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 .
Priority
No priority has been filed in the application and therefore, all claims are given the effective filing date of 01/18/2024.
Application Status
Claim 1 is currently pending.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “A method for recuing”. It is interpreted that “recuing” is supposed to recite “rescuing” and will be treated as such.
Appropriate correction is required.
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.
Claim 1 is 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 a method for rescuing ABCA3 deficiency caused by a splicing mutation of ABCA3 within a Sftpc-Cre;Abca3flox/flox mouse model, comprising using CRISPR/Cas9 to delete a loxP site located at an intronic region of ABCA3 flox, does not reasonably provide enablement for a method for rescuing ABCA3 deficiency caused by a splicing mutation of ABCA3 in cells, and other human or non-human subjects, comprising using CRISPR/Cas9 to delete a loxP site located at an intronic region of ABCA3 flox. 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.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The claims are drawn to a method for rescuing ABCA3 deficiency caused by a splicing mutation of ABCA3. The method comprises using CRISPR/Cas9 to delete a loxP site located at an intronic region of ABCA3 flox. The nature of the invention is complex in that the splicing mutation of ABCA3 is only capable within the specific Sftpc-Cre; Abca3flox/flox mouse models and not any splicing mutation of ABCA3 of any subject.
Breadth of the claims: The claims broadly encompass the method of rescuing ABCA3 deficiency caused by a splicing mutation of ABCA3. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. Specifically, that any splicing mutation of ABCA3 can be within any subject.
Guidance of the specification and existence of working examples: The specification provides that to develop a therapeutic strategy to rescue ABCA3 deficiency caused by a splicing mutation of ABCA3, they designed an experimental scheme using CRISPR/Cas9 to delete a loxP site located at an intronic region of ABCA3 flox mice (Sftpc-Cre; Abca3flox/flox) (Page 1, Abstract). The specification continues that the inventors attached intein-N terminus and intein-C terminus fragments with N-terminus ABCA3 and C-terminus ABCA3 fragments, respectively, and successfully produced recombined ABCA3 protein in 293T cells in vitro (Page 1, Abstract). The specification provides that the invention would extend the survival rate of ABCA3 deficient mice (Page 1, Abstract). No description is provided of the invention being successful within any subject. No working examples are provided of the invention used within any subject but suggested that the invention would be successful within a mouse model.
Predictability and state of the art: For some relevant background, Rindler et al (JCI Insight. 2017 Dec 21;2(24):e97381; Pgs. 1-14) teaches to identify the role of Abca3 in postnatal lungs, transgenic Sftpc-CreERT2, Abca3flox/flox (Sftpc-CreERT2;Abca3flox/flox) mice were produced, hereafter termed control (Page 2, Paragraph 1). Rindler teaches homozygous Abca3-floxed (Abca3flox/flox) mice were produced wherein the Abca3flox/flox mice have LoxP sites flanking exons 4 and 7 of the Abca3 gene (Page 10, Paragraph 3). Rindler teaches Abca3flox/flox mice were mated to the Sftpc-CreERT2 mice that express a tamoxifen-inducible Cre (IRES-CreERT2) under the control of the Sftpc promoter–generating control mice (Page 10, Paragraph 3).
Besnard et al (Am J Physiol Lung Cell Mol Physiol 298: L646–L659, 2010) teaches "Floxing" is a highly specific, laboratory-designed technique intended to delete (knockout) specific exons when exposed to Cre recombinase -- such as selectively deleting Abca3 in mouse lung cells to study the effects of surfactant deficiency (Page L646, Abstract and Page L647, Column 1 bridging Column 2).
Amount of experimentation necessary: In order to practice the claimed invention, an immense amount of experimentation would be required. As disclosed above, the specification itself provides description of the use of CRISPR/Cas9 to delete a loxP site located at an intronic region of ABCA3 flox mice (Sftpc-Cre;Abca3flox/flox). No description is provided of the invention being successful within any subject. No working examples are provided of the invention used within any subject but suggested that the invention would be successful within a mouse model. Therefore, experiment could be conducted, but in view of the specification there does not appear to be any amount of experimentation that would be sufficient to reliably produce the exact product of the invention. Such experimentation would not be possible due to not having the specific splicing mutation of ABCA3 and the steps of how the ABCA3 flox is created within any subject as well as an ABCA3 deficiency that occurs naturally would not necessarily have loxP sites in the cell genome. Therefore, it would require immense amount of unpredictable experimentation to practice the claimed invention with such variants in the possible result.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claim 1 is not considered to be fully enabled by the instant disclosure.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Peranteau et al (WO 2020/206461 A1).
Regarding claim 1, Peranteau teaches a method of treating a monogenic lung disease in a subject in need thereof comprising editing a gene in a lung cell of the subject using the CRISPR-Cas causing genome editing to remove one or more undesired mutations; and, wherein the Cas9 protein and the guide RNA and said guide strand targets a gene in fetal or post-natal lung, such as ABCA3 (Page 2, line 23 bridging Page 3, line 9). Peranteau teaches delivered Ad vectors containing SpyCas9 and an sgRNA targeting the loxP sites flanking the mT/stop cassette (Ad.mTmG) into the amniotic cavity of gestational day (E) 16 R26mTmG/+ fetuses (Page 4, Fig. 2A-2D Description; Page 25, line 20 bridging Page 26, line 3; Page 31, line 20 bridging Page 32, line 22). Peranteau teaches for the R26mTmG/+ mouse experiments, sgRNAs were designed to target both the loxP sites flanking the mT-tdTomato and stop cassette, causing the edited cells to express EGFP (Page 25, line 20 bridging Page 26, line 3; and Page 27, Lines 9-27), showing that removal of the loxP site prior to the gene was capable of rescuing expression of the gene downstream within lung cells.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Peranteau to include the specific removal of the loxP site in the intron region 5’ of the ABCA3 gene for rescue the gene because Peranteau teaches it is within the ordinary skill in the art to use the Cas9 and sgRNAs to target either side of a loxP site upstream of a fluorescent signal gene in order to remove the loxP and stop codon and rescue or re-activate the fluorescent signal as well as that this system can be translated for use in target genes in fetal or post-natal lung, such as ABCA3.
One would have been motivated to make such a modification in order to receive the expected benefit of rescue of the ABCA3 gene without removal of the gene itself as taught by Peranteau.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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, JENNIFER A DUNSTON can be reached at (571) 272-2916. 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.
/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
Prosecution Insights