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 Status
Claims 18-27 are pending and examined on the merits.
Claim Objections
Claim 27 is objected to because of the following informalities: line 1 of the claim recites, “plant derived particles” when is should instead recite “plant-derived lipid particles.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
Indefiniteness
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.
Claim 25 is 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 pre-AIA the applicant regards as the invention.
Claim 25 requires that the lipid particles used in the method have a zeta potential greater than -20 mV. Smith et al 2017 (Anal Bioanal Chem 409: p. 5779-5787) teach that liposomes of the same compositions can have greatly different zeta potentials based on the pH and the presence of ions in the environment in which they reside (Figure 2A-2B). Given this variability and the claim not specifying either pH or ion concentration of the buffer in which the liposomes are present, the metes and bounds of the claims cannot be determined.
Claim Rejections - 35 USC § 103
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(s) 18-22 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Sammons et al (US 9988634 B2) and further in view of Wang et al 2013 (Nature Communications 4:1867 p. 1-11), Zhang et al (US 2016/0208243 A1).
Sammons et al teach methods of controlling gene expression in a plant by introducing to the exterior surface of a plant a double stranded RNA (including siRNA) with a transferring agent including an organosilicone surfactant or a cationic lipid (claim 1, columns 17, 22, 75).
Sammons et al do not teach plant-derived lipid particles.
Wang et al teach grapefruit-derived lipid nanoparticles to deliver nucleic acids including RNAs into cells.
Zhang et al teach CRISPR based genome modification of target cells including plant cells. In such methods gRNAs direct the CRISPR nuclease to target sequence in the genome. They also teach gRNA-nuclease complexes which are taught many places in the reference (Paragraph 1124). They also contemplate use of liposomes to introduce the CRISPR system (paragraphs 1044-1045). They also state, “It will be appreciated that reference made herein to particles or nanoparticles can be interchangeable,” and that the cationic lipid DOTAP can be part of the particle (paragraph 707). Additionally, they teach that the genome editing methods can be used to confer herbicide tolerance to a plant (paragraph 1127).
At the time filing, it would have been prima facie obvious to use the grapefruit derived nanoparticles of Wang et al to delivery RNA onto plants in methods such as those taught by Sammons et al. Further, a person of ordinary skill in the art would have been motivated to add a cationic lipid, such as DOTAP taught by Zhang et al, to the formulation as they are well-known to stabilize RNA for cellular delivery. A person of ordinary skill in the art would have recognized that such a method could be used to delivery any nucleic acid including gRNAs used in genome editing such as to the end of conferring herbicide tolerance to a plant as taught by Zhang et al. As such, claims 18-22 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Sammons et al and Wang et al, and Zhang et al.
Claim(s) 23 is rejected under 35 U.S.C. 103 as being unpatentable over Matthews et al 1981 (Planta 153: p. 90-94) and further in view of Wang et al 2013 (Nature Communications 4:1867 p. 1-11), Zhang et al (US 2016/0208243 A1) , and Sammons et al (US 9988634 B2) as applied to claims 18-22 and 26 and further in view of Du et al 2014 (Scientific Reports 4: p. 7107-7113).
The claims are drawn to the method of claim 22 wherein cationic lipid is 25-40% DOTAP.
Sammons et al and Wang et al, Zhang et al collectively teach all the limitations of claim 1.
Sammons et al and Wang et al, Zhang et al collectively do not teach the concentration of DOTAP.
Du et al teach using the cationic lipid DOTAP to deliver nucleic acids to a cell. They also teach that the liposomes were formulated at weight ratios including 0.5:1 which is the same as 1:2 which is 33.3%
At the time of filing, it would have been prima facie obvious to a person of ordinary skill in the art to use DOTAP at the concentration taught by Du et la as the cationic lipid to deliver siRNA to a cell in the method of Sammons et al and Wang et al, Zhang et al. A person of ordinary skill in the art would have been motivated to use DOTAP at the claimed concentration given that Du et al teach that the DOTAP can be used as a cationic lipid in liposomes for nucleic acid delivery to a cell. As such, claim 23 is rejected as being obvious.
Claim(s) 24 is rejected under 35 U.S.C. 103 as being unpatentable over Matthews et al 1981 (Planta 153: p. 90-94) and further in view of Wang et al 2013 (Nature Communications 4:1867 p. 1-11), Zhang et al (US 2016/0208243 A1), and Sammons et al (US 9988634 B2) as applied to claims 18-22 and 26 and further in view of Zhang et al 2010 (International Journal of Pharmaceutics 390: p.198-207).
The claims are drawn to the method of claim 22 wherein cationic lipid is 20-40% DC-cholesterol.
Sammons et al and Wang et al, Zhang et al teach all the limitations of claim 1.
Sammons et al and Wang et al, Zhang et al teach do not teach DC-cholesterol.
Zhang et al teach using the cationic lipid DC-cholesterol to deliver siRNAs to a cell. It appears that in preparing the liposomes Zhang et al used a 1:1:1 ratio between three different lipids (See Preparation of DC-Chol/DOPE liposomes, p. 199). Further, note that Zhang et al varied the amount of DC-Chol in its different experiments (Figures 1, 2, and 7-10).
At the time of filing, it would have been prima facie obvious to a person of ordinary skill in the art to use DC-cholesterol as the cationic lipid to deliver siRNA to a cell in the method collectively taught by Sammons et al and Wang et al, Zhang et al. A person of ordinary skill in the art would have been motivated to use DC-cholesterol given that Zhang et al teach that the DC-cholesterol can be used as a cationic lipid in liposomes for nucleic acid delivery to a cell. Even if the exact Zhang et al did not use DC-Chol within the exact claimed range, it is the position of The Office that an improvement in results obtained from using the claimed range is required to render claim 18 non-obvious. As such, claim 24 is rejected as being obvious.
Claim(s) 25 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Matthews et al 1981 (Planta 153: p. 90-94) and further in view of Wang et al 2013 (Nature Communications 4:1867 p. 1-11), Zhang et al (US 2016/0208243 A1) , and Sammons et al (US 9988634 B2) as applied to claims 18-22 and 26 and further in view of Smith et al 2017 (Anal Bioanal Chem 409: p. 5779-5787).
Claim 25 is drawn to the method of claim 20 wherein the plant derived lipid particles have a zeta potential of greater than -20mV. Claim 27 is drawn to the method of claim 18 wherein the plant-derived lipid particles have a median size of between 89 to 104 nm.
Sammons et al and Wang et al, Zhang et al collectively teach all the limitations of claims 18 and 22.
Sammons et al and Wang et al, Zhang et al collectively do not teach that the plant derived lipid particles have a zeta potential of greater than -20mV or have a median size of between 89 to 104 nm.
Smith et al teach that zeta potential of liposomes is largely controlled pH and ionic strength, particularly the presence of cationic vs anionic lipids.
At the time of filing, it would have been prima facie obvious to a person of ordinary skill in the art to vary the concentration of the cationic lipids and the size of the liposome to the end of optimizing efficiency of delivery of the nucleic acid (siRNA) the plant cell in absence of any evidence to the contrary. As such, claims 25 and 27 are rejected as being obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW R KEOGH whose telephone number is (571)272-2960. The examiner can normally be reached M-Th 7-4:30, half day on Fridays.
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, Amjad Abraham can be reached on 571-270-7058. 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.
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
Prosecution Insights