof,
Claim 25 is drawn to the disease.
Each of the patent references teaches the disease comprising
[0027] Other aspects of the present disclosure relate to a method of preventing, reducing risk, or treating an individual having a disease, disorder, or injury selected from the group consisting of dementia, frontotemporal dementia, Alzheimer's disease, Nasu-Hakola disease, cognitive deficit, memory loss, spinal cord injury, traumatic brain injury, multiple sclerosis, chronic colitis, ulcerative colitis, and cancer, comprising administering to an individual in need thereof a therapeutically effective amount of the antibody of the preceding embodiments. In some embodiments, the disease, disorder, or injury is Alzheimer's disease.
Claims 34 and 51 are drawn to a TREM2 mutation.
Each of the patent references teaches a TREM2 mutation
[0539] TREM2 is produced as a cell surface receptor that can be cleaved to release the extracellular domain. A rare TREM2 mutation in humans (H157Y) causes increased production of sTREM2 and increases the risk of development of late onset Alzheimer's disease (Thornton et al, EMBO Mol Med 2017, 9(10): 1366-78).
Claims 36, 46, 48, 52, 54 and 55 are drawn to biomarkers and measurement thereof.
Each of the patent references teaches measurement of disease-related biomarkers such a tau or amyloid
[0129] Useful assays may include western blots (e.g., for tyrosine-phosphotylated DAP12 or threonine/serine-phosphorylated PI3K-kinase substrates), ELISA (e.g., for secreted interleukin or cytokine secretion), FACS (e.g., for anti-TREM2 binding to TREM2), immunocytochemistry (e.g., for e.g., for tyrosine-phosphorylated DAP12 or threonine/serine-phosphorylated PI3K-kinase substrates), reporter-gene assays (e.g., for TLR activation), increased survival and/or function of dendritic cells, macrophages, monocytes, osteoclasts, Langerhans cells of skin, Kupffer cells, and/or microglia, increased phagocytosis of apoptotic neurons, damaged synapses, amyloid beta or fragments thereof, Tau, IAPP, alpha-synuclein, TDP-43, FUS protein, prion protein, PrPSc, huntingtin, calcitonin, superoxide dismutase, ataxin, Lewy body, atrial natriuretic factor, islet amyloid polypeptide, insulin, apolipoprotein Al, serum amyloid A, medin, prolactin, transthyretin, lysozyme, beta 2 microglobulin, gelsolin, keratoepithelin, cystatin, immunoglobulin light chain AL, S-IBM protein, Repeat-associated non-ATG (RAN) translation products, Dipeptide repeat (DPR) peptides, glycine-alanine (GA) repeat peptides, glycine-proline (GP) repeat peptides, glycine-arginine (GR) repeat peptides, proline-alanine (PA) repeat peptides, and proline-arginine (PR) repeat peptides, nerve tissue debris, non-nerve tissue debris, bacteria, other foreign bodies, disease-causing proteins, disease-causing peptides, disease-causing nucleic acid, or tumor cells by macrophages, dendritic cells, Langerhans cells of skin, Kupffer cells, monocytes, osteoclasts, and/or microglial cells, increased cytoskeleton reorganization, and decreased microglial pro-inflammatory responses, or other assays known in the art.
Claims 37, 39-40, 44 and 70 are drawn to measurement soluble TREM2.
Each of the patent references teaches measurement of soluble TREM2
[0009] In some embodiments, anti-TREM2 antibodies of the present disclosure may also decreases plasma levels of soluble TREM2 in vivo. In some embodiments, anti-TREM2 antibodies of the present disclosure may also decrease soluble TREM2. In some embodiments, the soluble TREM2 is decreased about any of 10, 20, 30, 40, 50 or 60%.
[0025] In some embodiments that may be combined with any of the preceding embodiments, the antibody decreases plasma levels of soluble TREM2 in vivo by an amount that is at least 25% greater than that of a human control IgG1 antibody. In some embodiments that may be combined with any of the preceding embodiments, the antibody decreases plasma levels of soluble TREM2 in vivo by blocking cleavage, by inhibiting one or more metalloproteases, and/or by inducing internalization. In some embodiments, soluble TREM2 is decreased by about any of 10, 20, 30, 40, or 50%.
Claims 26, 32 57-59 and 65 are drawn to PET imaging of the individual.
Each of the patent references teaches measurement of soluble TREM2
[0463] In some embodiments, the individual is a human. In some embodiments, the individual is a human patient suffering from, or at risk for developing, cancer. In some embodiments, the diagnostic methods involve detecting TREM2 in a biological sample, such as a biopsy specimen, a tissue, or a cell. An isolated antibody of the present disclosure (e.g., an anti-TREM2 antibody described herein) is contacted with the biological sample and antigen-bound antibody is detected. For example, a tumor sample (e.g., a biopsy specimen) may be stained with an anti-TREM2 antibody described herein in order to detect and/or quantify tumor-associated macrophages (e.g., M2-type macrophages). The detection method may involve quantification of the antigen-bound antibody. Antibody detection in biological samples may occur with any method known in the art, including immunofluorescence microscopy, immunocytochemistry, immunohistochemistry, ELISA, FACS analysis, immunoprecipitation, or micro-positron emission tomography. In certain embodiments, the antibody is radiolabeled, for example with .sup.18F and subsequently detected utilizing micro-positron emission tomography analysis. Antibody-binding may also be quantified in a patient by non-invasive techniques such as positron emission tomography (PET), X-ray computed tomography, single-photon emission computed tomography (SPECT), computed tomography (CT), and computed axial tomography (CAT).”
The response is incomplete and the rejection is maintained.
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.
11. A. The rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 and 86 on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11634489 is moot for the canceled claims and maintained for the pending claims. The patent reference is not afforded safe harbor under 35 USC 121 because it shares no continuity with nor a restriction/speciation with the claims of the instant application. The instant application is outside of the family of cases to which U.S. Patent No. 11634489 corresponds.
B. The rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 and 86 on the ground of nonstatutory double patenting as being unpatentable over claims 1-60 of U.S. Patent No. 10676525 is moot for the canceled claims and maintained for the pending claims. The patent reference is not afforded safe harbor under 35 USC 121 because it shares no continuity with nor a restriction/speciation with the claims of the instant application. The instant application is outside of the family of cases to which U.S. Patent No. 10676525 corresponds.
C. The provisional rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 and 86 on the ground of nonstatutory double patenting as being unpatentable over claims 7, 11, 16-19, 23-28, 31-37, 40-47, 55-65 of copending Application No. 18/174,499 (reference application US 20230312712) is moot for the canceled claims and maintained for the pending claims.
Applicants request to hold the rejection in abeyance is granted.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. The provisional rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 and 86 on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 5-9, 11, 13, 23, 25, 27, 29-34, 39, 41, 44, 46-47, 51, 54, 67-68, 73, 77-79 of copending Application No. 18/806,118 (reference application US 20250084165) is moot for the canceled claims and maintained for the pending claims. Applicants request to hold the rejection in abeyance is granted.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
13. The provisional rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 and 86 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8-11, 13, 15, 17, 19-22, 25-29, 31, 33, 35-39 of copending Application No. 17/801,776 (reference application US 20230159637) is moot for the canceled claims and maintained for the pending claims. Applicants request to hold the rejection in abeyance is granted.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
14. The provisional rejection of Claims 1-3, 5-6, 17, 19, 22-23, 25-26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, and 69-70 and 86 on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 15-17, 19, 21, 23, 25-32, 35, 39, 41-42 of copending Application No. 17/782127 (reference application US 20230024528) is moot for the canceled claims and maintained for the pending claims. Applicants request to hold the rejection in abeyance is granted.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
New Grounds for Rejection
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.
15. Claims 2-3, 5-6, 17, 22-23, 26, 32, 34, 36-37, 39-40, 44, 46, 48, 51-52, 54-55, 57-59, 65, 69 and 86 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.
A) A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation a demyelination disorder, and the claim also recites multiple sclerosis which is the narrower statement of the range/limitation.
The specification provides example of a demyelination with MS
Multiple Sclerosis
[0181] Multiple sclerosis (MS) can also be referred to as disseminated sclerosis or encephalomyelitis disseminata. MS is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are contained within an insulating substance called myelin. In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals. MS onset usually occurs in young adults, and is more common in women.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
16. Claim 17 is 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.
Claim 17(i) recites identical VH/VL CDR1-3 for the ALP2p-58 clone of amended Claim 2, and from which claim 17 depends. Element (i) of claim 17 is not further limiting as a dependent claim.
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
17. No claims are allowed.
18. 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.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643