DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 80-89), drawn to a nanoparticle, in the reply filed on 09/08/2025 is acknowledged. Additionally, applicants were required to elect the two or more genes present in the claimed DNA molecule. Applicants have elected the species wherein the DNA molecule contains a first gene encoding a CAR. Applicants have modified the scope of the claim to leave the second gene as generic. This election is considered acceptable and examination will proceed. Claims 80-85 and 88-89 read on the elected species. Claims 86-87 and 90-99 are withdrawn from consideration, as being directed to a non-elected invention. Claims 80-85 and 88-89 have been examined on the merits.
Priority
Acknowledgement is made of Applicants’ claim for benefit of US Provisional application 63/188,782 (filed 05/14/2021).
Drawings
The drawings are objected to because there are color images with no granted petition to accept color images.
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).
Claim Objections
Claims 81 objected to because of the following informalities:
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 81 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 81: The meaning of an “MLS sequence” in claim 81 is unclear. The instant application does not provide the full term for the abbreviation “MLS”. Additionally the specification does not provide a definition for the abbreviation “MLS”. A Google search for the term “MLS sequence” teaches the term can refer to “maximum length sequence”, “mitochondrial leader sequence”, “multi-locus sequence”, “macrolide-lincosamide-streptogram B resistance sequence”, “Musladin-Lueke Syndrome”, “mitochondrial localization signal”, and various other art related terms. The term “MLS” is therefore not immediately clear based on the state of the art.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 80, 82, 84, 85, 88, and 89 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smith et al (Nature Nanotechnology, 2017).
Smith et al discloses a nanoparticle comprising positively charged poly-ß-amino ester (PBAE) based polymer bound to a peptide comprising microtubule associated sequences (MTAS) and nuclear localization signals (NLS) (See Sec. Designing nanocarriers to achieve CAR expression in T cells and Fig. 1). The nanoparticle is loaded with plasmids encoding a CAR comprising a CD19-specific scFV, a CD8 transmembrane domain, a 4-1BB transduction domain and a CD3 ζ cytoplasmic domain and a reporter gene and plasmids encoding an iPB7 transposase (See Sec. Plasmid construction (1) and Fig. 1). The plasmids are negatively charged (See Fig. 1). The outer portion of the nano particle comprises polyglutamic acid (PGA) fused to anti-CD3e f(ab’)2 antibodies (See Fig. 1). The nanoparticle of Smith et al is lyophilized (See Sec. Nanoparticle preparation and Fig. 1). Smith et al further discloses clinical testing of nanoparticle-mediated CAR T cell programming will likely require that nanoparticle-delivered genetic materials be in the form of minicircles to exclude the possibility of unintentionally integrating antibiotic resistance genes into the host genome (See Sec. Conclusion, 2nd to last paragraph).
Regarding claim 80: Smith et al discloses a nanoparticle comprising an interior portion comprising plasmids encoding a CAR and a transposon (reads on one or more DNA molecules) and a PBAE polymer bound to a peptide (reads on polymer bound to a protein). The peptide of smith comprises a NLS and a MTAS sequence which reads on the protein comprises a first amino acid sequence directing the protein to the nucleus of the cell and a second sequence. The polymer of Smith et al is positively charged and the plasmids are negatively charged which reads on the one or more DNA molecules are associated with the polymer by way of opposing charges.
Regarding claim 82: Following the discussion of claim 1 above, Smith et al discloses the polymer is poly-ß-amino ester.
Regarding claim 84: Following the discussion of claim 80 above, Smith et al discloses the nanoparticle comprises a plasmid which encodes a CAR gene and a reporter gene and a plasmid which encodes a transposon which reads on the DNA molecules comprise two or more genes wherein a first gene is a CAR gene.
Regarding claim 85: Following the discussion of claims 84 and 80 above, the CAR of Smith comprises a CD19-specific scFV (reads on targeting ligand consisting of a variable heavy chain and a variable light chain of a Fab fragment), a CD8 transmembrane domain, and a CD3ζ cytoplasmic domain.
Regarding claim 88: Following the discussion of claim 80 above, the exterior of the nanoparticle of Smith et al comprises polyglutamic acid fused to anti-CD3e f(ab’)2 antibodies which reads on the exterior is a polyglutamic acid and a targeting group which is a Fab2 fragment.
Regarding claim 89: Following the discussion of claim 80 above, Smith et al discloses the nanoparticle is lyophilized.
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.
Claims 80, 82-85, 88, and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al (Nature Nanotechnology, 2017).
The teachings of Smith et al are set forth above.
Smith et al anticipates claims 80, 82, 84, 85, 88, and 89.
Regarding claim 83: Following the discussion of claim 80 above, Smith et al discloses a nanoparticle comprising a plasmid (reads on DNA molecule). Smith et al further discloses clinical testing of nanoparticle-mediated CAR T cell programming will likely require that nanoparticle-delivered genetic materials be in the form of minicircles to exclude the possibility of unintentionally integrating antibiotic resistance genes into the host genome.
Smith et al does not disclose a nanoparticle comprising a minicircle plasmid.
Given that Smith et al discloses a nanoparticle comprising plasmid DNA and Smith et al further discloses clinical testing of nano-particle mediated CAR T cell programming will likely require the use of minicircles to prevent integration of antibiotic resistance genes into the host genome, it would have been prima facie obvious to modify the nanoparticle of Smith et al to use minicircle plasmids rather than conventional plasmids in order to use the nanoparticle for clinical testing. One would have been motivated to modify the nanoparticle of Smith et al because Smith et al discloses using minicircles prevents integration of antibiotic resistance genes into the host genome. There is a reasonable expectation of success because Smith et al teaches minicircle plasmids can be used to deliver genetic materials.
Claims 80-85, 88, and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al (Nature, Nanotechnology, 2017) in view of Brooks et al (Advanced Drug Delivery Reviews, 2005).
The teachings of Smith et al are set forth above.
Smith et al anticipates claims 80, 82, 84, 85, 88, and 89 and renders claim 83 obvious.
Regarding claim 81: Following the discussion of claim 80 above, Smith et al discloses a nanoparticle comprising a polymer bound to a protein comprising an NLS.
Smith et al does not disclose the protein further comprises a TAT or MLS sequence.
Brooks et al teaches a Tat peptide can be used for intracellular delivery of particles, peptides, proteins, and nucleic acids (See abstract).
Given that Smith et al discloses a nanoparticle for programming T cells and Brooks discloses a Tat peptide can be used to deliver particles into cells, it would have been prima facie obvious to modify the polymer bound protein of Smith et al to further comprise a Tat peptide. One would have been motivated to add a Tat peptide to the protein of Smith et al because Brooks e al teaches a Tat peptide improves intracellular delivery of proteins and particles. There is a reasonable expectation of success because using a Tat peptide for intracellular delivery is a known technique in the field.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633