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 .
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 33 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because use claims are considered an improper definition of a process. See MPEP § 2173.05(q). Therefore, the claim cannot be evaluated for examination purposes and has not been further treated on the merits.
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.
Claim(s) 15, 16, 18, 19, 21, 22, 28, 29, 31 is/are rejected under 35 U.S.C. 102(a)(1)as being anticipated by Bethune et al (Mol. Cell Biol., 2006, of record).
Bethune et al teach polypeptides comprising a cargo polypeptide (e.g. native p23 or thioredoxin – considered a reductase enzyme or an antigen) and an “extracellular vesicle signal peptide” comprising a coatomer binding motif (comprising “FFKAKK”) that binds gamma-COP and is positioned C-terminal to the cargo. The p23 dimer comprised a motif of at least 24 amino acids See the abstract and Fig. 3A. Nucleic acids encoding the polypeptide and cells comprising the nucleic acid are taught on page 8012, first col.
Claim(s) 15, 29-31, 37 is/are rejected under 35 U.S.C. 102(a)(1)as being anticipated by Rudnicki et al (US 20170087188 A1, of record) as evidenced by Gurriaran et al (2021, cited by applicants).
Rudnicki et al teach the Wnt7a protein, nucleic acids that encode the protein, cells and viruses comprising the nucleic acid. The Wnt7a protein is considered “cargo” and inherently has the properties as taught by Gurriaran et al, that is, a coatomer binding motif. See the abstract, ¶’s [0030], [0049], [0131], [0133]. Wnt7a is taught to comprise a moiety that binds receptors in skeletal muscle cells ¶ [0410]-[0411].
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.
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 and 22 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 8 and 22 recite the broad recitation “…at least 16 amino acids in length…”, and the claims also recite “…preferably from 18 to 34 amino acids in length.”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 1, 2, 4, 5, 7, 8, 14, 36 are 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 extracellular vesicles (EVs) comprising cargo proteins bound to the external surface of the EV via the coatomer binding motif (CBM) “PVRASRNKRPTFLKIKKP”, does not reasonably provide enablement for EVs comprising any other CBM to tether the cargo to the external surface. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQQ2d 1400 (Fed. Cir. 1988) and include the following:
State of the prior art and level of predictability in the art: In spite of considerable interest in EVs, the prior art of record contains no description of such wherein a cargo protein is bound to the external surface by a coatomer binding motif. Bethune et al (Mol. Cell Biol., 2006) teach that COPI vesicles mediate transport in the internal secretory pathway, and teach a gamma-COP binding motif, but not that the vesicles are extracellular or that the CBM directs cargo to the external surface. Gurriaran-Rodriguez et al (Sci. Adv., 2024) teach that the “PVRASRNKRPTFLKIKKP” CBM motif was necessary for the claimed tethering of a cargo protein to an external surface of a COPI exosome/EV. Thus, the relevant art is silent with regard to other “CBMs” that provide the claimed function of directing or tethering a cargo protein to the external surface of a COPI vesicle. This clearly evidences that COPI EVs with external cargo proteins were at an early stage of development at the time of filing and that the skilled artisan would not know how to make such EVs without explicit guidance from the specification or significant empirical experimentation.
Amount of direction provided by the inventor and existence of working examples:
In the working examples, the specification teaches the same as Gurriaran-Rodriguez et al, that is, the “PVRASRNKRPTFLKIKKP” CBM was required to prepare the COPI EVs as claimed. The specification also discloses well-known methods for transformation of plant cells.
Although the specification suggests a one might attempt to construct other CBMs with the required COPI external binding functionality, there is no evidence that such would actually produce a structure capable of providing the claimed CBMs. Thus, in order to make the invention as claimed, the skilled artisan would have to further develop the methods of making and testing CBMs such that EVs of the required external cargo structure could be constructed.
Nature of the invention and Breadth of the claims: The claims are directed to general EVs, the properties of which have been outlined above. The claims are not limited to any cargo protein, CBM, or COPI protein for tethering of the cargo protein. Thus, the claimed EVs encompass a divergent genus comprising any CBM that might bind a COPI protein on an external surface such that any given cargo protein might be included on the EV. As the claims encompass a wide variety of EVs, it is incumbent upon the disclosure to set forth the manner and process of making EVs in a variety of species that is commensurate with the scope of protection sought.
Relative skill of those in the art and quantity of experimentation needed to make or use the invention: Although the level of skill in the art of EVs is high, the level of skill in the art of making EVs using a CBM to tether a cargo protein to a COPI protein on the external surface is low. One would not be able to make operative EVs with CBMs other than the single example disclosed given no more than the teachings available at the time of filing without undue experimentation. The prior art of record does not provide a single working example of an EV constructed as claimed. Likewise, all of the teachings in the instant application regarding additional CBMs are prophetic statements suggesting how the technology developed from the Wnt7a CBM might be further developed for other CBMs, with essentially no direction as to how to make a COPI EV without the disclosed “PVRASRNKRPTFLKIKKP” CBM. Given the broad scope of the claims, the early developmental stage and the unpredictability of the art at the time of filing, making embodiments of the claimed invention that are operative for other CBMs would clearly require undue experimentation. Therefore, the claims are properly rejected under 35 USC 112, first paragraph, as lacking enablement.
Given the above analysis of the factors which the courts have determined are critical in determining whether a claimed invention is enabled, it must be considered that undue and excessive experimentation would have to be conducted by the skilled artisan in order to practice the claimed invention.
Conclusion
No claim is allowed.
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/MICHAEL D BURKHART/ Primary Examiner, Art Unit 1638