DETAILED ACTION
Notice of 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 .
Requirement for an Election of Species
This application contains claims directed to the following patentably distinct species:
Elect a single method of treating a neurologic disorder in a patient by defining EACH of the following with specificity:
(1) Elect a single neurologic disorder (e.g., Parkinson’s disease, dementia with Lewy bodies, etc.);
(2) Elect a single transferrin receptor-targeting molecule (e.g., a single chain Fv antibody fragment, a single domain antibody fragment, a transferrin molecule, etc.); and
(3) Elect whether the cationic liposomal complex comprises a nucleic acid encoding an intrabody, or an intrabody.
The species are independent or distinct because claims to the different species recite the mutually exclusive characteristics of such species. In addition, these species are not obvious variants of each other based on the current record. Furthermore, there is an examination and search burden for these patentably distinct species due to their mutually exclusive characteristics. For example, the species require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search queries). Accordingly, Applicant is required under 35 U.S.C. 121 to (i) elect a single disclosed species for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable even though the requirement may be traversed (37 CFR 1.143); and (ii) identify the claims readable on the elected species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered non-responsive unless accompanied by an election. Currently, claims 1-2, 8-9 and 13 or claims 14-15, 21-22 and 26 are generic, depending on Applicant’s election of species above.
The election of the species may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species.
Should applicant traverse on the ground that the species are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the species to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
Telephonic Response to Requirement for an Election of Species
Applicant’s election without specifying traverse of a single method in the by telephone on 11/24/2025 is acknowledged as follows:
(1) As a single neurologic disorder – Applicant elects Parkinson’s disease.
(2) As a single transferrin receptor-targeting molecule – Applicant elects a single chain Fv antibody fragment; and
(3) Applicant elects the cationic liposomal complex comprises a nucleic acid encoding an intrabody.
The requirement is still deemed proper and is therefore made FINAL.
The elected species read upon claims 1-2, 4-5, 8-10 and 13. Claims 6-7, 14-15, 17-23 and 26 are 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.
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.
Claims 4 and 8 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 4 is drawn to the method of claim 1, “wherein the transferrin receptor-targeting moiety is…”. And claim 8 is drawn to the method of claim 1, “wherein the targeting moiety-targeted cationic liposomal complex is…”.
Claim 1 does not provide support for the recitations of “the transferrin receptor-targeting moiety” and/or “the targeting moiety-targeted cationic liposomal complex” of claims 4 and 8.
Claim 8 is drawn to the method of claim 1, wherein the targeting moiety-targeted cationic liposomal complex is administered via… “intraorgan (e.g., intrahepatic)…”
The phrase “e.g.” / “for example” renders the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
As such, claims 4 and 8 are rejected as indefinite.
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.
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 1-2, 4-5, 8-10 and 13 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lynch et al (J Mol Biol 377:136-147, 2008) in view of Chang et al (US 2020/0113829).
Claim 1 is drawn to a method of treating a neurological disorder in a patient (more specifically, Parkinson’s disease (claim 10)), comprising:
(a) providing a transferrin receptor-targeted cationic liposomal complex comprising:
a cationic liposome;
a transferrin receptor-targeting molecule that is complexed with (but not chemically conjugated to) the cationic liposome (more specifically, a single chain Fv antibody fragment (claim 4), even more specifically, an anti-transferrin receptor single chain Fv (TfRscFv) (claim 5)), wherein the transferrin receptor-targeting molecule does not comprise a lipid tag; and
a nucleic acid encoding an intrabody (more specifically, wherein the intrabody is a single chain FV antibody fragment (scFv) (claim 2)) against a protein associated with the neurological disorder; and
(b) administering the transferrin receptor-targeting cationic liposomal complex to the patient to treat the neurological disorder.
Lynch et al teach that the “[p]revention of abnormal misfolding and aggregation of α-synuclein (syn) protein in vulnerable neurons should be viable therapeutic strategies for reducing pathogenesis in Parkinson’s disease” (Abstract). Lynch et al further teach that “[a]n scFv intrabody against the nonamyloid component of α-synuclein [in particular, the anti-α-syn scFv intrabody “NAC32” (Abstract)] reduces intracellular aggregation and toxicity” (Title) and that “[s]uch intrabodies can serve as direct PD [Parkinson’s disease] molecular therapeutics” (Page 137, Column 2), wherein “delivery of the intrabody genes will require gene therapy” (Page 143, Column 2) “in which the intrabody gene is delivered to neurons… with proteins continuously synthesized” (Page 143, Column 2).
As such, Lynch et al teach a method of treating Parkinson’s disease comprising delivery of an anti-α-syn scFv intrabody gene. That is, Lynch et al teach a method of treating Parkinson’s disease comprising delivery of a nucleic acid that encodes an intrabody against a protein associated with the Parkinson’s disease, wherein the intrabody is a single chain FV antibody fragment.
However, Lynch et al do not teach the method wherein delivery of the nucleic acid comprises administration of a transferrin receptor-targeted cationic liposomal complex as claimed.
Yet, Chang et al teach “a method of treating a disease in a patient, comprising providing a ligand-targeted cationic liposomal complex [further referred to by Chang et al as a “nucleic acid delivery system” (Paragraph 0081)], comprising a cationic liposome, a targeting ligand that is complexed with the cationic liposome, but is not chemically conjugated with the cationic liposome, and wherein the targeting ligand does not comprise a lipid tag, and a nucleic acid and administering the ligand-targeted cationic liposomal complex… to the patient to the treat the disease” (Paragraph 0013), wherein “[s]uitably, the ligand is… an anti-transferrin receptor single chain Fv (TfRscFv)” (Paragraph 0020) and “the nucleic acid is gene, polynucleotide, such as plasmid DNA, DNA fragment…” and so on (Paragraph 0084). As further taught by Chang et al, the disease to be treated can be a neurologic disorder such as “Axonal & neuronal neuropathy (AMAN)... Chronic inflammatory demyelinating polyneuropathy (CIDP)… Multiple sclerosis… Neuromyelitis optica…” and so on (Paragraph 0077).
In view of all of the foregoing, it would have been prima facie obvious to carry out the method of Lynch et al for the treatment of Parkinson’s disease comprising administration of nucleic acid encoding an anti-α-syn scFv intrabody, wherein nucleic acid is delivered via a transferrin receptor-targeted cationic liposomal complex as claimed, with a reasonable expectation of success. It would have been obvious to do so considering that Lynch et al specifically state that the “delivery of the intrabody genes will require gene therapy” (Page 143, Column 2) and Chang et al teach the instantly claimed “ligand-targeted cationic liposomal complex” (Paragraph 0013) as a “nucleic acid delivery system” (Paragraph 0081) useful in the treatment of neurologic disorders.
Accordingly, claims 1-2, 4-5 and 10 are rejected as prima facie obvious.
Claim 8 is drawn to the method of claim 1, wherein the cationic liposomal complex is administered via intravenous (IV) administration.
Chang et al teach “the ligand-targeted cationic liposomal complex is administered via intravenous (IV)… administration” (Paragraph 0021).
Accordingly, claim 8 is also rejected as prima facie obvious.
Claim 9 is drawn to the method of claim 1, wherein the cationic liposomal complex crosses the blood-brain barrier, and the nucleic acid encoding the antibody is expressed in a neuronal cell.
As noted by the court in Hoffer v. Microsoft Corp. (405 F.3d 1326 (Fed. Cir. 2005)), a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (quoting Minton v. Nat ' l Ass ' n of Securities Dealers, Inc., 336 F.3d 1373 (Fed. Cir. 2003)).
In the instant case, the cationic liposomal complex crossing the blood-brain barrier and the nucleic acid encoding the antibody being expressed in a neuronal cell merely expresses the intended result of the prima facie obvious process of administering a nucleic acid encoding an anti-α-syn scFv intrabody via a transferrin receptor-targeted cationic liposomal complex as claimed.
As such, claim 9 is also rejected as prima facie obvious.
Claim 13 is drawn to the method of claim 1, wherein the cationic liposome comprises, for example, a mixture of dioleoyltrimethylammonium phosphate (DOTAP) and dioleoylphosphatidylethanolamine (DOPE) and/or cholesterol (chol).
Chang et al teach that “[a] wide variety of cationic liposomes are useful in the preparation of the complexes” wherein “[e]xamples of desirable complexes include those that comprise a mixture of dioleoyltrimethylammonium phosphate (DOTAP) and dioleoylphosphatidylethanolamine (DOPE) and/or cholesterol (chol)” (Paragraph 0089).
Accordingly, claim 13 is also rejected as prima facie obvious.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 4-5, 8-10 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 7,780,882 in view of Lynch et al (J Mol Biol 377:136-147, 2008).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘882 claims are drawn to a method of preparing an antibody- or antibody fragment-targeted cationic immunoliposome complex comprising (a) a cationic liposome, (b) an antibody or antibody fragment (TfRscFv) complexed with said cationic liposome but not chemically conjugated to said cationic liposome, and wherein said antibody or antibody fragment does not comprise a lipid tag, and (c) a therapeutic agent (e.g., a gene, plasmid DNA, or nucleic acid), for in vivo administration.
Based further on Lynch et al, it would have been obvious to utilize the ‘882 cationic immunoliposome complex for the delivery of a nucleic acid that encodes an anti-α-syn scFv intrabody for the treatment of Parkinson’s disease as discussed above. It would have been obvious to do so in order to deliver “[a]n scFv intrabody against the nonamyloid component of α-synuclein [in particular, the anti-α-syn scFv intrabody “NAC32” (Abstract)]” which “reduces intracellular aggregation and toxicity” (Title) and which “can serve as direct PD [Parkinson’s disease] molecular therapeutics” (Page 137, Column 2).
Claims 1-2, 4-5, 8-10 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 8,865,127 in view of Lynch et al (J Mol Biol 377:136-147, 2008).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘127 claims are drawn to a method of preparing an antibody- or antibody fragment-targeted cationic immunoliposome complex comprising (a) a cationic liposome, (b) an antibody or antibody fragment (TfRscFv) complexed with said cationic liposome but not chemically conjugated to said cationic liposome, and wherein said antibody or antibody fragment does not comprise a lipid tag, and (c) a therapeutic agent (e.g., a gene, plasmid DNA, or nucleic acid), for in vivo administration.
Based further on Lynch et al, it would have been obvious to utilize the ‘127 cationic immunoliposome complex for the delivery of a nucleic acid that encodes an anti-α-syn scFv intrabody for the treatment of Parkinson’s disease as discussed above. It would have been obvious to do so in order to deliver “[a]n scFv intrabody against the nonamyloid component of α-synuclein [in particular, the anti-α-syn scFv intrabody “NAC32” (Abstract)]” which “reduces intracellular aggregation and toxicity” (Title) and which “can serve as direct PD [Parkinson’s disease] molecular therapeutics” (Page 137, Column 2).
Claims 1-2, 4-5, 8-10 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 10,668,172 in view of Lynch et al (J Mol Biol 377:136-147, 2008).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘172 claims are drawn to a method of delivering BChE across the blood-brain barrier, comprising administering a cationic immunoliposome complex comprising (a) a cationic liposome, (b) an anti-transferrin receptor single chain Fv (TfRscFv) complexed with said cationic liposome but not chemically conjugated to said cationic liposome, and (c) a nucleic acid encoding BChE.
Based further on Lynch et al, it would have been obvious to utilize the ‘172 cationic immunoliposome complex for the delivery of a nucleic acid that encodes an anti-α-syn scFv intrabody for the treatment of Parkinson’s disease (as opposed to delivering a nucleic acid encoding BChE for the treatment of cacer) as discussed above. It would have been obvious to do so in order to deliver “[a]n scFv intrabody against the nonamyloid component of α-synuclein [in particular, the anti-α-syn scFv intrabody “NAC32” (Abstract)]” which “reduces intracellular aggregation and toxicity” (Title) and which “can serve as direct PD [Parkinson’s disease] molecular therapeutics” (Page 137, Column 2).
Claims 1-2, 4-5, 8-10 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 12/274,784 in view of Lynch et al (J Mol Biol 377:136-147, 2008).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘784 claims are drawn to a method of treating a cancer, the method consisting of:
(a) providing a transferrin receptor-targeted cationic liposomal complex comprising a cationic liposome; a transferrin receptor-targeting molecule (TfRscFv) that is complexed with (but not chemically conjugated to) the cationic liposome, wherein the transferrin receptor-targeting molecule does not comprise a lipid tag; and a nucleic acid encoding p53; and
(b) administering the transferrin receptor-targeting cationic liposomal complex to the patient.
Based further on Lynch et al, it would have been obvious to utilize the ‘784 cationic immunoliposome complex for the delivery of a nucleic acid that encodes an anti-α-syn scFv intrabody for the treatment of Parkinson’s disease (as opposed to delivering a nucleic acid encoding p53 for the treatment of cancer) as discussed above. It would have been obvious to do so in order to deliver “[a]n scFv intrabody against the nonamyloid component of α-synuclein [in particular, the anti-α-syn scFv intrabody “NAC32” (Abstract)]” which “reduces intracellular aggregation and toxicity” (Title) and which “can serve as direct PD [Parkinson’s disease] molecular therapeutics” (Page 137, Column 2).
Conclusion
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611