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 Application/Election/Restrictions
Applicant’s election without traverse of phosphatidylserine for the species of TREM2 ligands; DAP12 phosphorylation for the species of TREM2 activities; TNF-a for the species of pro-inflammatory mediators; microglial cells for the species of cells; CD83 for the species of stimulatory molecules; amino acid residues 149-157 of SEQ ID NO:1 or amino acid residues on a TREM2 protein corresponding to aa 149-157 of SEQ ID NO:1 for the species of epitope; SEQ ID NOs:34-35, 31 and 41, 33 and 32 for HVR-H1-H3 and HVR-L1-L3; SEQ ID NOs: 27 and 30 for HVR and LVR; SEQ ID NOs: 44 and 47 for HC and LC; ALSP (adult-onset leukoencephalopathy with axonal spheroids and pigmented glia) for species of CSF1R-deficient disease; leukoencephalopathy for species of disease characteristics; abnormality of the cerebral white matter for the species of symptoms in the reply filed on July 28, 2025 is acknowledged.
Claims 12-14, 18, 20, 22, 24, 33-34, 36-38, 40 and 43-44 are canceled. Claims 1-11, 15-17, 19, 21, 23, 25-32, 35, 39 and 41-42 are pending in this application. Claims 23, 30 and 41 are withdrawn without traverse (filed 12/08/2025) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Upon reconsideration, the species election for different species of TREM2 activities recited in claim 10 and for different ligands recited in claim 5 is withdrawn. The subject matter to the extent of different species of TREM2 activities and different TREM2 ligands is included and under examination in this office action. Election was made without traverse in the reply filed on July 28, 2025.
Claims 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 are under examination with respect to amino acid residues 149-157 of SEQ ID NO:1 or amino acid residues on a TREM2 protein corresponding to aa 149-157 of SEQ ID NO:1 for epitope; SEQ ID NOs:34-35, 31 and 41, 33 and 32 for HVR-H1-H3 and HVR-L1-L3; SEQ ID NOs: 27 and 30 for HVR and LVR; SEQ ID NOs: 44 and 47 for HC and LC and ALSP for disease in this office action.
Specification
The disclosure is objected to because of the following informalities: The recitations “HVR-H1, HVR-H and HVR-H3” and “HVR-L1, HVR-L2 and HVR-3” recited in paragraphs [0019], [0021]; [0043]-[0064]; [0176]-[0178]; [0180]; [0183]-[0188] and across the whole specification and table are inconsistent with the recitations of “CDR-H1, CDR-H2, CDR-H3” and “CDR-L1, CDR-L2, CDR-L3” and “VH and VL” recited in p. 56-66, table B because it is not known whether the recitations “HVR-H1, HVR-H and HVR-H3” and “HVR-L1, HVR-L2 and HVR-3” are the same as “CDR-H1, CDR-H2 and CDR-H3” encompassed within a heavy chain variable region (VH) and “CDR-L1, CDR-L2 and CDR-L3” encompassed within a light chain variable region (VL). It is unclear what Applicant intended to include within the scope of the claims. If the limitation “HVR-H1, HVR-H and HVR-H3” means three Complementarity Determining Regions (CDR-H1-CDR-H3) encompassed within a heavy chain variable region (VH) and the limitation “HVR-L1, HVR-L2 and HVR-3” means three Complementarity Determining Regions (CDR-L1-CDR-L3) encompassed within a light chain variable region (VL), Applicant is required to spell out the limitations and use common abbreviations known in the art. Appropriate correction is required.
Claim Objections
Claims 1-11, 15-16, 19, 21, 31, 35, and 42 are objected to because of the following informalities: The recitations “CSF1R”, “TREM2”, “APOE”, “DAP12”, “Syk”, “MCP-1/CCL2, CCL3, CCL4, CCL5, CCR2, CXCL-10”, “OSM, CNTF, CSF-1, OPN” and the recitations “HVR-H1, HVR-H and HVR-H3” and “HVR-L1, HVR-L2 and HVR-3” in claims 1-11, 15-16, 19, 21, 31, 35, and 42 are not unique or common abbreviations in the art. Applicants are required to spell out “CSF1R”, “TREM2”, “APOE”, “DAP12”, “Syk”, “MCP-1/CCL2, CCL3, CCL4, CCL5, CCR2, CXCL-10”, “OSM, CNTF, CSF-1, OPN” and “HVR-H1, HVR-H and HVR-H3” and “HVR-L1, HVR-L2 and HVR-3” at the first usage. 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 21 and 42 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 21 and 42 are indefinite because:
i. Claim 21 recites the limitation "an HVR-H1, HVR-H and HVR-H3” and “an HVR-L1, HVR-L2 and HVR-3” in the claim. It is unclear whether the limitation "an HVR-H1, HVR-H and HVR-H3” means three Complementarity Determining Regions (HCDRs1-3) encompassed within a heavy chain variable region (VH) or other structures, and the limitation “HVR-L1, HVR-L2 and HVR-3” means three Complementarity Determining Regions (LCDRs1-3) encompassed within a light chain variable region (VL) or other structures. It is unclear what Applicant intended to include within the scope of the claims. Since the metes and bounds of what is encompassed within the limitations "an HVR-H1, HVR-H and HVR-H3” and “an HVR-L1, HVR-L2 and HVR-3”, a skilled artisan cannot envision what is included in the claims. Thus, the claim is indefinite. For examination purposes, the limitations "an HVR-H1, HVR-H and HVR-H3 and “an HVR-L1, HVR-L2 and HVR-3” are interpretated as “HCDRs1-3” and “LCDRs1-3” respectively.
ii. Claim 42 recites the limitation "the treatment" in line 1 of the claim and “the level…” in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
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 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 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. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue’. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)”. See MPEP § 2164.01.
Claims 1-11, 15-17, 19, 21, 25-29, 31-32, 35 and 39 are drawn to a method for treating or preventing a CSF1R-deficient disease including adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) or pediatric-onset leukoencephalopathy, comprising administering to an individual in need thereof a therapeutically effective amount of an anti-TREM2 agonist antibody including anti-TREM2 agonist antibody binding 149-157 of SEQ ID NO:1, one or more amino acid residues recited in claim 19, an anti-TREM2 agonist antibody having recited SEQ ID NOs; 34-35, 31 and 41, 33 and 32 for HCDRs1-3 and LCDRs1-3 respectively or having SEQ ID NOs: 27 and 30 for VH and VL respectively or having SEQ ID NOs: 44 and 47 for HC and LC respectively.
Claim 42 is drawn to a method of monitoring the treatment of an individual being administering an anti-TREM2 antibody, comprising measuring the level of CSF1R in a sample from the individual before and after the individual has received one or more doses of an anti-TREM2 antibody, which includes structurally and functionally undefined anti-TREM2 antibody including structurally and functionally undefined anti-TREM2 agonist antibody or anti-TREM2 antagonist antibody.
The instant invention is based on findings that:
i) treatment of cultured human macrophages with an anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG (comprising SEQ ID NOs: 43/44 and 47 for heavy chain and light chain listed in Table B) in a culture medium supplemented with an anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG increased cell viability of human macrophages in cultures compared to M-CSF alone (Example 1);
ii) treatment of cultured human macrophages with an anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG in culture medium comprising AL2p-58 huIgG1 PSEG in the presence of a CSF1R inhibitor PLX3397 in vitro reduced cell death induced by the CSF1R inhibitor PLX3397 in human macrophage cultures compared to an IgG1 control in the presence of CSF1R inhibitor PLX3397 (Example 2); and
iii) detecting an increased expression level of CSF1R protein in samples isolated from the frontal cortex of the normal non-human primates after administration of an anti-TREM2 antibody: AL2p-58 huIgG1 PSEG antibody to normal non-human primates by intravenous injection for a total of five doses compared to the samples isolated from the non-human primates treated with a control IgG (Example 3) or detecting an increased expression level of CSF1R protein in samples isolated the frontal cortex and the hippocampus of the normal non-human primates after administration of an anti-TREM2 antibody: AL2p-58 HuIgG1 antibody to the normal non-human primates by intravenous injection for a total of five doses compared to the samples isolated from the non-human primates treated with a control IgG.
Applicant extrapolates the above findings to the claimed method of treating or preventing all forms of CSF1R-deficient disease including ALSP or pediatric-onset leukoencephalopathy comprising administering to an individual in need thereof a therapeutically amount of an anti-TREM2 agonist antibody and the claimed method of monitoring the treatment of an individual being administered an anti-TREM2 antibody subject by measuring the level of CSF1R in a sample from the individual before and after the individual has received one or more doses of an anti-TREM2 antibody.
First, Applicant is not enabled for a method for treating or preventing a CSF1R-deficient disease including all forms of diseases resulting from deficiencies or other defects in CSF1R signaling or a CSF1R protein with reduced function compared to wild type CSF1R protein or caused by a mutation in the CSF1R gene including a missense mutation, an indel, or a mutation generating a truncated protein product including ALSP or pediatric-onset leukoencephalopathy by the claimed anti-TREM2 agonist antibody in view of paragraphs [0092]-[0110] of the published application.
The instant claims recite the limitation “a CSF1R-deficient disease”, which includes all forms of diseases resulting from deficiencies or other defects in CSF1R signaling or a CSF1R protein with reduced function compared to wild type CSF1R protein or caused by a mutation in the CSF1R gene including a missense mutation, an indel, or a mutation generating a truncated protein product in view of paragraph [0092] of the specification and “wherein the CSF1R-defiicent disease is ALSP or pediatric-onset leukoencephalopathy". However, neither the specification nor the prior art provides guidance as to how to prevent a person from having a CSF1R-deficient disease including ALSP or pediatric-onset leukoencephalopathy. The claimed CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy are genetic inherited diseases and are caused by genetic mutations in CSF1R gene, which is a nature process and cannot be prevented. ALSP is an autosomal dominant genetic disease caused by dominantly inherited, monoallelic or heterozygous mutations in CSF1R gene. Pediatric-onset leukoencephalopathy is an autosomal recessive inherited diseases and caused by homozygous mutations in CSF1R gene. Currently, there is no treatment to prevent development of CSF1R-deficient diseases as evidenced by Chitu et al. (The FEBS J, 2022; 289:5049-5073).
Any individual has a potential to develop any form of CSF1R-deficient disease including ALSP or pediatric-onset leukoencephalopathy. Applicant fails to teach how to identify or predict when and which person among us would be susceptible to such a disease or developing the disease, and predict when the person would need administration of the claimed anti-TREM2 agonist antibody to prevent the disease including ALSP or pediatric-onset leukoencephalopathy. Neither the specification nor the prior art teaches that administration of the claimed anti-TREM2 agonist antibody can prevent a person from getting any forms of CSF1R-deficient disease including ALSP or pediatric-onset leukoencephalopathy. The cause of the disease is due to a genetic deficit or mutations in CSF1R gene, which is a natural process. It is impossible to prevent a person from getting or developing all forms of CSF1R-deficient disease including ALSP or pediatric-onset leukoencephalopathy before the disease occurs or diagnosed because the genetic deficit or mutations in CSF1R gene is a natural process result. The specification fails to provide sufficient guidance as to enable one of skill in the art to practice the invention as it pertains to a method of preventing a CSF1R-deficient disease including ALSP or pediatric-onset leukoencephalopathy by any given agent. Further, Applicant also fails to provide specific guidance as to what specific amount of the claimed anti-TREM2 agonist antibody can be used and thus would be effective to prevent all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy caused by the genetic deficit or mutations in CSF1R gene. Thus, a skilled artisan cannot contemplate a right amount to prevent the disease or to prevent a person from getting the disease.
Second, the specification provides insufficient guidance to enable a skilled artisan to treat all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy caused by the genetic deficit or mutations in CSF1R gene.
Based on the specification and the prior art, Applicant is enabled for detecting an increased expression level of CSF1R protein in samples isolated from the frontal cortex of the normal non-human primates after administration of an anti-TREM2 antibody: AL2p-58 huIgG1 PSEG antibody or AL2p-58 HuIgG1 antibody to normal non-human primates by intravenous injection for a total of five doses compared to the samples isolated from the non-human primates treated with a control IgG (Example 3) or detecting an increased expression level of CSF1R protein in samples isolated the frontal cortex and the hippocampus of the normal non-human primates after administration of an anti-TREM2 antibody: AL2p-58 HuIgG1 antibody to the normal non-human primates by intravenous injection for a total of five doses compared to the samples isolated from the non-human primates treated with a control IgG (Example 4). Applicant is also enabled for increasing cell viability of cultured human macrophages in a culture medium supplemented with an anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG compared to M-CSF alone in vitro or reducing cell death induced by the CSF1R inhibitor PLX3397 in cultured human macrophages in culture medium comprising AL2p-58 huIgG1 PSEG in the presence of a CSF1R inhibitor PLX3397 in vitro compared to an IgG1 control in the presence of CSF1R inhibitor PLX3397 (Examples 1-2).
However, the claims are not limited to the agents and methods set forth above. The claims encompass treatment of all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy caused by the genetic deficit or mutations in CSF1R gene and using a structurally and functionally undefined anti-TREM2 agonist antibody or a structurally and functionally undefined anti-TREM2 agonist antibody binding 149-157 of SEQ ID NO:1, one or more amino acid residues recited in claim 19, an anti-TREM2 agonist antibody having recited SEQ ID NOs; 34-35, 31 and 41, 33 and 32 for HCDRs1-3 and LCDRs1-3 respectively or having SEQ ID NOs: 27 and 30 for VH and VL respectively or having SEQ ID NOs: 44 and 47 for HC and LC respectively.
While the skill level in the art is high, the level of predictability is low. The specification fails to provide sufficient guidance to enable one of skill in the art to practice the claimed invention without undue experimentation because of the complexity and unpredictability of the diseases and failure to provide support for a well-established correlation between the normal non-human primates without any disease or gene deficits and all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo.
The effects of the anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG or AL2p-58 HuIgG1 on the increased expression level of CSF1R protein in samples isolated the frontal cortex and/or the hippocampus of the normal non-human primates shown in Examples 3-4 of the instant specification are under the condition that the normal non-human primates still possess a functional CSF1R gene that can still express the CSF1R protein or functional CSF1R protein to have functional CSF1R signaling that is associated with the agonist effect by the anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG or AL2p-58 HuIgG1.
However, CSF1R-deficient diseases include any disease, disorder or condition resulting from deficiencies or other defects in CSF1R signaling or a CSF1R protein with reduced function compared to wild type CSF1R protein or caused by a mutation in the CSF1R gene including a missense mutation, an indel, or a mutation generating a truncated protein product in view of paragraphs [0092]-[0110] of the published application. The patients with CSF1R-deficient diseases including diseases resulting from deficiencies or other defects in CSF1R signaling, a missense mutation, an indel or a mutation in CSF1R gene generating a truncated protein product, or diseases including ALSP or pediatric-onset leukoencephalopathy caused by genetic deficits or mutations in CSF1R gene have CSF1R deficiency, and do not have a functional CSF1R protein or have no functional CSF1R signaling, which result in development of skeletal dysplasia, brain disorder and developmental anomalies including ventriculomegaly and cerebellar atrophy, as well as leukodystrophy (see Dulski et al. CSF1R-Related Disorder. 2012 Aug 30 [Updated 2024 Apr 4]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026) and Chitu et al. (The FEBS J, 2022; 289:5049-5073).
[0092] “CSF1R-deficient disease,” as used herein, refers to any disease, disorder or condition resulting from deficiencies or other defects in CSF1R signaling. In certain embodiments, the disease, disorder or condition involves a CSF1R protein with reduced function as compared to CSF1R protein considered to have “wild type” function or that has function considered to be within normal range. In some embodiments, CSF1R-deficient diseases are characterized by a mutation in the CSF1R gene in the affected individual. The mutation typically results in reduced function of CSF1R in the affected individual. The mutation may be of any type, including, for example, a missense mutation, an indel, or a mutation generating a truncated protein product.
The specification fails to teach that all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases resulting from deficiencies or other defects in CSF1R signaling in vivo can still express functional CSF1R protein for the CSF1R signaling. The specification also fails to teach that functional CSF1R signaling or the expression of CSF1R protein and/or functional CSF1R protein for the CSF1R signaling can be induced by administration of the claimed the anti-TREM2 agonist antibody recited in instant claims or any anti-TREM2 antibody including anti-TREM2 agonist and antagonist antibodies as recited in claim 42, and thereby treating or preventing the CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene. Thus, it is unpredictable whether administration of the claimed TREM2 agonist antibody with no defined structure or the TREM2 agonist antibody AL2p-58 huIgG1 PSEG or AL2p-58 HuIgG1 can treat all forms of the claimed CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo, indicating that undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Further, the specification fails to provide sufficient guidance as to what other anti-TREM2 agonist antibodies are and whether all anti-TREM2 agonist antibodies including anti-TREM2 agonist antibody binding 149-157 of SEQ ID NO:1 or TREM2 variants, binding one or more amino acid residues recited in claim 19 an anti-TREM2 agonist antibody having recited SEQ ID NOs; 34-35, 31 and 41, 33 and 32 for HCDRs1-3 and LCDRs1-3 respectively or having SEQ ID NOs: 27 and 30 for VH and VL respectively or having SEQ ID NOs: 44 and 47 for HC and LC respectively can be used in the claimed method because a single amino acid change on a molecule can abolish the binding ability of the molecule. For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210).
The specification also provides no structural and functional relationship between the claimed anti-TREMs agonist antibody and the anti-TREM2 antibody AL2p-58 huIgG1 PSEG (comprising SEQ ID NOs: 43/44 and 47 for heavy chain and light chain as listed in Table B) or AL2p-58 HuIgG1 in increasing an expression level of CSF1R protein in samples isolated the frontal cortex and/or the hippocampus of the normal non-human primates after administration of the AL2p-58 huIgG1 PSEG or AL2p-58 HuIgG1 antibody to the normal non-human primates by intravenous injection for a total of five doses compared to the samples isolated from the non-human primates treated with a control IgG or even in treatment of all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo. The specification fails to teach what other structures/amino acid sequences can or cannot not be included/changed in all anti-TREM2 agonist antibodies in order to preserve the activity of anti-TREM2 antibody AL2p-58 huIgG1 PSEG (comprising SEQ ID NOs: 43/44 and 47 for heavy chain and light chain as listed in Table B) or AL2p-58 HuIgG1 in increasing an expression level of CSF1R protein in samples isolated the frontal cortex and/or the hippocampus of the normal non-human primates or even in treating or preventing all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo, indicating that undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, the limited examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform in order to practice the claimed invention as it pertains to a method for treating or preventing a CSF1R-deficient diseases by the claimed anti-TREM2 agonist antibody or monitoring the treatment of an individual being administered with the claimed anti-TREM2 agonist antibody.
Claim Rejections - 35 USC § 112
Claims 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 encompass using a genus of anti-TREM2 agonist antibodies for treating or preventing a genus of CSF1R-deficient diseases. Claim 17 encompasses using a genus of bispecific anti-TREM2 agonist antibodies, multivalent anti-TREM2 agonist antibodies. Claim 19 encompasses using a genus of anti-TREM2 agonist antibodies binding to TREM2 variants, or a genus of anti-TREM2 agonist antibodies binding to aa 149-157 of SEQ ID NO:1, one or more amino acid residues recited in claim 19. Claim 21 encompasses using an anti-TREM2 agonist antibody having recited SEQ ID NOs; 34-35, 31 and 41, 33 and 32 for HCDRs1-3 and LCDRs1-3 respectively or having SEQ ID NOs: 27 and 30 for VH and VL respectively or having SEQ ID NOs: 44 and 47 for HC and LC respectively. Claim 42 encompasses using a genus of anti-TREM2 antibodies including agonist and antagonist antibodies.
Applicant has not disclosed sufficient species for using the broad genus of anti-TREM2 agonist antibodies, the broad genus of bispecific anti-TREM2 agonist antibodies and multivalent anti-TREM2 agonist antibodies, the broad genus of anti-TREM2 agonist antibodies binding to aa 149-157 of SEQ ID NO:1, variants of TREM2, or one more amino acids recited in claim 20 or an anti-TREM2 agonist antibody having recited SEQ ID NOs; 34-35, 31 and 41, 33 and 32 for HCDRs1-3 and LCDRs1-3 respectively or having SEQ ID NOs: 27 and 30 for VH and VL respectively or having SEQ ID NOs: 44 and 47 for HC and LC respectively for treating the broad genus of CSF1R-deficient diseases.
The specification only disclosed that administration of the anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG antibody or AL2p-58 HuIgG1 antibody to normal non-human primates by intravenous injection for a total of five doses increased expression of CSF1R protein in samples isolated from the frontal cortex and/or hippocampus of the normal non-human primates as compared to the samples isolated from the non-human primates treated with a control IgG. However, the claims are not limited to the use of anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG antibody or AL2p-58 HuIgG1 antibody for increasing expression of CSF1R protein in samples isolated from the frontal cortex and/or hippocampus of the normal non-human primates set forth above but also encompass using structurally and functionally undefined anti-TREM2 agonist antibody for treating the broad genus of undefined CSF1R-deficient diseases.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of administration of the anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG antibody or AL2p-58 HuIgG1 antibody to normal non-human primates by intravenous injection for a total of five doses to increase expression of CSF1R protein in samples isolated from the frontal cortex and/or hippocampus of the normal non-human primates as compared to the samples isolated from the non-human primates treated with a control IgG. However, Applicant is not in possession of using the anti-TREM2 agonist antibody AL2p-58 huIgG1 PSEG antibody or AL2p-58 HuIgG1 antibody or structurally and functionally undefined anti-TREM2 agonist antibody or described in the specification for treating all forms of CSF1R-deficient diseases.
The specification provides no well-established correlation between the normal non-human primates with no disease or gene deficits and the claimed genus of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo.
The specification also provides no well-established structural and functional relationship between the claimed genus of anti-TREMs agonist antibody and the anti-TREM2 antibody AL2p-58 huIgG1 PSEG (comprising SEQ ID NOs: 43/44 and 47 for heavy chain and light chain as listed in Table B) or AL2p-58 HuIgG1 in increasing the expression level of CSF1R protein in samples isolated the frontal cortex and/or the hippocampus of the normal non-human primates after administration of the AL2p-58 huIgG1 PSEG or AL2p-58 HuIgG1 antibody to the normal non-human primates by intravenous injection for a total of five doses compared to the samples isolated from the non-human primates treated with a control IgG or even in treatment of all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo.
The specification fails to teach what other structures/amino acid sequences can or cannot not be included/changed in all anti-TREM2 agonist antibodies in order to preserve the activity of anti-TREM2 antibody AL2p-58 huIgG1 PSEG (comprising SEQ ID NOs: 43/44 and 47 for heavy chain and light chain as listed in Table B) or AL2p-58 HuIgG1 in increasing an expression level of CSF1R protein in samples isolated the frontal cortex and/or the hippocampus of the normal non-human primates or even in treating or preventing all forms of CSF1R-deficient diseases including ALSP or pediatric-onset leukoencephalopathy or caused by all forms of genetic deficit including mutations in CSF1R gene or other undefined CSF1R-deficient diseases in vivo.
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other anti-TREM2 agonist antibodies including bispecific, multivalent, binding to aa 149-157 or one or more amino acids recited in claim 19 or other anti-TREM2 antibody might be or whether administration of the anti-TREM2 agonist antibody having SEQ ID NOs; 34-35, 31 and 41, 33 and 32 for HCDRs1-3 and LCDRs1-3 respectively or having SEQ ID NOs: 27 and 30 for VH and VL respectively or having SEQ ID NOs: 44 and 47 for HC and LC respectively can treat or prevent the claimed genus of CSF1R-deficient diseases. Since the common characteristics/features of other anti-TREM2 agonist antibodies and treatment of CSF1R-deficient diseases are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of using the genus of anti-TREM2 agonist antibody for treating the genus of CSF1R-deficient diseases or using the genus of TREM2 antibody for monitoring the treatment of an TREM2 antibody based on measuring the level of CSF1R in a sample from an individual being administered the TREM2 antibody.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of anti-TREM2 agonist antibody for treating the genus of CSF1R-deficient diseases or the genus of anti-TREM2 antibody for monitoring the treatment with the anti-TREM2 antibody, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed methods have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
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 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-3, 5-6, 17, 19, 22-23, 37, 39-40, 44,46, 48, 51-52, 54, 70 and 86 of copending Application No. 17/916728. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods recited in claims of the copending Application No. 17/916728 use the same material, and the same active step in the same patient population and thus anticipate instant claims.
Claims 2-3, 5-6, 17, 19, 22-23, 37, 39-40, 44,46, 48, 51-52, 54, 70 and 86 of Application No. 17916728 (the ‘728 Application) claim a method of treating and/or delaying the progression of a disease or injury including ALSP (claim 2), which is a CSF1R-defiicent disease, in an individual, comprising administering to the individual an anti-TREM2 antibody at a dose of at least about 15 mg/kg intravenously, wherein the anti-TREM2 antibody is an agonist, wherein the anti-TREM2 agonist antibody comprises a HC of SEQ ID NO:44 and a LC of SEQ ID NO:47, which are identical to instant SEQ ID NOs: 44 and 47 respectively and a method of monitoring the treatment of an individual being administered an anti-TREM2 antibody comprising measuring the level of at least one biomarker including soluble CSF1R. Therefore, claims 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 of the instant Application are not patentably distinct from claims 2-3, 5-6, 17, 19, 22-23, 37, 39-40, 44,46, 48, 51-52, 54, 70 and 86 of the ‘728 Application because claims 1-11, 15-17, 19, 21, 25-29, 31-32, 35, 39 and 42 of the instant Application are anticipated by claims 2-3, 5-6, 17, 19, 22-23, 37, 39-40, 44,46, 48, 51-52, 54, 70 and 86 of the ‘728 Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The sequence search results disclose as follows:
SEQ ID NO:44
Sequence 44, US/17916728
Publication No. US20230183341A1
GENERAL INFORMATION
APPLICANT: ALECTOR LLC
TITLE OF INVENTION: METHODS OF USE OF ANTI-TREM2 ANTIBODIES
FILE REFERENCE: 73502-20035.00
CURRENT APPLICATION NUMBER: US/17/916,728
CURRENT FILING DATE: 2022-10-03
PRIOR APPLICATION NUMBER: PCT/US2021/025626
PRIOR FILING DATE: 2021-04-02
PRIOR APPLICATION NUMBER: US 63/079,810
PRIOR FILING DATE: 2020-09-17
PRIOR APPLICATION NUMBER: US 63/005,130
PRIOR FILING DATE: 2020-04-03
NUMBER OF SEQ ID NOS: 145
SEQ ID NO 44
LENGTH: 452
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Construct
Query Match 100.0%; Score 2407; Length 452;
Best Local Similarity 100.0%;
Matches 452; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYAFSSQWMNWVRQAPGQRLEWIGRIYPGGGDTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYAFSSQWMNWVRQAPGQRLEWIGRIYPGGGDTNY 60
Qy 61 AGKFQGRVTITADTSASTAYMELSSLRSEDTAVYYCARLLRNQPGESYAMDYWGQGTLVT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGKFQGRVTITADTSASTAYMELSSLRSEDTAVYYCARLLRNQPGESYAMDYWGQGTLVT 120
Qy 121 VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL 180
Qy 181 QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEL 240
Qy 241 LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE 300
Qy 301 QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPS 360
Qy 361 RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK 420
Qy 421 SRWQQGNVFSCSVMHGALHNHYTQKSLSLSPG 452
||||||||||||||||||||||||||||||||
Db 421 SRWQQGNVFSCSVMHGALHNHYTQKSLSLSPG 452
SEQ ID NO:47
Sequence 47, US/17916728
Publication No. US20230183341A1
GENERAL INFORMATION
APPLICANT: ALECTOR LLC
TITLE OF INVENTION: METHODS OF USE OF ANTI-TREM2 ANTIBODIES
FILE REFERENCE: 73502-20035.00
CURRENT APPLICATION NUMBER: US/17/916,728
CURRENT FILING DATE: 2022-10-03
PRIOR APPLICATION NUMBER: PCT/US2021/025626
PRIOR FILING DATE: 2021-04-02
PRIOR APPLICATION NUMBER: US 63/079,810
PRIOR FILING DATE: 2020-09-17
PRIOR APPLICATION NUMBER: US 63/005,130
PRIOR FILING DATE: 2020-04-03
NUMBER OF SEQ ID NOS: 145
SEQ ID NO 47
LENGTH: 219
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Construct
Query Match 100.0%; Score 1137; Length 219;
Best Local Similarity 100.0%;
Matches 219; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVVMTQSPDSLAVSLGERATINCRSSQSLVHSNRYTYLHWYQQKPGQSPKLLIYKVSNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVMTQSPDSLAVSLGERATINCRSSQSLVHSNRYTYLHWYQQKPGQSPKLLIYKVSNRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTRVPYTFGQGTKLEIKRTVAAPSV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTRVPYTFGQGTKLEIKRTVAAPSV 120
Qy 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
Qy 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
|||||||||||||||||||||||||||||||||||||||
Db 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
Conclusion
NO CLAIM IS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Schwabe et al. (US2019040130, as in IDS) teach a method of treating different diseases including multiple sclerosis ([0439]-[0442]), comprising administering to a subject in need thereof a therapeutically effective amount of an anti-TREM2 agonist antibody to induce one or more TREM2 activities including DAP12 phosphorylation, PI3K activation, increased expression of one more anti-inflammatory mediators and reduced expression of one or more pro-inflammatory mediations (see para. [0442])), wherein the anti-TREM2 agonist antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 201, which is 100% identical to instant SEQ ID NO:44, and a light chain comprising the amino acid sequence of SEQ ID NO:214, which is 100% identical to instant SEQ ID NO:47 recited in claim 29 (see the sequence alignment below; see para.[0027]; [0105]-[0128], [0261]; [0254]-[0279]; claim 40).
SEQ ID NO:44
BGB58142
(NOTE: this sequence has 9 duplicates in the database searched)
ID BGB58142 standard; protein; 452 AA.
XX
AC BGB58142;
XX
DT 21-MAR-2019 (first entry)
XX
DE Anti-TREM2 antibody HC region-mutant huIgG1 PSEG, SEQ ID 201.
XX
KW TREM2 protein; alzheimers disease; amnesia; antibody;
KW antibody production; antibody therapy; antiinflammatory; cancer;
KW cognitive disorder; colitis; cytostatic; dementia;
KW frontotemporal dementia; gastrointestinal-gen.; heavy chain;
KW immunoglobulin G1; immunoglobulin gamma 1; immunosuppressive;
KW multiple sclerosis; mutein; neuroprotective; nootropic;
KW prophylactic to disease; spinal cord injury; therapeutic;
KW traumatic brain injury; triggering receptor expressed on myeloid cells-2;
KW ulcerative colitis; vulnerary.
XX
OS Homo sapiens.
OS Unidentified.
OS Chimeric.
OS Synthetic.
XX
CC PN US2019040130-A1.
XX
CC PD 07-FEB-2019.
XX
CC PF 03-AUG-2018; 2018US-00054680.
XX
PR 03-AUG-2017; 2017US-0541019P.
PR 27-FEB-2018; 2018US-0636095P.
XX
CC PA (ALEC-) ALECTOR LLC.
XX
CC PI Schwabe T, Brown E, Kong P, Tassi I, Lee S, Rosenthal A;
CC PI Pejchal R, Nielson NP;
XX
DR WPI; 2019-13815K/17.
XX
CC PT New antibody useful in pharmaceutical composition for preventing,
CC PT reducing risk, or treating individual having disease, disorder or injury
CC PT including dementia, frontotemporal dementia, Alzheimer's disease,
CC PT cognitive deficit and memory loss.
XX
CC PS Claim 13; SEQ ID NO 201; 264pp; English.
XX
CC The present invention relates to a novel anti-triggering receptor
CC expressed on myeloid cells-2 (TREM2) antibody useful for preparing a
CC pharmaceutical composition. The pharmaceutical composition is used for
CC preventing, reducing risk or treating individual having disease, disorder
CC or injury includes dementia, frontotemporal dementia, Alzheimer's
CC disease, Nasu-Hakola disease, cognitive deficit, memory loss, spinal cord
CC injury, traumatic brain injury, multiple sclerosis, chronic colitis,
CC ulcerative colitis and cancer. The invention further provides: a nucleic
CC acid sequence encoding the antibody; a vector comprising the nucleic acid
CC ; an isolated host cell comprising the vector; a method of producing the
CC antibody that binds to TREM2; and an antibody comprising fragment
CC crystallizable (Fc) region. The present sequence represents a anti-TREM2
CC antibody heavy chain region (HC) comprising a mutant human immunoglobulin
CC gamma 1 (huIgG1 PSEG) P331S/E430G, which is used in the invention for
CC treating the above mentioned diseases.
XX
SQ Sequence 452 AA;
Query Match 100.0%; Score 2407; Length 452;
Best Local Similarity 100.0%;
Matches 452; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYAFSSQWMNWVRQAPGQRLEWIGRIYPGGGDTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYAFSSQWMNWVRQAPGQRLEWIGRIYPGGGDTNY 60
Qy 61 AGKFQGRVTITADTSASTAYMELSSLRSEDTAVYYCARLLRNQPGESYAMDYWGQGTLVT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGKFQGRVTITADTSASTAYMELSSLRSEDTAVYYCARLLRNQPGESYAMDYWGQGTLVT 120
Qy 121 VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL 180
Qy 181 QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEL 240
Qy 241 LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE 300
Qy 301 QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPS 360
Qy 361 RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK 420
Qy 421 SRWQQGNVFSCSVMHGALHNHYTQKSLSLSPG 452
||||||||||||||||||||||||||||||||
Db 421 SRWQQGNVFSCSVMHGALHNHYTQKSLSLSPG 452
SEQ ID NO:47
BGB58155
(NOTE: this sequence has 11 duplicates in the database searched)
ID BGB58155 standard; protein; 219 AA.
XX
AC BGB58155;
XX
DT 21-MAR-2019 (first entry)
XX
DE Anti-TREM2 antibody LC region-mutant huIgG1 PSEG, SEQ ID 214.
XX
KW TREM2 protein; alzheimers disease; amnesia; antibody;
KW antibody production; antibody therapy; antiinflammatory; cancer;
KW cognitive disorder; colitis; cytostatic; dementia;
KW frontotemporal dementia; gastrointestinal-gen.; immunoglobulin G1;
KW immunoglobulin gamma 1; immunosuppressive; light chain;
KW multiple sclerosis; mutein; neuroprotective; nootropic;
KW prophylactic to disease; spinal cord injury; therapeutic;
KW traumatic brain injury; triggering receptor expressed on myeloid cells-2;
KW ulcerative colitis; vulnerary.
XX
OS Homo sapiens.
OS Unidentified.
OS Chimeric.
OS Synthetic.
XX
CC PN US2019040130-A1.
XX
CC PD 07-FEB-2019.
XX
CC PF 03-AUG-2018; 2018US-00054680.
XX
PR 03-AUG-2017; 2017US-0541019P.
PR 27-FEB-2018; 2018US-0636095P.
XX
CC PA (ALEC-) ALECTOR LLC.
XX
CC PI Schwabe T, Brown E, Kong P, Tassi I, Lee S, Rosenthal A;
CC PI Pejchal R, Nielson NP;
XX
DR WPI; 2019-13815K/17.
XX
CC PT New antibody useful in pharmaceutical composition for preventing,
CC PT reducing risk, or treating individual having disease, disorder or injury
CC PT including dementia, frontotemporal dementia, Alzheimer's disease,
CC PT cognitive deficit and memory loss.
XX
CC PS Claim 13; SEQ ID NO 214; 264pp; English.
XX
CC The present invention relates to a novel anti-triggering receptor
CC expressed on myeloid cells-2 (TREM2) antibody useful for preparing a
CC pharmaceutical composition. The pharmaceutical composition is used for
CC preventing, reducing risk or treating individual having disease, disorder
CC or injury includes dementia, frontotemporal dementia, Alzheimer's
CC disease, Nasu-Hakola disease, cognitive deficit, memory loss, spinal cord
CC injury, traumatic brain injury, multiple sclerosis, chronic colitis,
CC ulcerative colitis and cancer. The invention further provides: a nucleic
CC acid sequence encoding the antibody; a vector comprising the nucleic acid
CC ; an isolated host cell comprising the vector; a method of producing the
CC antibody that binds to TREM2; and an antibody comprising fragment
CC crystallizable (Fc) region. The present sequence represents a anti-TREM2
CC antibody light chain region (LC) comprising a mutant human immunoglobulin
CC gamma 1 (huIgG1 PSEG) P331S/E430G, which is used in the invention for
CC treating the above mentioned diseases.
XX
SQ Sequence 219 AA;
Query Match 100.0%; Score 1137; Length 219;
Best Local Similarity 100.0%;
Matches 219; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVVMTQSPDSLAVSLGERATINCRSSQSLVHSNRYTYLHWYQQKPGQSPKLLIYKVSNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVMTQSPDSLAVSLGERATINCRSSQSLVHSNRYTYLHWYQQKPGQSPKLLIYKVSNRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTRVPYTFGQGTKLEIKRTVAAPSV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTRVPYTFGQGTKLEIKRTVAAPSV 120
Qy 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
Qy 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
|||||||||||||||||||||||||||||||||||||||
Db 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
March 5, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675