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 .
Status of Claims
Claims 1-2, 4-7, 13-16, 123-124, 129, 132, 157, 163, 171, 248, 270, and 273 are pending.
Priority
Claims 1-2, 4-7, 13-16, 123-124, 129, 132, 157, 163, 171, 248, 270, and 273 are a 371 of PCT/US 2022/081870 filed on December 16, 2022, which has priority to PRO 63/408,821 filed on September 21, 2022, and to PRO 63/291,323 filed on December 17, 2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on March 14, 2025, was filed before the mailing of the First Office Action on August 1, 2026. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Claim Objections
The following claims are objected to because of the following informalities:
Claim 4 recites “wherein the lipid particle is a pseudotyped lentiviral particle” and should read as “wherein the lipid particle is a pseudotyped lentiviral particle.”
Claim 6 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claims. Accordingly the claim has not been further treated on the merits.
Examiner’s Note
For purposes of compact prosecution, the examiner notes that claims 6 and 7 would have been rejected under Broder for teaching that the F glycolprotein is initially synthesized as a precursor F0 which is cleaved into the disulfide-linked F1 and F2 subunits by cathepsin L within the host cell [Background ¶ 4].
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Applicant is advised that should claim 13 be found allowable, claim 14 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 14 states “at or about 23 amino acid residues” referencing deletion in the NiV-F cytoplasmic tail. However, this limitation is already included in claim 13 where the cytoplasmic tail has a deletion of 23 to 27 contiguous amino acid residues given the cytoplasmic tail is only 28 residues in length. Thus despite the difference in wording, the claims have substantially the same scope.
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 5, 6, and 273 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.
Claim 5 recites “the lipid particle or pseudotyped lentiviral particle of any of claims 1-4”. However, claim 3 has been canceled. As such, claim 5 improperly depends from a canceled claim rendering the scope of claim 5 unclear.
Claim 6 recites “the lipid particle or pseudotyped lentiviral particle of any of claims 1-5”. Although improper for being a multi-dependent claim that depends from another multi-dependent claim. Again, claim 3 has been canceled. As such, claim 6 also improperly depends from a canceled claim.
Regarding claim 273, the phrase "e.g." coupled with parentheses renders the claim indefinite because it is unclear whether the limitations within the parentheses are a part of the claimed invention. See MPEP § 2173.05(d).
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 1-2, 4-5, 13-16, 123-124, 129, 132, 157, 163, 171, 248, 270, and 273 are rejected under 35 U.S.C. §103 as being unpatentable over Palomares et al. [Nipah virus envelope-pseudotyped lentivirus efficiently target ephrin B2-positive stem cell populations in vitro and bypass the liver sink when administered in vivo, Journal of Virology, 2013], in view of Khetawat and Broder (Hereinafter Broder) [A functional henipavirus envelope glycoprotein pseudotyped lentivirus assay system, BMC Virology Journal, 2010], in view of Lentiviral Production [https://www.respiratorygenetherapy.org.uk/copy-of-nonviral-vector-development, web.archive.org, May 2021], in view of UniProt [H6V874 – H6V874_NIPAV, 2012], in view of Benhur et al. [US 2015 050242 A1], in view of Urak et al. [Conditionally replicating vectors mobilize chimeric antigen receptors, Mol Ther Methods Clin Dev., 2020].
Regarding claim 1, Broder teaches a pseudotyped lentiviral particle comprising paramyxovirus envelope glycoproteins that include Nipah virus F and G glycoproteins [Abstract Background]. Broder further teaches a Henipavirus assay envelope glycoprotein-pseudo-typed lentiviral vectors that incorporate NiV-F and NiV-G glycoproteins into lentiviral particles [Specificity of henipavirus envelope glycoprotein pseudo-typed lentivirus particles ¶ 1], and because lentiviral particles are enveloped particles comprising a lipid bilayer derived from the producer cell membrane, the disclosed pseudo-typed lentiviral particles comprise a lipid bilayer. Additionally, NiV is a member of paramyxovirinae family, and therefore NiV-G constitutes a paramyxovirus glycoprotein as recited in claim 1. Furthermore, Border teaches variant NiV-F glycoproteins comprising modified cytoplasmic tails. Figure 4 specifically discloses the wild-type NiV-F cytoplasmic tail sequence which corresponds to Applicant’s SEQ ID NO: 4. Border further describes generating and evaluating multiple NiV-F cytoplasmic tail truncation variants that include having deletions of contiguous amino acid residues at or near the C-terminus of the cytoplasmic tail [Fig. 4B]. Figure 4B illustrates truncated NiV-F amino acid residues that have deletions within of approximately 23 deletions to 28 contiguous deletions [Id]. Additionally, Palomares et al. teaches Nipah virus envelope-pseudotyped lentiviruses comprising NiV-F and G glycoproteins that are incorporated into lentiviral particles. Palomares et al. also teaches that truncation of the NiV-F cytoplasmic tail improves production and/or titers of pseudotyped particles [Introduction ¶ 6]. Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Border where a pseudotyped lentivirus incorporates a NiV-F cytoplasmic tail truncation within a known range, including the deletions of 23-27 contiguous amino acid residues with the further teachings of Palomares et al. that further teaches that truncation of the cytoplasmic tail for NiV-F improves production and/or titers of pseudotyped particles. Because of this, there is a reasonable expectation of success that a person of ordinary skill in the art would have recognized the teachings of both Border and Palmores et al. where an artisan could engineer a lipid particle that included a lipid bilayer, a paramyxovirus glycoprotein and truncated cytoplasmic tail derived from the wild-type NiV-F glycoprotein where these components are incorporated into a pseudotyped lentivirus.
For claim 2 where the lipid bilayer is derived from a membrane host cell used for producing a retroviral vector, Lentiviral Production teaches that the viral virions fuse with the cell surface membrane of the production cell and bud off into the mammalian cell culture medium where the active lentiviral vector particles are surrounded by a lipid bilayer which contains the envelope proteins [Budding of the Virion]. Additionally, Palomares et al. also discloses culturing lentivirus vectors in 293T cells, i.e. mammalian cells [Virus Production ¶ 1].
For claim 4 where the lipid particle of claim 1 is a pseudotyped lentiviral particle, Border and Palomares disclose pseudotyped lentiviral particles [Results ¶ 3, Virus Production ¶ 1, respectively].
For claim 5 where the pseudotyped lentiviral particle with the variant NiV-F protein exhibit fusogenic activity, Palomares et al. teaches that a hypoglycosylated hyperfusogenic NiV-F mutant demonstrated increased infectivity in vitro [Hypoglycosylated hyperfusogenic NiV-F mutant demonstrated increased infectivity in vitro ¶ 1].
For claims 13 and 14 where the modified cytoplasmic tail is a truncated NiV-F cytoplasmic tail that has a deletion of from 23 to 27 contiguous amino acids at or near the C-terminus of the wild-type Nipah virus F protein cytoplasmic tail set forth in SEQ ID NO: 4, see the analysis for claim 1 that discusses Figure 4B in Broder.
For claim 15 where the modified cytoplasmic tail is a truncated NiV-F cytoplasmic tail set forth in SEQ ID NO: 27, Although Broder does not disclose the precise amino acid sequence of Applicant’s SEQ ID NO: 27, Broder does disclose a NiV-F cytoplasmic tail sequence corresponding to Applicant’s SEQ ID NO: 27. The only difference is the terminal residue where Broder discloses EKKR and Applicant discloses EKKRN. However, Broder further discloses multiple NiV-F cytoplasmic tail truncation variants generated by varying the number of C-terminal amino acid deletions [Figure 4]. Given this, it would have been prima facie obvious to a person of ordinary skill prior to the filing of the claimed invention to modify the systems and methods of Broder where it was disclosed the NiV-F cytoplasmic tail could function under multiple variant deletion types of the cytoplasmic tail. Additionally, Palomares et al. also disclosed the benefit of a truncated cytoplasmic tail as it relates to NiV-F as discussed in claim 1. There would have been a reasonable expectation of success for a person of ordinary skill in the art to recognize the teachings of both Broder and Palomares et al. where both disclosed the importance of truncating the NiV-F cytoplasmic tail where Broder taught contiguous deletions up to 28 and would have necessarily included the specific amino acid claimed by Applicant.
For claim 16 where the NiV-F variant comprises the sequence set forth in SEQ ID NO: 306 at various identity percentages, UniProt discloses the wild-type Nipah virus F glycoprotein was known in the art and discloses that the wild-type amino acid sequence is about 540 amino acids in length [Sequence]. Applicant’s SEQ ID NO: 306 corresponds to the known NiV-F sequence but is truncated relative to the wild-type protein by removal of an N-terminal region and the 23 amino acid sequence deletion on the cytoplasmic tail. Given this and the teachings by Broder discussion about various deletions of the NiV-F cytoplasmic tail, UniProt teaches the exact sequence as claimed by Applicant in claim 16.
For claim 123 where the G protein is a biologically active portion of wild-type NiV-G that is truncated in which the G protein lacks up to 34 contiguous amino acids as set forth in SEQ ID NO: 305, Benhur et al. discloses Nipay virus envelope pseudotyped lentiviruses with a wild-type, biologically active, and truncated NiV-G protein can have deletions of 5, 10, 15, 20, 25, and 30 amino acids at or near the N-terminus of the NiV-G peptide [¶ 0039]. Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Benhur et al. where the authors engineered a truncated NiV-G peptide at the at or near the N-terminal that was incorporated into a pseudotyped lentivirus. Therefore, a person of ordinary skill would have a reasonable expectation of success using the teachings of Benhur et al. coupled with Broder that a pseudotyped lentivirus that incorporated a truncated cytoplasmic tail associated with NiV-F and a truncated N-terminal region associated with NiV-G.
For claim 124 where the G protein is a NiV-G functionally active variant that exhibits reduced binding to Ephrin B2 or Ephrin B3, Benhur et al. teaches that mutations in NiV-G that completely abrogate ephrinB2 and B3 binding are known but do not impact the association of NiV-G with NiV-F [¶ 0043]. Additionally, this would allow for specific targeting of other desired cell types that are not ephrinB2 positive [Id].
For claim 129 where the lipid particle G protein is linked to a binding domain that binds to a target cell surface molecule on the target cell, Benhur et al. teaches that both the NiV-G and NiV-F are capable of increasing infectivity of the NiVpp lentivirus [¶ 0015].
For claim 132 where the target cell is selected from a group consisting of a Markush listing that includes CNS cells, Benhur et al. discloses that target cells can include central nervous system cells [¶ 0016]. While Palomares et al. disclosed cancer cells, hematopoietic stem cells, liver cells, and T cells [Introduction ¶ 2, Figure 4, Cells and Culture Conditions].
For claim 157 where the claimed invention further comprises an exogenous agent for delivery to a target cell, Broder teaches the use of an exogenous agent that includes a green fluorescent protein [Abstract Background]. This falls under what Applicant considers an exogenous agent as described in Paragraph [0054] of Applicant’s specification where it states “In some of any of the provided embodiments, the exogenous agent is or encodes a therapeutic agent or a diagnostic agent”.
For claim 163 where the exogenous agent encodes a chimeric antigen receptor, Urak et al. teaches that lentiviral vectors can be used for mobilizing chimeric antigen receptor delivery [A crLV-derived CAR vector does not impact lentiviral production and transduction ¶ 1].
For claim 171 where a polynucleotide includes the modifications found in claim 1, see analysis for claim 1.
For claim 248 where a method for making the lipid particle, Palomares et al. discloses a method for providing a cell that contains the polynucleotide of claim 171 where the cells are cultured under conditions allowing for production of a lipid particle, and further separating and/or purifying the lipid particles from the cells [Cells and Culture Conditions]. Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the teachings of Palomares et al. to include the method of producing the lipid particle, e.g. pseudotyped lentivirus with the modifications of claim 171 given that both Palomares et al. and Broder both discuss methods in making and/or constructing a lipid particle, e.g. lentiviral vector, with a modified NiV-F portion. Given this and the fact that vector production is a well-known science, a person of ordinary skill in the art would have a reasonable expectation of success to combine the teachings of both Broder and Palomares et al. in order to develop a polynucleotide that could be produced in known strains of mammalian cells as described by Palomares et al. in the author’s cells and culture conditions section of the article.
For claim 270, Benhur et al. discloses that administration can be through known systemic means [¶ 0042].
For claim 273, Benhur et al. further discloses that administration of the Nipah virus envelope pseudotyped lentiviruses carrying an exogenous agent could be used in the treatment of Huntington’s disease [¶ 0016].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Broder and Palomares et al. where both disclosed methods for modifying lipid particles to include modified NiV-F cytoplasmic tail with the further teachings of Benhur et al. where the authors disclosed a method of also included a truncated NiV-G protein where the deletions were located at or about the N-terminal portion given that all three references disclose the increased titration when truncated NiV-F cytoplasmic tail is present, as well as the NiV-G truncation portion. Based on this, a person of ordinary skill in the art would have had a reasonable expectation of success to construct a lipid particle based on the teachings of Broder and Palomares et al. combined with the teachings of Benhur et al. with the further teachings by Palomares et al. that discloses known methods in producing lentiviral vectors using mammalian cells with the additional teachings of Benhur et al. that teaches these engineered lipid particles are capable of being administered to a subject for purposes of treating diseases and/or disorders.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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