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 .
DETAILED ACTION
Request for Continued Examination Under 37 CFR 1.1143
A request for continued examination (RCE) under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission mailed on March 27, 2025 has been entered.
Claims 30-33 have been canceled. New claim 35 is acknowledged. Claim 28 has been amended.
Claims 16, 26-29 and 35 are pending in the instant application.
Accordingly, claims 16, 26-29 and 35 have been examined on the merits as detailed below:
Response to Arguments
Applicant's Amendment and Response filed March 27, 2025 has been considered. Rejections and/or objections not reiterated from the previous Office Action mailed December 27, 2024 are hereby withdrawn. Any arguments addressing said rejections and/or objections are moot. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
After careful reconsideration of the pending claims, a new grounds of rejection is made of record as presented below:
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 16, 26-29 and 35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), because the specification, while being enabling for a method of delivering a nucleotide encoding a gene to a patient suffering from a lung disease due to a mutation in at least one gene expressed in the lung, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition targeting lung tissue, comprising at least the nucleotide encoding the gene which does not contain the mutation, wherein the nucleotide encoding the gene is incorporated into lentiviral or lentiviral-like particles pseudotyped with syncytin protein and the pharmaceutical composition selectively transduces the lung compared with the liver, wherein the nucleotide encoding the gene is packaged into a lentiviral vector particle pseudotyped with a syncytin protein selected from murine Syncytin A and human Syncytin-2, does not reasonably provide enablement for a method of delivering a nucleotide encoding a gene to a patient suffering from a lung disease due to a mutation in at least one gene expressed in the lung, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition targeting lung tissue, comprising at least the nucleotide encoding the gene which does not contain the mutation, wherein the nucleotide encoding the gene is incorporated into lentiviral or lentiviral-like particles pseudotyped with syncytin protein and the pharmaceutical composition selectively transduces the lung compared with the liver, wherein the nucleotide encoding the gene is packaged into a lentiviral vector particle pseudotyped with a syncytin protein selected from human Syncytin-1. 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 and/or use the invention commensurate in scope with these claims. This is a scope enablement rejection.
There are many factors to be considered when determining whether there is sufficient evidence to support determination that a disclosure does not satisfy the enablement requirements and whether any necessary experimentation is undue. These factors have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include:
(1) the quantity of experimentation necessary,
(2) the amount of direction or guidance presented,
(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 or unpredictability of the art, and
(8) the breadth of the claims.”
The nature of the invention and the breadth of the claims:
The claims are drawn to a method of delivering a nucleotide encoding a gene to a patient suffering from a lung disease due to a mutation in at least one gene expressed in the lung, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition targeting lung tissue, comprising at least the nucleotide encoding the gene which does not contain the mutation, wherein the nucleotide encoding the gene is incorporated into lentiviral or lentiviral-like particles pseudotyped with syncytin protein and the pharmaceutical composition selectively transduces the lung compared with the liver, wherein the nucleotide encoding the gene is packaged into a lentiviral vector particle pseudotyped with a syncytin protein selected from human Syncytin-1 and human Syncytin-2.
The amount of direction or guidance and presence/absence of working examples:
The Specification teaches:
There is a need for providing composition comprising at least a drug for use in the prevention and/or treatment of the lung diseases, which targets lung tissue and which has no liver toxicity (i.e. which does not target the liver);
FIG. 1 shows the bioluminescence analysis in representative mice at week 2. A clear signal is observed in spleen and in the lungs following murine syncytin A LV (lentiviral vector) delivery. Contrary to VSVG, syncytin A does not transduce liver; and
Overall, by measuring transduction and transgene expression in lung, spleen and liver, it is clear that murine Syncytin-A-LV has a unique transduction profile. Based on qPCR, Syncytin A-LV can transduce the lung and spleen very efficiently but not the liver.
The § 1.132 Declaration of inventor Anne Galy filed September 25, 2023 teaches additional experimental results in Table 1 associated with the Declaration show that none of the conditions tested with the LV-Human SYN2-GFP resulted in the transduction of human hepatocyte cell lines. The Declaration concludes that human syncytin 2-pseudotyped vectors do not transduce human hepatocytes at any detectable levels. It should be noted that FIG. 9 of the present Specification shows that human syncytin 2 can be used to pseudotype lentiviral vectors to efficiently transduce human primary pulmonary epithelial cells.
The Specification and the § 1.132 Declaration provide working examples wherein a method of delivering a nucleotide encoding a gene to a patient suffering from a lung disease due to a mutation in at least one gene expressed in the lung, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition targeting lung tissue, comprising at least the nucleotide encoding the gene which does not contain the mutation, wherein the nucleotide encoding the gene is incorporated into lentiviral or lentiviral-like particles pseudotyped with syncytin protein and the pharmaceutical composition selectively transduces the lung compared with the liver, wherein the nucleotide encoding the gene is packaged into a lentiviral vector particle pseudotyped with a syncytin protein selected from murine Syncytin A and human Syncytin-2. However, such a disclosure would not be considered enabling for wherein the nucleotide encoding the gene is packaged into a lentiviral vector particle pseudotyped with a syncytin protein selected from human Syncytin-1. The Wands factors are being considered and the analysis of enablement favors undue experimentation. See MPEP § 2164.01.
The state of the prior art and the predictability or unpredictability of the art:
The claimed invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). The following is cited and discussed herein to illustrate the state of the art of CRISPR technology in neurodegenerative diseases treatment.
The following is cited herein to illustrate the unpredictability of using the syncytin protein to exert a unique transduction profile in cells: For example, the unpredictability in devising the method as claimed is evidenced in Applicant’s Disclosure which teaches:
Surprisingly, and contrary to what would be expected from the prior art, the authors have found that syncytin may be used to pseudotype LV and as such may be used for targeting gene delivery in lung tissue without risk of liver toxicity.
The present Specification and the § 1.132 Declaration provide working examples wherein murine syncytin A and human syncytin 2 are used to pseudotype lentiviral vectors to efficiently transduce lung tissue, but not the liver. While human syncytin 2 is related to human syncytin 1, they are entirely different proteins. It should be noted that different “modifications” in a protein sequence can have drastically contrasting effects on its structure and thus its stability and function. See, for example, WHISSTOCK et al. (Biophysics, 2003 Vol. 36:307-340). Therefore, results reported for human syncytin 2 ability to exert a unique transduction profile in lung cells versus liver cells would not predictably correlate and translate to results for human syncytin 1.
Google AI Overview downloaded from is human syncytin 1 related to human syncytin 2 - Google Search on November 4, 2025 disclose:
Human syncytin 1 and syncytin 2 are related; both are fusogenic proteins encoded by human endogenous retroviruses (HERVs) that play a key role in placental development, but they are derived from different HERV families and have distinct expression patterns and specific functions. Syncytin 1 comes from the HERV-W family, while syncytin 2 comes from the HERV-FRD family.
The level of skill in the art:
The relative skill of those in the art is considered to be high, being a graduate student or post-doctoral fellow in a biological science.
The quantity of experimentation necessary:
A review of the instant application finds results wherein murine syncytin A and human syncytin 2 are used to pseudotype lentiviral vectors to efficiently transduce lung tissue, but not the liver. The present Specification does not show that human syncytin 1 is used to pseudotype a lentiviral vector to efficiently transduce lung tissue, but not the liver. In other words, the unique transduction profile in cells is demonstrated with murine syncytin A and human syncytin 2, but not human syncytin 1.
Applicants do not exemplify using the human syncytin 1 protein in the method as claimed. As the present Specification indicates, it is surprising, and contrary to what would be expected from the prior art, that murine syncytin A and human syncytin 2 may be used to pseudotype LV and as such may be used for targeting gene delivery in lung tissue without risk of liver toxicity. Accordingly, one of skill would not find the examples of using murine syncytin A and human syncytin 2 to pseudotype lentiviral vectors to efficiently transduce lung tissue, but not the liver enough to overcome the uncertainty and unpredictability in using the human syncytin 1 protein.
In order to practice the invention using the Specification as outlined above, the quantity of experimentation required to practice the invention as claimed would require the de novo determination of how to overcome the unpredictability of using syncytin protein to pseudotype LV and as such may be used for targeting gene delivery in lung tissue without risk of liver toxicity. As supported by Google AI Overview, Whisstock et al. and Applicant’s own Disclosure, such analysis is replete with trial and error experimentation. Such experimentation represents an inventive and unpredictable undertaking in itself, with each of the many intervening steps, not providing any guarantee of success. Given the art recognized unpredictability discussed above, this determination would not be routine and would require undue trial and error experimentation.
Due to the scope of the claims, one of skill in the art would be required to further undertake extensive trial and error experimentation with a large number of subjects and controls, to use syncytin protein to pseudotype LV and as such may be used for targeting gene delivery in lung tissue without risk of liver toxicity. Since the specification fails to provide any real guidance for the methods as claimed for using the human syncytin 1 protein, and since resolution of the various complications in regards to tissue targeting and cell transduction profile is unpredictable, one of skill in the art would have been unable to practice the invention, without engaging in undue trial and error experimentation.
Thus, in view of the breadth of the claims, the lack of guidance, and the lack of working examples, the instant specification is not found to be enabling for using human syncytin 1 protein to pseudotype a lentiviral vector to efficiently transduce lung tissue, but not liver. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention. Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled over the full scope claimed.
In view of the foregoing, one of ordinary skill in the art would not be able to make and use the claimed invention over the scope claimed. The Wands factors have been weighed and favor undue experimentation.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635