DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 34-44) in the reply filed on 11/26/2025 is acknowledged. The traversal is on the ground(s) that the examination of Group III can be performed with Group I without undue search burden on the examiner. This is not found persuasive because the restriction practice is performed under PCT Rule 13.1 which based on sharing special technical feature and not the search burden as in US Applications.
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 34-44 and 51-53 are pending.
51-53 are withdrawn for being drawn to non-elected inventions (i.e., Groups III).
Claims 34-44 are under examination.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 8/21/2023, 3/7/2025, 4/22/2025, and 9/26/2025 have been considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The instant application is a 371 of PCT/JP2020/025313 filed on 6/26/2020.
Claim Objections
Claim 41 is objected to because of the following informalities: claim 41 is objected for the use of an abbreviated phrases (iPS cells, ES cells), which should be described for the first time followed by an abbreviated form placed in a bracket. . 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.
Claim 36 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 36, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. The term “optionally modified” is broadly interpreted that it does not have to occur. Therefore, metes and bounds of the claim is cannot be determined. See MPEP § 2173.05(d).
Claim 42 recites the limitation "the Fc" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 42 is drawn to a method according to claim 34 using a product by process claim. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 34, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chung et al. (US 2016/0137707).
The instantly claimed invention is broadly drawn to a method for inducing the formation of the presynaptic apparatus in mammalian neurons by co-culturing the neurons with a microbead, wherein at least one Leucine-rich repeat transmembrane neuronal protein (LRRTM) molecule selected from the group consisting of LRRTM family molecules or a fusion protein containing the LRRTM molecule is fixed to the surface of the microbead, and wherein the LRRTM molecule or the fusion protein containing the LRRTM molecule is fixed to the surface of the microbead via a linker.
Chung et al. teach a formation of presynaptic apparatus (complex) in mammalian neurons by co-culturing the neurons with a microbead, wherein a synaptogenic protein comprises a biotin tag at the C-terminal, wherein the synaptogenic protein is leucine-rich repeat transmembrane protein (LRRTM) and wherein the synaptogenic protein comprises a fluorescent tag and it further comprises a His-tag (see claims 1-6, 11-12). They teach that the protein is attached to the surface of a microbead (claim 9).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 34-40, and 42-44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (US 2016/0137707) in view of de Wit et al. (IDS, Neuron, 2009, 64: 799-806) and JP 20175226377 (9/14/2017).
The instant invention is broadly drawn to a method for inducing the formation of the presynaptic apparatus in mammalian neurons by co-culturing the neurons with a microbead, wherein at least one Leucine-rich repeat transmembrane neuronal protein (LRRTM) molecule selected from the group consisting of LRRTM family molecules or a fusion protein containing the LRRTM molecule is fixed to the surface of the microbead, and wherein the LRRTM molecule or the fusion protein containing the LRRTM molecule is fixed to the surface of the microbead via a linker, wherein LRRTM is fusion protein with an IgG Fc (claim 35), wherein the linker is selected from a protein, PEG, modified sugar chain and a nucleic acid having a length of 10 nm or more (claim 36), wherein the neurons are human central neurons or human central neurons or human glutamatergic neurons and LRRTM is LRRTM2.
Chung et al. teach a formation of presynaptic apparatus (complex) in mammalian neurons by co-culturing the neurons with a microbead, wherein a synaptogenic protein comprises a biotin tag at the C-terminal, wherein the synaptogenic protein is leucine-rich repeat transmembrane protein (LRRTM) and wherein the synaptogenic protein comprises a fluorescent tag and it further comprises a His-tag (see claims 1-6, 11-12). They teach that the protein is attached to the surface of a microbead (claim 9). Chung et al. do not teach that LRRTM is LRRTM2 and they do not teach a fusion of protein of LRRTM with an Fc.
de Wit et al. teach that LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation which results in presynaptic differentiation (see Summary, pg. 799). They teach that LRRTM2 localizes to excitatory synapses in transfected hippocampal neurons and induces presynaptic differentiation via the extracellular LRR domain (Summary). They teach using human LRRTM2 with GFF in the assay. They teach attaching an Fc with LRRTM2 by make LRRTM2-ecto-Fc for determining LRRTM2 binding to rat brain and using immunostaining to visualize LRRTM2 in a synaptically-localized protein (see pg. 5, 2nd and 3rd paragraphs). Regarding the limitation of claim 36, the length of a linker can be optimized by on skill in the art which can be about 10 nm or more and that the art of optimizing a linker so that LRRTM2 does not interfere with binding of cognate receptor or partner is well known (see Ma et al. PLOS|one, 2014,9: e112292, page 1-10, Table 1, PEG linkers and properties). It is noted that the reference Ma et al. is applied to support the skill of the art and not as a prior art. Regarding claims 37-39, they do not use human neurons to study the effect of LRRTM2 for inducing formation of presynaptic neurons but they did use hippocampal neurons to study and JP 2017526377 teaches to use human neurons for in vivo assays. JP 2017526377 teaches that human neurons include sympathetic neurons, central nervous system neurons, GABAnergic neurons, glutamatergic neurons, cholinergic neurons, an adrenergic neuron and a trigeminal neuron.
Therefore, it would have been prima facie obvious to one ordinary skill in the art at the time the invention was made to use to expect the similar result when used with human neurons or glutamatergic neurons, or central nervous system neurons in the assay for inducing presynaptic complex (apparatus) as taught by Chung et al using LRRTM-fc as taught by de Wit et al. Additionally, one would have been motivated to do so because JP 2017526377 teaches that human neurons or central nervous system neurons or glutamatergic neurons can be used in in vitro culture and assays for screening of pharmacological agents. Further, one would have a reasonable expectation of success in using human neurons or functionally equivalent central nervous system neurons or glutamatergic neurons as taught by JP 2017526377. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
Claim(s) 41 is rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (US 2016/0137707) in view of de Wit et al. (IDS, Neuron, 2009, 64: 799-806) as applied to claims 34-40, and 42-44 above, and further in view of Kondo et al. (IDS, The 45th annual meeting of the Japanese Soc. of Toxicology at Osaka International Convention Center, 2018).
The instantly claimed invention is broadly drawn to a method for inducing the formation of the presynaptic apparatus in mammalian neurons by co-culturing the neurons with a microbead, wherein at least one Leucine-rich repeat transmembrane neuronal protein (LRRTM) molecule selected from the group consisting of LRRTM family molecules or a fusion protein containing the LRRTM molecule is fixed to the surface of the microbead, and wherein the LRRTM molecule or the fusion protein containing the LRRTM molecule is fixed to the surface of the microbead via a linker, wherein the neurons are neurons from differentiated human iPS or human ES cells.
The teachings of Chung et al and de Wit are summarized above. Neither Chung et al. nor de Wit et al teach that the neurons are from iPS or ES cells.
Konda et al. teach that human iPS cells can be differentiated into neurons and that the differentiated neurons can be used in in vitro assays.
Therefore, it would have been prima facie obvious to one ordinary skill in the art at the time the invention was made to use iPS cells as taught by Konda et al as a substitute to human neurons or glutamatergic neurons, or central nervous system neurons in an assay for inducing presynaptic complex (apparatus) as taught by Chung et al and JP 2017526377 to induce the formation of a presynaptic complex using LRRTM-fc as taught by de Wit et al. Additionally, one would have been motivated to do so because Konda et al teach that human iPS can differentiate into neurons that can be used in in vitro culture and assays for screening of pharmacological agents. Further, one would have a reasonable expectation of success in using human iPS that can differentiate into neurons for an assay determine if LRRTM2 can induce presynaptic complex because Konda et al teach that human iPS can differentiate into a neuron. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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