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 . 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.
Claim Rejections - 35 USC § 112 –
Scope of Enablement and Prevention
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 26-29 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 treating breast cancer [Example 8], does not reasonably provide enablement for “preventing Alzheimer's disease, autoimmune conditions, cancer, cardiovascular disease, cystic fibrosis, Duchenne muscular dystrophy, hemophilia, Huntington's disease, lysosomal storage disease, liver disorders, macular degeneration, myotonic dystrophy, neuromuscular disease, Parkinson's disease, sepsis, spinal muscular atrophy, stroke, genetic disorders, CNS conditions, neuro-degenerative disorders, heart disorders, Phenylketonuria, heart failure or ALS”, generally. 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 the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).[1]
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative
skill level
The invention relates to a method of administering a composition comprising an extracellular vesicle comprising a single pass EV transmembrane protein fused to a moiety on the surface of the EV and/or cargo, in the treatment of diseases or conditions. The relative skill of those in the art is high, that of an MD or PHD. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites Marsh et al (BMJ, 2000, 321, 1-2).
Marsh taught that, while Parkinson’s disease is the only neurodegenerative disorder with a range of medical and neurosurgical treatments that substantially reduce clinical symptoms, there is no cure [1st paragraph].
The breadth of the claims
Since the instant specification provides no limiting definition of the term “prevention”, the term will be interpreted expansively. The term “prevention” may vary widely in meaning, from “preventing” a disease from occurring to “preventing” it from progressing. Nor is the term limited by any time frame.
The claims are thus very broad insofar as they suggest that one will not experience the disease when taking the claimed agent; that should one get the disease, it will not worsen; or that following its treatment, it will not recur. While such “prevention” might theoretically be possible under strictly controlled laboratory conditions, as a practical matter it is nearly impossible to achieve in the “real world” in which patients live.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction or guidance for practicing the claimed invention in its “full scope”. No reasonably specific guidance is provided concerning useful protocols for carrying out the invention as claimed, other than treating breast cancer. The latter is corroborated by the working examples.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed agents could be predictably used as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the claimed invention in its “full scope” a person of ordinary skill in the art would have to engage in undue experimentation, with no reasonable expectation of success.
The Applicant is encouraged to remove the word “preventing” from the claim language, especially at claim 26(c).
Claim Rejections - 35 USC § 112 –
Indefiniteness, Indefinite Language, Lack of Antecedent Basis
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 6 and 12-13 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.
Regarding claim 6, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding lack of antecedent basis, claims 12-13 recite the limitation "the molecule" in lines one and two, respectively. There is insufficient antecedent basis for this limitation in the claims.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-2, 5-15, 25-28 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Dar et al (WO 2021/084274 A1).
Dar taught an extracellular vesicle (EV), further comprising a phosphatidylserine (PS)-binding protein and/or peptide bound to the outer surface of the EV [claim 1]. An EV-binding protein was bound to the PS-binding protein, and the EV-binding protein was LAMP-2B (e.g., a single pass EV transmembrane protein) [page 22, line 24]. Additionally, Dar taught cargo on the surface of the EV, interacting with a moiety on the outer surface of a cell [page 31, lines 20-28], wherein a cargo-binding protein was a RNA- and/or DNA-binding protein [page 28, lines 25-29].
Claim 1 is rendered prima facie obvious over the teachings of Dar, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., EV, single pass EV transmembrane protein, cargo) were known in the prior art (e.g., Dar) and one skilled in the art could have combined the elements as claimed, by known methods with no change in their respective functions, and the combination would yield nothing more than predictable results (e.g., an EV) to one of ordinary skill in the art. MPEP 2143.A.
Dar reads on claims 1, 6-7 and 25.
Claim 2 is rendered prima facie obvious because Dar taught the composition substantially devoid of vesicle aggregates [claim 5].
Claim 5 is rendered prima facie obvious because Dar taught the phosphatidylserine-binding protein and/or peptide comprised a polypeptide sequence having at least 80%, at least 90%, at least 95% or at least 100% sequence identity to SEQ ID NO: 1 [claim 7].
Claim 8 is rendered prima facie obvious because Dar taught cargo as a protein or peptide [claim 13].
Claims 9-10 are rendered prima facie obvious because Dar taught an organic compound-based or polypeptide-based release system [page 31, lines 29-30], activated to release cargo from the EV [page 31, lines 21-22].
Claims 11-13 are rendered prima facie obvious because Dar taught that the composition was co-administered with, and/or further comprised, a molecule that enhanced release of the EV from endosomes; wherein the molecule that enhanced release of the EV from endosomes was a molecule that bound to protons; wherein the molecule that enhanced release of the EV from endosomes was chloroquine [claims 16-18].
Claim 14 is rendered prima facie obvious because Dar taught exosomes [claim 20].
Claim 15 is rendered prima facie obvious because Dar taught derivation from mesenchymal stem cells [page 19, line 15].
Claim 26 is rendered prima facie obvious because Dar taught using the composition for purifying an EV [claim 32].
Claim 27 is rendered prima facie obvious because Dar taught gene editing [page 30, line 19].
Claim 28 is rendered prima facie obvious because Dar taught immobilized to a solid support [claim 34].
Claim 30 is rendered prima facie obvious because Dar taught exogenous binding of GAPDH to the EV surface [page 3, lines 8-11].
Claim 31 is rendered prima facie obvious because Dar taught that the EV was targeted to particular cell types or tissues, by expressing on their surface a targeting moiety such as a peptide. Suitable peptides were those which bound to cell surface moieties such as receptors, or their ligands found on the cell surface of the cell to be targeted [page 33, lines 25-33].
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Dar et al (WO 2021/084274 A1), in view of Pavlakis et al (WO 2017/173367 A2).
The 35 U.S.C. 103 rejection over Dar was previously described.
Additionally, Dar taught that media was used for culturing and seeding of source cells; cells were further incubated, collection of the media from the cells for isolation of extracellular vesicles [Example 1].
Dar did not teach a bioreactor, as recited in claim 29.
Pavlakis taught that culturing cells in a hollow fiber bioreactor yields more EVs as compared to culturing the cells in conventional flasks [0050, 0106-0107].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Dar, a bioreactor, as taught by Pavlakis. The ordinarily skilled artisan would have been motivated to increase the yield of the EVs, as taught by Pavlakis [0050, 0106-0107].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELESTE A RONEY whose telephone number is (571)272-5192. The examiner can normally be reached Monday-Friday; 8 AM-6 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CELESTE A RONEY/Primary Examiner, Art Unit 1612
[1] As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.
Prosecution Insights