DETAILED ACTION
Claims 13, 17-19 and 24-56 were/stand cancelled. Claims 1-12, 14-16, 20-23 and 57 are pending.
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 .
Priority
This application is a 371 of PCT/US2022/045909 (10/06/2022) which claims benefit of 63/252,985 (10/06/2021) as reflected in the filing receipt issued on August 20 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 19 2024 are is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to for the following reasons:37 CFR 1.84 (u)(1) states “Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter.”
In the current case, the view numbers for the partial views for Figures 12 that appear on several sheets are followed by "Cont." instead of a capital letter such as FIG. 12A, FIG. 12B, etc.
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.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See Table 3.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claim 1 is objected to because of the following informalities: The acronym “PEG” is not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “PEG” is interpreted to mean polyethylene glycol. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: the acronym “DOPE” and “cKK-E12” are not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “DOPE” is interpreted to mean 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine. The abbreviation cKK-E12 is intended to mean:
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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 8-11, 15-16 and 57 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 8-10 and 15-16 as currently written are vague and indefinite. The claims depend from claim 0 which does not exist. In the interest of compact prosecution the claims are interpreted as depending from claim 1.
Claims 11 and 57 are included in the rejection as they depend on a rejected base claim and they do not clarify the issues.
Claim Rejections - 35 USC § 112-Scope of Enablement
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.
Claim 23 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating diseases associated with inflammatory microglial, does not reasonably provide enablement for treating or preventing any disease, any disorder or any condition in a subject in need thereof with any agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The breadth of the claims and Nature of the Invention
The claim is very broad insofar as it recites treating or preventing any disease, disorder or condition with any agent and lipids selected from: (a) an ionizable amino lipid, (b) a sterol, (c) a phospholipid and (d) a PEG-lipid. This is interpreted as requiring a lipid from each of (a), (b), (c) and (d). Looking to the instant specification, specifically paragraph 00284 (page 108) states that Agents that are delivered by the systems (e.g., pharmaceutical compositions) described herein may be (e.g., therapeutic or prophylactic), diagnostic, cosmetic, or nutraceutical agents. In some embodiments, the agent is an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, an immunological agent, or an agent useful in bioprocessing (e.g., intracellular manufacturing of proteins, such as a cell's bioprocessing of a commercially useful chemical or fuel).
Thus, the BRI of the claim is using any chemical which could be for example a diagnostic agent in a mixture of lipids to treat or prevent any disease, disorder or condition. This is an extremely broad scope.
The Relative Skill Level, the State of the Prior Art and The Level of
Predictability in the Art
The relative skill of those in the art is high, that of an MD or PHD someone with experience in pharmacy/pharmacology and drug design as well as medicine.
Challener (pharmaceutical Technology 2025) teaches that while LNPs (lipid nanoparticles) are the go-to solution for delivery of nucleic acids, there is significant room for higher-performing alternatives, as LNPs face several limitations that impact their effectiveness as drug delivery systems. These issues include poor stability, limited loading capacity for drug substances, manufacturing process scale-up challenges, and the small number of approved lipid excipients available for LNP formulation. LNP instability is a particular concern. These LNPS are also subject to rapid clearance from circulation, reducing their bioavailability. LNPs suffer from challenging extra hepatic delivery. Achieving effective endosomal escape and intracellular delivery remains a significant challenge, limiting the successful release of therapeutic cargo into target cells (see limitations of LNPs section).
Langtree provides a list of currently incurable diseases and conditions. This information provides a comprehensive overview of diseases currently considered incurable, spanning a wide range of conditions including infectious, non-infectious, neoplastic, autoimmune, genetic, and metabolic disorders. The list includes both terminal illnesses, such as late-stage cancer and AIDS, and chronic conditions like diabetes, asthma, and Alzheimer's disease, which can often be managed but not cured. Many incurable conditions, including diabetes, asthma, and Parkinson's disease, can be managed for a lifetime through therapy and daily care.
Langtree, therefore teaches, while many conditions can be treated or managed, prevention is not so widely considered as possible.
The amount of direction or guidance provided and the presence or absence of working examples
Looking to the instant specification, firstly, instant claim 1, indicates that the composition (agent and lipids) selectively delivers an agent to a cell wherein the cell is a microglial cell. This is also supported in example 1 which states the use of lipid nanoparticles encapsulating therapeutic cargo as a novel drug delivery vehicle for selective uptake in microglia. Example 3 teaches that of the screened candidates, all LNP containing an ionizable lipid achieved significant levels of luciferase expression in iPS microglia. Delivery to inflammatory microglia is of interest for treatment of AD (Alzheimer’s disease). Several formulations exhibited losses in delivery efficacy in inflammatory conditions (also references FIGS. 2B, 2F, 6-10, 19A and 19B). Taught is there may be preferential uptake and transfection of inflammatory microglia compared to astrocytes.
Therefore, the specification makes it clear that the lipids can be used to deliver agents to the microglial and thus would be useful in treating diseases associated with inflammatory microglial such as AD, the specification does not teach how any disease or disorder or condition can be treated with any agent by administering the LNP via any administration route as contemplated by the instant claims. Since the specification contemplates selective delivery of an agent to a microglial cell, the specification does not teach how diseases such as diabetes can be treated with an agent and lipids as claimed (as diabetes is a diseases not associated with inflammatory microglial).
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed agents could be predictably used to treat or prevent the full scope of diseases, disorders or conditions as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12, 14-16, 20-23 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Heartlein et al. (EP3871696) in view of Pham et al. (Nanomedicine, 2020).
Applicant Claims
The instant application claims a method of selectively delivering an agent to a cell, comprising contacting the cell with a composition comprising an agent and lipids selected from: (a) an ionizable amino lipid, (b) a sterol, (c) a phospholipid, and (d) a PEG-lipid; wherein the cell is a microglial cell.
The instant application claims a method of treating or preventing a disease, disorder, or condition in a subject in need thereof, comprising administering to the subject a composition comprising an agent, and lipids selected from: (a) an ionizable amino lipid, (b) a sterol, (c) a phospholipid, and (d) a PEG-lipid.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Heartlein et al. is directed to lipid formulations for delivery of messenger RNA. Claimed is a composition comprising an mRNA encoding a therapeutic protein encapsulated within a liposome for use in a method of treating a disease or disorder comprising administering to a subject in need of treatment the composition;wherein the composition is injected intradermally, intramuscularly, or subcutaneously or administered intrathecally, intraventricularly, or intravenously and expression of the protein encoded by the mRNA is detectable in the liver, kidney, heart, spleen, serum, brain, skeletal muscle, lymph nodes, skin, and/or cerebrospinal fluid and the liposome comprises a cationic lipid and further a non-cationic lipid, a cholesterol-based lipid and a PEG-modified lipid wherein the molar ratio of cationic lipid to non-cationic lipid to cholesterol-based lipid to PEG-modified lipid is 30-50:25-35:20-30:1-15 (claim 1). A specific cationic lipid is cKK-E12:
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claim 7). A specific combination for the liposome claimed is cKK-E12, DOPE, cholesterol and DMG-PEG2K wherein DOPE is (1,2-dioleyl-sn-glycero-3-phosphoethanolamine). Additional PEG-modified lipids comprise a poly(ethylene) glycol chain of up to 5 kDa in length covalently attached to a lipid with alkyl chain(s) of C6-C20 length (claim 8). DMG-PEG2K is dimyristoylglycerol (paragraph 0012). Noncationic lipids include: DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (claim 8). The percentage of the non-cationic lipid may be about 25 to about 35% (paragraph 0063). The concentration of the cholesterol based lipid can be greater than 20% (paragraph 0064). The invention can be used to deliver mRNA at various doses ranging from about 0.1 to 5 mg/kg body weight (paragraph 0117). It is taught that during the preparation cationic liposomes may associated with the mRNA through electrostatic interactions (paragraph 0102).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Heartlein et al. teaches compositions comprising the same lipids, agent (mRNA) and claims intrathecal delivery as well as delivery to a cerebral spinal fluid, Heartlein et al. does not expressly teach administration to a microglial. However as recognized by Pham et al., siRNA-loaded nanoparticles were mainly taken up by spinal microglia, not be neurons or astrocytes, after intrathecal injection (page 1903, last paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 1 and 23, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the liposome with mRNA of Heartlein et al. via intrathecal injection. One skilled in the art would have been motivated to administer the liposomes in this manner as it is one of six specifically claimed routes of administration. Administration of the liposomes via intrathecal administration would have expected to result in the mRNA being delivered to a microglial cell as recognized by Pham et al.
Regarding the claimed ionizable amino lipid, cKK-E12 corresponds to the structure in claim 4 which contains the C10H21.
Regarding claims 5-9, Heartlein et al. expressly teaches the combination of cKK-E12:cholesterol:DOPE:DMG-PEG2K (aka a PEG-phospholipid).
Regarding claim 10, besides DMG-PEG2K, Heartlein et al. teaches PEG-modified lipids comprise a poly(ethylene) glycol chain of up to 5 kDa in length covalently attached to a lipid with alkyl chain(s) of C6-C20 length wherein lipids include: DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine. The use of DMPE (i.e. C14 lipid) with the PEG chain results in C14PEG2000.
Regarding claim 11 and 57, Heartlein et al. teaches suitable amounts for the cationic lipid, sterol, phospholipid and PEG-lipid. While the exact ratio is not disclosed by Heartlein et al., it is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05. Absent demonstration of the criticality, one skilled in the art would manipulate the amounts in order to achieve the desired level of encapsulation as well as delivery.
Regarding claim 12 and 14, Heartlein et al. expressly teaches an mRNA. Regarding claims 15-16, Heartlein et al. teaches suitable amount of CKK-E12 and mRNA. Furthermore, Heartlein et al. teaches that the mRNA interacts with the lipid via electrostatic interactions with the cationic lipid (aka CKK-E12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to manipulate the ratio of the CKK-E12 and mRNA in order to achieve the desired level of encapsulation. While the exact ratio is not disclosed by Heartlein et al., it is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05. Since Heartlein et al. clearly teaches suitable amounts of both the CKK-E12 and mRNA, absent demonstration of the criticality, it would have been obvious to one skilled in the art to determine the optimal ratio of the cationic lipid to mRNA.
Regarding claims 20-22, firstly as set forth above, intrathecal administration would be expected to result in delivery to the microglia. Since Heartlein et al. expressly teaches administration to treat a disease and as taught by Pham et al. excessive neuroinflammation often involves overactivation of microglia which leads to increased release and expression of inflammatory microglial mediators in the nervous disease. Neuropathic pain has been shown to result from chronic neuroinflammation and microglia contribute to this disease (page 1898, last paragraph). Therefore, intrathecal administration to a subject with neuropathic pain would be expected to be administering to an inflammatory microglial cell. As recognized by Pham et al. this method of administration results in uptake by spinal microglia, not be neurons or astrocytes. Since the lipids taught by Heartlein et al. are the same as instantly claimed, based on the claim language, it would be expected that the delivery is selective for the same cells as instantly claimed as these wherein clauses do not further limit the active method step(s) defined by the claim, namely contacting the cell. "A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."). Note MPEP 2111.04.
In this case, claims 20-22 uses the term "wherein", rather than "whereby", but it is concluded that the terms should be treated the same…the wherein clause does not inform the artisan of how the "contacting" steps are performed; rather, the wherein clause merely characterizes the results of those steps.
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 1-12, 14-16, 20-23 and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9629804 in view of Pham et al. (Nanomedicine, 2020).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a method of selectively delivering an agent to a cell, comprising contacting the cell with a composition comprising an agent and lipids selected from: (a) an ionizable amino lipid, (b) a sterol, (c) a phospholipid, and (d) a PEG-lipid; wherein the cell is a microglial cell.
The instant application claims a method of treating or preventing a disease, disorder, or condition in a subject in need thereof, comprising administering to the subject a composition comprising an agent, and lipids selected from: (a) an ionizable amino lipid, (b) a sterol, (c) a phospholipid, and (d) a PEG-lipid.
Patent ‘804 claims a method of delivery of messenger RNA (mRNA) in vivo comprising administering to a subject in of delivery a composition comprising an mRNA encoding a CFTR protein encapsulated within a liposome wherein the liposome comprises a cationic lipid. As claimed the cationic lipid is cKK-E12 (claim 2). DOPE is claimed (claim 4). Cholesterol and DMG-PEG2K are claimed. PEG-lipids are claimed (claim 3). DMPE is claimed (claim 13).
While Patent ‘804 claims administering to a subject the same composition, Patent ‘804 does not expressly claim to a microglial cell. However as recognized by Pham et al., siRNA-loaded nanoparticles were mainly taken up by spinal microglia, not be neurons or astrocytes, after intrathecal injection (page 1903, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘804 and Pham et al. and administer the composition via intrathecal injection. Patent ‘804 generally claims administration and intrathecal administration is one specific type of administration. Administration in this manner would expect to allow the composition to be taken up by microglial as taught by Pham et al.
Regarding claim 23, Patent ‘804 claims administering a mRNA encoding a CFTR protein, this reads on treating a disease, disorder or condition as claimed.
Regarding the claimed ratios of components, Patent ‘804 is silent. It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05.
Claims 1-12, 14-16, 20-23 and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10052284 in view of Pham et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘284 claims a method of treating cystic fibrosis comprising administering to a subject in need of treatment a composition comprising an mRNA encoding a CFTR protein encapsulated within a liposome wherein the liposome comprises a cationic lipid (claim 1). As claimed the cationic lipid is cKK-E12 (claim 2). DOPE is claimed (claim 4). Cholesterol and DMG-PEG2K are claimed (claim 6). PEG-lipids are claimed (claim 3). DMPE is claimed (claim 4).
While Patent ‘284 claims administering to a subject the same composition, Patent ‘284 does not expressly claim to a microglial cell. However as recognized by Pham et al., siRNA-loaded nanoparticles were mainly taken up by spinal microglia, not be neurons or astrocytes, after intrathecal injection (page 1903, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘284 and Pham et al. and administer the composition via intrathecal injection. Patent ‘284 generally claims administration and intrathecal administration is one specific type of administration. Administration in this manner would expect to allow the composition to be taken up by microglial as taught by Pham et al.
Regarding claim 23, Patent ‘284 claims treating cystic fibrosis.
Regarding the claimed ratios of components, Patent ‘284 is silent. It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05.
Claims 1-12, 14-16, 20-23 and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10959953 in view of Pham et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘953 claims a method of delivery of mRNA in vivo comprising administering to a subject in need of delivery a composition comprising an mRNA encoding an ASS1 protein wherein the liposome comprises a cationic lipid. As claimed the cationic lipid is cKK-E12 (claim 2). DOPE is claimed (claim 4). Cholesterol and DMG-PEG2K are claimed (claim 6) PEG-lipids are claimed (claim 3). DMPE is claimed (claim 13).
While Patent ‘953 claims administering to a subject the same composition, Patent ‘953 does not expressly claim to a microglial cell. However as recognized by Pham et al., siRNA-loaded nanoparticles were mainly taken up by spinal microglia, not be neurons or astrocytes, after intrathecal injection (page 1903, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘953 and Pham et al. and administer the composition via intrathecal injection. Patent ‘953 generally claims administration and intrathecal administration is one specific type of administration. Administration in this manner would expect to allow the composition to be taken up by microglial as taught by Pham et al.
Regarding claim 23, Patent ‘953 claims administering a mRNA encoding a ASS1 protein, this reads on treating a disease, disorder or condition as claimed.
Regarding the claimed ratios of components, Patent ‘953 is silent. It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05.
Claims 1-12, 14-16, 20-23 and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11890377. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘377 claims a method of delivery of mRNA in vivo comprising administering to a subject in need of delivery a composition comprising an mRNA that encodes Factor IX wherein said mRNA is encapsulated within a liposome and wherein the liposome comprises a cationic lipid (claim 1). As claimed the cationic lipid is cKK-E12 (claim 2). DOPE is claimed (claim 7). Cholesterol and DMG-PEG2K are claimed (claim 10). PEG-lipids are claimed (claim 6). DMPE is claimed (claim 7).
While Patent ‘377 claims administering to a subject the same composition, Patent ‘377 does not expressly claim to a microglial cell. However as recognized by Pham et al., siRNA-loaded nanoparticles were mainly taken up by spinal microglia, not be neurons or astrocytes, after intrathecal injection (page 1903, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘377 and Pham et al. and administer the composition via intrathecal injection. Patent ‘377 generally claims administration and intrathecal administration is one specific type of administration. Administration in this manner would expect to allow the composition to be taken up by microglial as taught by Pham et al.
Regarding claim 23, Patent ‘377 claims administering a mRNA encoding FIX, this reads on treating a disease, disorder or condition as claimed.
Regarding the claimed ratios of components, Patent ‘377 is silent. It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05.
Claims 1-12, 14-16, 20-23 and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10941395 in view of Pham et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘395 claims a method for inducing repair of a gene in a subject in need thereof, the method comprising administering to the subject one or more gRNA (reading on agent); a repair template and a Cas mRNA wherein the gRNA and repair template are provided in a lipid nanoparticle. The lipid nanoparticle comprises cKK-E12, DOPE, cholesterol, C14-PEG2000.
While Patent ‘395 claims administering to a subject the same composition, Patent ‘395 does not expressly claim to a microglial cell. However as recognized by Pham et al., siRNA-loaded nanoparticles were mainly taken up by spinal microglia, not be neurons or astrocytes, after intrathecal injection (page 1903, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘395 and Pham et al. and administer the composition via intrathecal injection. Patent ‘395 generally claims administration and intrathecal administration is one specific type of administration. Administration in this manner would expect to allow the composition to be taken up by microglial as taught by Pham et al.
Regarding claim 23, Patent ‘395 claims administering a mRNA encoding a CFTR protein, this reads on treating a disease, disorder or condition as claimed.
Regarding the claimed ratios of components, Patent ‘395 is silent. It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). NOTE: MPEP 2144.05.
Conclusion
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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636
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