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 .
Applicant’s election without traverse of I and collagen type I in the reply filed on 5/13/26 is acknowledged.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 8, 9, 11-16, 18-21, 23, 24, and 110-113 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require for the nucleic acid molecule encoding the exogenous extracellular matrix protein to encode a collagen type I, which is a genus that has not been adequately described in the specification.
Without further description of the structure required for the function, one would not be able to readily recognize which nucleic acids necessarily encode any collagen type I.
Instant claim 6 demonstrates that claim 1 is not directed to any specific sequence by reciting that the collagen type I can be an alpha 1 chain or pro-alpha(I) chain. Without further description of the genus, one would not be able to readily envision the genus of sequences.
The claims encompass nucleic acid molecules encoding any collagen type I, which encompasses any collagen type I homolog or allele from any species known or yet to be discovered of collagen type I, as well as DNA genomic fragments, spliced variants or fragment that retains collagen type I-like activity.
Although the specification discloses a Col1A1 EV, the specification does not describe an adequate species of Col1A1 sequences to demonstrate that applicant was in possession of the claimed genus at the time the invention was made. The species are not representative of the entire claimed genus.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Therefore, the scope of the claimed invention is broad and the skilled artisan would not be able to envisage the entire genus claimed of collagen type I sequences such that the skilled artisan would recognize that the applicant was in possession of the claimed genus at the time of filing.
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.
Claim(s) 1, 6, 8, 15, 16, 18, 110, 112, and 113 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Hansson et al. (WO 2020/227642 A1).
Hansson et al. teach: [0058] In certain embodiments, a wound healing polypeptide of a composition or method described herein is a collagen wound healing polypeptide. Nonlimiting examples of collagen wound healing polypeptides include collagen type I, collagen type III, collagen type IV, collagen type V, collagen type VI, collagen type VII, collagen type VIII, collagen type XII, collagen type XIII, collagen type XIV, collagen type XVI, collagen type XVII, collagen type XVIII, collagen type XIX, and collagen type XXVIII.
Hansson et al. teach: [0065] In certain aspects, the disclosure provides a polynucleotide (e.g., a RNA, e.g., a mRNA) comprising a nucleotide sequence (e.g., an open reading frame (ORF)) encoding a wound healing polypeptide. In some embodiments, the wound healing polypeptide of the invention is a wild type full length human collagen protein (e.g., collagen type I, collagen type III, collagen type IV, collagen type V, collagen type VI, collagen type VII, collagen type VIII, collagen type XII, collagen type XIII, collagen type XIV, collagen type XVI, collagen type XVII, collagen type XVIII, collagen type XIX, or collagen type XXVIII) (see Table 1).
Hansson et al. teach: [0090] In some embodiments, the polynucleotide of the invention comprising a nucleotide sequence (e.g., an ORF) encoding a wound healing polypeptide (e.g., the wild-type sequence, functional fragment, or variant thereof) is DNA or RNA. In some embodiments, the polynucleotide of the invention is RNA. In some embodiments, the polynucleotide of the invention is, or functions as, an mRNA. In some embodiments, the mRNA comprises a nucleotide sequence (e.g., an ORF) that encodes at least one wound healing polypeptide, and is capable of being translated to produce the encoded wound healing polypeptide in vitro, in vivo, in situ or ex vivo (instant claims 110 and 112).
Hansson et al. teach: [0407] In some embodiments, the pharmaceutical composition or formulation further comprises a delivery agent. The delivery agent of the present disclosure can include, without limitation, liposomes, lipid nanoparticles, lipidoids, polymers, lipoplexes, microvesicles, exosomes, peptides, proteins, cells transfected with polynucleotides, hyaluronidase, nanoparticle mimics, nanotubes, conjugates, and combinations thereof (instant claims 15 and 16).
Therefore, Hansson et al. teach a pharmaceutical composition comprising extracellular vesicles, more specifically microvesicles or exosomes, comprising a nucleic acid molecule encoding collagen type I (instant claims 1, 15, and 16).
Hansson et al. teach: [0208] Exemplary UTRs of the application include, but are not limited to, one or more 5'UTR and/or 3'UTR derived from the nucleic acid sequence of a collagen (e.g., collagen type I or collagen type I alpha 1 (Col1A1) (instant claims 6 and 8).
Hansson et al. teach: [0015] In certain aspects, the disclosure relates to compositions and delivery formulations comprising a polynucleotide, e.g., a ribonucleic acid (RNA), e.g., a mRNA, encoding a wound healing polypeptide and methods for: (i) promoting and/or improving wound healing in a human subject in need thereof by intradermally (e.g., using microneedles) or topically administering the same; (ii) preventing and/or reducing scar formation at a wound in a human subject in need thereof by intradermally (e.g., using microneedles) or topically administering the same.
Hansson et al. teach: intravenous, intramuscular, intradermal (e.g., using microneedles [0705](instant claim 18).
Hansson et al. teach: [0572] In one embodiment, the polynucleotides can be encapsulated into a delivery agent described herein and/or known in the art for controlled release and/or targeted delivery (instant claim 113).
Therefore, the claims are anticipated by Hannson et al.
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.
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.
Claim(s) 9, 11-14, 19-21, 23, 24, and 111 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hansson et al. (WO 2020/227642 A1), as applied to claims 1, 6, 8, 15, 16, 18, 110, 112, and 113 above, and further in view of Hao et al. (Small 2021, 17, 2102150, 1-12), Kanada et al. (Mol Cancer Ther, 18(12), 2019, 2331-2342), Akers et al. (J Neurooncol (2013) 113:1–11), Purushothaman et al. (Oncotarget, 2017, Vol. 8, (No. 43), pp: 73723-73732), and Huang et al. (BMC Genomics 2013, 14:319, 1-14).
Hansson et al. teach: [0058] In certain embodiments, a wound healing polypeptide of a composition or method described herein is a collagen wound healing polypeptide. Nonlimiting examples of collagen wound healing polypeptides include collagen type I, collagen type III, collagen type IV, collagen type V, collagen type VI, collagen type VII, collagen type VIII, collagen type XII, collagen type XIII, collagen type XIV, collagen type XVI, collagen type XVII, collagen type XVIII, collagen type XIX, and collagen type XXVIII.
Hansson et al. teach: [0065] In certain aspects, the disclosure provides a polynucleotide (e.g., a RNA, e.g., a mRNA) comprising a nucleotide sequence (e.g., an open reading frame (ORF)) encoding a wound healing polypeptide. In some embodiments, the wound healing polypeptide of the invention is a wild type full length human collagen protein (e.g., collagen type I, collagen type III, collagen type IV, collagen type V, collagen type VI, collagen type VII, collagen type VIII, collagen type XII, collagen type XIII, collagen type XIV, collagen type XVI, collagen type XVII, collagen type XVIII, collagen type XIX, or collagen type XXVIII) (see Table 1).
Hansson et al. teach: [0090] In some embodiments, the polynucleotide of the invention comprising a nucleotide sequence (e.g., an ORF) encoding a wound healing polypeptide (e.g., the wild-type sequence, functional fragment, or variant thereof) is DNA or RNA. In some embodiments, the polynucleotide of the invention is RNA. In some embodiments, the polynucleotide of the invention is, or functions as, an mRNA. In some embodiments, the mRNA comprises a nucleotide sequence (e.g., an ORF) that encodes at least one wound healing polypeptide, and is capable of being translated to produce the encoded wound healing polypeptide in vitro, in vivo, in situ or ex vivo (instant claims 110 and 112).
Hansson et al. teach: [0407] In some embodiments, the pharmaceutical composition or formulation further comprises a delivery agent. The delivery agent of the present disclosure can include, without limitation, liposomes, lipid nanoparticles, lipidoids, polymers, lipoplexes, microvesicles, exosomes, peptides, proteins, cells transfected with polynucleotides, hyaluronidase, nanoparticle mimics, nanotubes, conjugates, and combinations thereof (instant claims 15 and 16).
Therefore, Hansson et al. teach a pharmaceutical composition comprising extracellular vesicles, more specifically microvesicles or exosomes, comprising a nucleic acid molecule encoding collagen type I (instant claims 1, 15, and 16).
Hansson et al. teach: [0208] Exemplary UTRs of the application include, but are not limited to, one or more 5'UTR and/or 3'UTR derived from the nucleic acid sequence of a collagen (e.g., collagen type I or collagen type I alpha 1 (Col1A1) (instant claims 6 and 8).
Hansson et al. teach: [0015] In certain aspects, the disclosure relates to compositions and delivery formulations comprising a polynucleotide, e.g., a ribonucleic acid (RNA), e.g., a mRNA, encoding a wound healing polypeptide and methods for: (i) promoting and/or improving wound healing in a human subject in need thereof by intradermally (e.g., using microneedles) or topically administering the same; (ii) preventing and/or reducing scar formation at a wound in a human subject in need thereof by intradermally (e.g., using microneedles) or topically administering the same.
Hansson et al. teach: intradermally (e.g., using microneedles) or topically administering the same; (iii) reducing the visibility of a scar in a human subject in need thereof by intradermally (e.g., using microneedles) or topically administering the same; and/or (iv) treating epidermolysis bullosa in a human subject in need thereof by intradermally (e.g., using microneedles) or topically administering the same (instant claim 13).
Hansson et al. teach: The cell is a human fibroblast [0146](instant claim 14).
Hansson et al. teach: intravenous, intramuscular, intradermal (e.g., using microneedles [0705](instant claim 18).
Hansson et al. teach: [0572] In one embodiment, the polynucleotides can be encapsulated into a delivery agent described herein and/or known in the art for controlled release and/or targeted delivery (instant claim 113).
Hansson et al. do not teach cellular nanoporation (instant claim 12). It would have been obvious to load the exosome via nanoporation because Hao et al. teaches that this method is able to load exogenous cargo into exosomes efficiently while maintaining exosome integrity (abstract). Hao et al. teach that the presented technique holds great potential to prepare exosomes as smart vehicles that carry various cargos, such as clinical drugs, nucleic acid, proteins, etc. (page 9). Therefore, one would have been motivated to utilize nanoporation and expect the benefits taught by Hao et al.
It would have been obvious for the vesicles to comprise an average of at least one copy of the nucleic acid molecule per 450 EVs because discovering optimum ranges involves routine skill in the art and it was known in the art to deliver sequences encoding Col1A1 via extracellular vesicles, as taught by Hansson et al. The motivation would have been to generate a population of EVs having a sufficient number of nucleic acid to achieve wound healing (instant claim 9).
Hansson et al. do not teach delivery of the nucleic acid from a plasmid. (instant claims 11 and 111). When delivering DNA encoding the collagen, an embodiment of Hansson et al., it would have been obvious to deliver the DNA via microvesicles comprising a plasmid because Kanada et al. teach that microvesicles can functionally deliver plasmid DNA to cells (abstract). Therefore, one would reasonably expect for microvesicles loaded with plasmids comprising the DNA to successfully deliver the nucleic acids.
It would have been obvious for the extracellular vesicles to express higher levels of at least one marker selected from CD9, CD63, TSG101, and ARF6, which is not taught by Hansson et al., because Akers et al. teaches that CD9 and CD63 play roles in exosome formation and are the most common used identifiers of exosomes and have been targeted for selective isolation (page 3). Hansson et al. teach that TSG101 is also used as an exosome marker (page 4). Hansson et al. teach that ARF6 is a microvesicle marker (page 7). Therefore, one would have been motivated to select extracellular vesicles with higher expression levels of these markers with a reasonable expectation of being able to select the vesicle type based upon the known marker (instant claim 24).
Although Hansson et al. are silent as to the size of the vesicles, Purushothaman et al. teach that exosomes are secreted membrane vesicles 30-120 nm in diameter (page 73723)(instant claim 21) and therefore the exosomes are necessarily in the recited size range because they are exosomes. Additionally, Purushothaman et al. teach utilizing 5 x 106 exosomes per mL (Figure 3). Selection of this quantity was known in the art and is a matter of design choice (instant claim 19).
With regards to instant claim 20, it would have been obvious for the plurality of extracellular vesicles to comprise at least 10 ng of the nucleic acid as a matter of design choice. This parameter is dependent upon the specific quantity of vesicles, which is not required by the claim; and is considered to be within the normal range of 5 x 106 exosomes per mL as taught by Purushothaman et al. One would have been motivated to deliver at least 10 ng of the nucleic acid to result in expression of the product. Additionally, Huang et al. is evidence that even a single exosome can carry 10-15 ng of RNA (page 2).
With regards to instant claim 23, the nucleic acid being present at a level of at least 2-fold higher than a level of naturally occurring exosomes is considered obvious because the intended use of the vesicle is to load and deliver Col1A1. Therefore, it would have been obvious for the amount to at least be 2-fold of what naturally occurs as a matter of design choice with the expectation of Col1A1 delivery at an amount acceptable for wound healing.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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