DETAILED ACTION
Examiner acknowledges receipt of the reply filed 9/15/2025, in response to the restriction requirement mailed 7/16/2025.
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 21-24, 30, 31, 58, 60, and 63 are pending. Claims 21, 31, 60, and 63 are withdrawn from further prosecution for the reasons set forth herein.
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 are being examined on the merits in this office 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 of Group 1 (claims 1-3, 6, 7, 12-14, 16, 18, 19, 21-24, 30, and 58) without traverse in the reply filed on 9/15/2025 is acknowledged.
Claims 18, 21, 31, 60, and 63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/15/2025.
Applicant’s election of the following representative in the reply filed on 9/15/2025 is acknowledged. Election was made without traverse.
flow modulator – VEGF-c
species of gene that is altered/assessed – Itga1, Elmo1, Sash1, Timp2, Socs5, Apoe, Reln, Abca1, Bsg, Adam10
neurological therapeutic agent – antibody/fragment that binds to amyloid beta
species of neurological disease- Alzheimer’s
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 read on the elected species.
Claim 21 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/15/2025.
In reply to this office action, the status identifiers of withdrawn claims should be revised.
Drawings
The drawings are objected to for the following reasons. For example, but not limited to, the shading of Figs 7B, 7C, 13D-13H, 16C, 18D, 20A, 20C, 21, etc makes it difficult to distinguish between different data points. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
At least Figs 15A and 14H/I refer to color fluorescence, green, blue, etc.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Claim Objections
Claims 1-3, 6, 7, 22-24, and 58 are objected to because of the following informalities:
Claim 1 should be amended to recite “a lymphatic endothelial cell (LEC), a brain myeloid cell (e.g., microglia (Mg)), an infiltrating leukocyte, , or a combination thereof in a subject in need thereof … thereby modulating the activity of the LEC, brain myeloid cell, Mg, infiltrating leukocyte, brain blood vascular cell, , or a combination thereof in the subject”.
Claims 2 and 13 should be amended to delete reference to tables 2-29 and to list the substituents therein (see MPEP 2173.05(s)). It is further noted that at least Table 18 summarizes results, as opposed to listing genes. Reference to Table 18 should be deleted.
It is further noted that bold font should be removed from claim 2, “Tables 2-29 ”.
Claim 3 should be amended to recite at line 4 “one or more genes[[,]]; or wherein the level of”.
Claim 6 recites the term “or” multiple times in the claim. Claim 6 should be amended to delete the first and second recitation of “or”. The claim should further amended to include either semicolons (;) or Roman numerals (i, ii, etc) to separate/distinguish the alternative claim limitations.
Regarding claim 7, it is unclear if the claim is intended to recite subgroupings of genes, or the listing is intended to recite one continuous list of genes. Claim 7 should be amended for clarification. Specifically, claim 7 recites multiple iterations of the term “and”. If the genes recited in claim 7 are intended to be one listing, then the claim should only recite “and” between the last two variables.
Further regarding claim 7, the phrase “and/or” should be deleted from the second to last line. The claim should instead recite “and a combination thereof”.
Claim 22 should be amended to recite “peptide that forms a pathological aggregate”.
Regarding claim 23, the acronym TDP43 referring to a protein/peptide should be written out in full name in the first appearance of the claims.
Claim 24 should be amended to delete the term “immunoglobulin” at lines 4 and 7. The term immunoglobulin is deemed to be redundant with the term antibody. The claim should be clarified if a specific type of immunoglobulin. Claim clarification is required.
Claim 24 should further recite “gosuranemab, armanezuma
Claim 58 recites acronyms that should be written out in full name in first order appearance, including but not limited to, PD, ALS, PANDAS. Claim 58 should further be amended to recite “dementia complex, or a combination thereof .
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 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.
The metes and bounds of claim 1 are deemed to be indefinite. The claim recites “modulating an activity” of a recited cell “wherein the activity is an alteration of gene expression in one or more genes”. The terms “alteration” or “modulation” does not give an indication whether a therapeutic effect is achieved when one or more genes is upregulated or downregulated compared to a control level, and if so, by how much this up- or down-regulation should be compared to the control levels for a therapeutic effect to be considered/obtained.
Regarding claim 1, the use of parenthetical phrases render the claims indefinite because it is unclear whether the limitations following the phrases or in parentheses are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 1, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 1 recites the limitation "the fluid flow". There is insufficient antecedent basis for this limitation in the claim.
Because claims 2, 3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 depend from indefinite claim 1and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
The skilled artisan is not apprised of the metes and bounds of claims 2 and 3. Claim 2 recites that there is an increase or decrease in the level of gene expression of one or more genes listed in tables 2-29. The tables recite hundreds of genes. Claim 3 recites percent and fold increase/decrease of gene expression for the one or more genes. The skilled artisan is not apprised of what specific genes are expected to increase or decrease, much less by what level in order to provide a therapeutic effect sufficient for “modulating the activity” of a recited cell.
The metes and bounds of claim 6 are deemed to be indefinite. Claim 6 recites: The method of claim 2, wherein the control level is a level of the gene expression of the one or more genes in a healthy subject not having a neurological disease, or wherein the control level is an average level of gene expression of the one or more genes in a population of healthy subjects not having a neurological disease, or wherein the control level is a level of the gene expression of the one or more genes in an age-matched subject with intact and functional meningeal lymphatic vasculature and no underlying neurological disease, or wherein the control level is an average level of gene expression of the one or more genes in a population of age-matched subjects with intact and functional meningeal lymphatic vasculature and no neurological disease. The skilled artisan is not apprised of claim elements that fall within the claim scope and those that fall outside the claim scope, due to alternative claim language and multiple recitations the term “or”.
Examiner recommends that the first and second recitations of “or” be deleted from the claim. The claim should further amended to include either semicolons (;) or Roman numerals (i, ii, etc) to separate/distinguish the alternative claim limitations.
Further regarding claim 6, the control level or baseline of comparison is variable for each gene. This renders the claim indefinite because there is no single defined baseline for each gene. The baseline becomes arbitrary given the hundreds of genes that fall within the claim scope and the numerous “control levels” that could be given to any gene. The skilled artisan is not apprised of the definitive metes and bounds of the claim scope.
The metes and bounds of claim 7 are deemed to be indefinite. The claim recites multiple iterations of the term “and”, as well as the term “and/or” in the second to last line of the claim. The skilled artisan is not apprised of claim elements that fall within the claim scope and those that fall outside the claim scope, due to alternative claim language. It is unclear from claim 7, if the intended claim scope is to be one continuous listing of genes. Under a second claim interpretation, claim 7 recites separate subgroups of genes, e.g., ll. 3-5 is one group, l. 6 is a second group, l. 7 is third group, etc. Claim clarification is required to further define the claim scope.
Claim 22 recites “protein or peptide that forms pathological aggregate”. While features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus (or composition) must be distinguished from the prior art in terms of structure rather than function. In re Schreiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997).
The metes and bounds of claim 24 are deemed to be indefinite. The following pertains to the first clause of the claim - amyloid beta- but also applies to clauses for tau and alpha-synuclein.
the protein is amyloid beta, and wherein the antibody or the antigen binding fragment thereof is selected from the group consisting of: bapineuzumab, gantenerumab, aducanumab, solanezumab, immunoglobulin, BAN2401, semorinemab, zagotenemab, crenezumab, and the antigen binding fragment thereof or the antibody or the antigen binding fragment thereof comprises a HCDR1, a HCDR2, a HCDR3, a LCDR1, a LCDR2, and a LCDR3 of any one of bapineuzumab, gantenerumab, aducanumab, solanezumab, immunoglobulin, BAN2401, semorinemab, zagotenemab, crenezumab, or an antigen binding fragment thereof;
The skilled artisan is not apprised of claim elements that fall within the claim scope and those that fall outside the claim scope, due to alternative claim language and multiple recitations the terms “and” and “or”. For instance, but not limited to, it is unclear if the claim scope is intended to read on an antibody binding fragment of an antibody binding fragment thereof, e.g., a fragment of a Fc fragment. Claim clarification is required.
Claim 58 recites the limitation "the neurological disease". There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 58, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The phrase "such as" is recited three times in claim 58.
The use of parenthetical phrases in claim 58 render the claims indefinite because it is unclear whether the limitations following the phrases or in parentheses are part of the claimed invention.
Claim 58 recites “two or more of any listed items”. It is unclear from the claim as to what is intended by “listed items”.
Examiner recommends that claim 58 be amended to recite “dementia complex, or a combination thereof
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 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 1 is drawn to method of modulating an activity of a lymphatic endothelial cell (LEC), a brain myeloid cell (e.g., microglia (Mg)), an infiltrating leukocyte, and/or a brain blood vascular cell (e.g., a brain blood endothelial cell (bBEC)) in a subject in need thereof, wherein the activity is an alteration of gene expression in one or more genes, the method comprising a flow modulator and neurological therapeutic. Claim 2 recites wherein the alteration of gene expression is an increase/decrease of a gene listed in Tables 2-29. The tables appear to recite hundreds of different genes, any of which can have an increased or decreased expression. Claim 3 recites levels of increase/decrease in gene expression, e.g. 50%, 75%, 100%, 1.25x, 1.5x, 1.75x or 2x. Claim 6 recites different levels of comparison/baseline for gene expression. Claim 7 recites approximately 200 different genes.
Claims 18 and 30, recite that the flow modulator comprises a VEGF3 agonist or a FGF2, wherein the VEGFR3 agonist comprises VEGF-c. Claims 12, 19, and 21-24, are drawn to the neurological therapeutic agent comprises small molecule, a nucleic acid, a peptide, a protein, an antibody or antigen binding fragment thereof, a recombinant virus, a vaccine, and a cell.
The USPTO provides claim terms with broadest reasonable interpretation in light of the specification.
The instant specification defines “flow modulator” [PGPUB 0247]:
As used herein. “flow modulators” shall be given its ordinary meaning and shall also broadly refer to classes of compositions that can increase or decrease the passage of substances into and out of meningeal lymphatic vessels, and thus can modulate flow in CSF and ISF, and/or, can modulate immune cell migration within, into, and out of the meningeal lymphatic vessels.
The instant specification states [PGPUB 0026]
the neurological therapeutic agent comprises an agent selected from the group consisting of a small molecule, a nucleic acid, a peptide, a protein, an antibody, a recombinant virus, a vaccine, and a cell.
The genus of genes encompasses hundreds of genes – with variable up- or down-regulation, that is compared to a control level/baseline that is not explicitly defined. The level of gene alteration necessary to elicit activity of a recited cell is unclear.
Assessment of whether species are support in the original specification
The instant specification discloses the flow modulator (VEGF-c) and neurological therapeutic agent (aducanumab) had the claimed function of altering gene expression, and reducing aggregation of amyloid beta. See Ex 7, 10-11.
There was no disclosure of other flow modulators or neurotherapeutic agents that had the claimed function.
In summary, for these reasons, the skilled artisan would reasonably conclude that the inventor(s), at the time the application was filed, had possession of VEGF-c and aducanumab at the time the invention was filed.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the disclosure of VEGF-c and the amyloid beta antibody aducanumab [full-length antibody] is not representative of the genus of flow modulator and neurological therapeutic agents thereof because the genus is large.
Identifying characteristics and structure/function correlation
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe the structural, physical and/or chemical properties of flow modulator, and neurological therapeutics that have the claimed functions.
The genus of genes encompasses hundreds of genes – with variable up- or down-regulation, that is compared to a control level/baseline that is not explicitly defined. The level of gene alteration necessary to elicit activity of a recited cell is unclear. This is further complicated by the diversity of diseases that fall under the term “neurological disease” having variable etiologies, affecting different patient populations. It is unclear from the specification as to what genes correlate with different neurological diseases.
In conclusion, for the reasons presented above, the skilled artisan would reasonably conclude that the inventors, at the time the application was filed had full possession of the flow modulators and the neurological therapeutic agent, in a subject with subject with Alzheimer’s disease.
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.
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Kipnis et al. (WO2017210343- cited in IDS filed 1/09/2023)), as further evidenced by Da Mesquita et al (Nature 560: 25-191 (Aug 2018- cited in IDS filed 1/09/2023), in view of Sevigny et al. (Nature 537: 50-56 (2016)).
Kipnis and Da Mesquita are both named authors of Da Mesquita et al journal article.
Kipnis et al. teach a method for increasing flow of fluid in the central nervous system of a subject comprising VEGFR3 agonist [flow modulator] (claim 1 and Abstract). Kipnis et al. teach a method of treating Alzheimer’s comprising administering to the subject a therapeutically effective amount of VEGF-c into the cerebrospinal fluid (e.g., paras. [0167]-[0168], Ex 8). Kipnis et al. teach and claim reducing amyloid beta plaques in a subject comprising administering a VEGFR3 agonist to the meningeal space (claim 20). Kipnis et al. claim a method of increasing clearance of a molecule from the CNS comprising administering VEGFR3 agonist to the meningeal space of the subject (para. [0010], claim 33). Kipnis et al. discloses VEGF-c expression in the CNS or a mouse model of AD ameliorated dementia symptoms ([0046], [0179], [0189]-[0190]; Fig 34A-C). Kipnis et al. teach a method reducing the number and/or volume of amyloid plaques (para. [0140]). Kipnis et al. teach that injection of VEGF-c results in increase in diameter of the meningeal lymphatic vessels (para. [0154]).
Da Mesquita et al also disclose the treatment of Alzheimer’s disease with VEGF-c and now it enhances meningeal lymphatic drainage macromolecules from the cerebrospinal fluid, improving brain perfusion and learning/memory performance (abstract, pp. 185-190). The reference discloses RNA sequence analysis of meningeal lymphatic vessels (lymphatic endothelial cells; LECs) and shows differential expression of 607 in meningeal LECs of older mice compared to the young mice (p. 187, Fig 2). Da Mesquita et al indicates that VEGF-c may be administered by gene therapy, e.g. delivered by an adenoviral vector (p. 188; methods). Da Mesquita et al disclose that ageing is the principal risk factor for many neurological disorders, including Alzheimer’s disease, and has a detrimental effect on CSF and ISF paravascular recirculation within the brain (abstract; pp. 187, 189). The reference discloses that aging is also associated with peripheral lymphatic dysfunction and that deterioration of meningeal lymphatic vessels underlies some aspects of age-associate cognitive decline (abstract; pp. 185, 187-190). The reference discloses a correlation between aging and differential expression in certain genes in meningeal LECs (methods, pp. 187-190; Fig 2, extended data Fig 5).
Thus, Kipnis et al. and Da Mesquita et al teach that VEGF-c can be used to treat Alzheimer’s disease. Administration of VEGF-c further enhances meningeal lymphatic drainage fluid flow in the central nervous system. Alzheimer’s and aging were associated with differential expression in LECs.
Kipnis et al. and Da Mesquita et al do not teach administering an effective amount of a neurological agent to the CNS of the subject. However, the teachings of Sevigny et al. cures this deficiency.
Sevigny et al. teach aducanumab human monoclonal antibody that selectively targets aggregated amyloid beta (Abstract). Sevigny et al. teach monthly IV infusions of aducanumab reduced amyloid beta in a time and dose dependent manner accompanied by a slowing of clinical decline (Abstract, Table 1, Figure 1-4). Sevigny et al. teach aducanumab was shown to enter the brain (Abstract).
It would have been obvious to one or ordinary skill in the art at the time of the invention to combine VEGF-c from Kipnis et al. and aducanumab from Sevigny et al. for treatment of AD and clearance of aggregated amyloid plaques. MPEP 2144.06 states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In the instant case, Kipnis et al. teach VEGF-c for treatment of AD and clearance of amyloid beta plaques and Sevigny et al. teach aducanumab for treatment of AD and clearance of amyloid beta plaques, therefore the prior art teaches the compositions useful for the same purpose. A reasonable expectation of success is expected given that each component (VEGF-c ad aducanumab are treatments for AD and aggregated plaque clearance in AD).
With respect to the limitations of “modulating an activity” of a recited cell wherein “the activity is alteration of gene expression in one or more genes”, the combination of Kipnis et al. and Sevigny et al. would necessarily have all of the activities and properties of the composition of claim 1. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
It is further noted that the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
In other words, Kipnis et al. and Sevigny et al. make obvious administering a flow modulator (VEGF-c) and Sevigny et al. teach administering a neurological therapeutic agent (aducanumab) to a subject with AD. Therefore administering the same composition to the same patient population would necessarily result in an alteration of gene expression in one or more genes in a recited cell, e.g., LECs, as instantly claimed.
Accordingly, claims 1-3, 6, and 7 are rendered obvious. Regarding claims 6 and 12, Da Mesquita et al teach methods for assessing gene expression in Alzheimer’s animal model (methods).
Regarding claim 13, Kipnis et al teach selecting a subject that has a neurological disease or is at risk for developing a neurological disease (e.g., paras. [0064], [0091]-[0098]). Regarding claims 14, 16, and 58, Kipnis et al teach that the neurological disease is Alzheimer’s disease (e.g., paras. [0091], [0096], [0105], [0140], [0167]-[0168]; Example 11, claim 3, Figs 34A-c). Da Mesquita et al teach patients with Alzheimer’s disease, as well a mouse model. See article generally. Further regarding claim 58, the neurological diseases include multiple sclerosis, ALS, Parkinson’s disease (e.g., Kipnis et al at paras. [0064], [0167]).
Regarding claim 18, Kipnis et al. teach VEGF-c, which is a VEGFR3 agonist. With respect to claims 19 and 22-24, Sevigny et al. teach aducanumab is an antibody that binds amyloid beta. Kipnis et al. and Sevigny et al. teach amyloid beta is associated with pathological aggregate. Regarding claim 30, VEGF-c was administered via intra-cisterna magna injections (Kipnis et al at, e.g., Examples 5-6, 11; Da Mesquita- methods). Sevigny et al. teach that the amyloid beta antibody was administered systemically (pp. 52 and 55).
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 are obvious in view of the teachings of the cited references.
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.
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Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, 23, 25, 26, 28, 30, 31, and 65 of copending Application No. 17/766479 (hereinafter the ‘479 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1-3, 6, 7, and 12, claims 1 and 25 of the ‘479 application recites a method of: (1) increasing clearance of amyloid beta (Aβ) or an amyloid precursor protein from the central nervous system in a subject in need thereof; (2) reducing an aggregate of a amyloid beta (Aβ) in the central nervous system of a subject in need thereof; (3) reducing a microglial inflammatory response in the central nervous system of a subject in need thereof; (4) reducing neurite dystrophy in the central nervous system of a subject in need thereof; or (5) treating a neurological disease in a subject in need thereof, wherein the subject has a neurological disease or disorder associated with accumulation of amyloid plaques, the method comprising: administering an effective amount of a flow modulator to a meningeal space of the subject, wherein the flow modulator comprises a VEGF-c or a polynucleotide encoding the VEGF-c; and administering an effective amount of a neurological therapeutic agent to the central nervous system of the subject, wherein the neurological therapeutic agent comprises an antibody that binds to amyloid beta (Aβ), or an antigen binding fragment thereof, thereby increasing the clearance of the amyloid beta (Aβ) or amyloid precursor protein from the central nervous system of the subject, reducing the aggregate of the amyloid beta (A) in the subject, reducing the microglial inflammatory response in the central nervous system of the subject, reducing neurite dystrophy in the central nervous system of the subject, or treating the neurological disease in the subject. Claim 25 recites that the neurological diseases Alzheimer’s disease.
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
The claims of the ‘479 application to not expressly teach a method of modulating an activity of a recited cell wherein the activity is an alteration of gene expression in one or more genes. However, claims of the ‘479 application do recite the same method steps: administering the same therapeutic combination- flow modulator (VEGF-c) and neurological therapeutic agent (amyloid beta antibody), route of administration (to the CNS), and patient population (neurological disease, AD). Because the methods steps are the same, the claims of the ‘479 application inherently teach the same process of modulating an activity, e.g., alteration of gene expression of one or more genes in the claim cells. Accordingly, the claims rendered obvious.
Regarding claims 14, 16, and 58, claim 25 of the ‘479 application recites that the neurological disease is Alzheimer’s disease.
Regarding claim 18, claims 1 and 65 of the ‘479 application recite that the flow modulator is VEGF-c.
Regarding claims 19, 22, 23, and 24, claim 19 of the ‘479 application recites that the antibody or the antibody binding fragment is selected from bapineuzumab, gantenerumab, aducanumab, solanezumab, immunoglobulin, BAN2401, semorinemab, zagotenemab, crenezumab, and an antigen binding fragment thereof- antibodies that bind amyloid beta (reads on protein that causes pathological aggregate).
Regarding claim 30, claim 1 of the ‘479 application recite that flow modulator (VEGF-c) is administered to the meningeal space, and of the neurological therapeutic agent (Ab that binds amyloid beta) is administered to the CNS. Claims 26, 28, 30, and 31 of the ‘479 application recite routes of administration, and dosing times (consecutive, concurrently).
Accordingly, claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 are rendered obvious.
Conclusion
No claims are allowed.
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 21-24, 30, 31, 58, 60, and 63 are pending. Claims 21, 31, 60, and 63 are withdrawn.
Claims 1-3, 6, 7, 12-14, 16, 18, 19, 22-24, 30, and 58 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654