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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-15 and 19 in the reply filed on 4/2/26 is acknowledged. The traversal is on the ground(s) that CN114191561A is not properly cited prior art because CN114191561A has an effective filing date of December 15, 2021 and the instant application is a national stage entry filed December 15, 2022 claiming priority to Chinese Patent application 202111533616.1 filed December 15, 2021. This is not found persuasive because Applicant’s priority document is not in the English language and therefore the effective filing date of the claims is only provided the international filing date of 12/15/2022 and the publication date of CN114191561A, which has a different inventive entity, is March 18, 2022, and that is prior to December 15, 2022.
The requirement is still deemed proper and is therefore made FINAL.
Without traverse, Applicant elected the following species for examination:
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Claims 16-18 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/2/26.
Claim Status
Claims 1-20 are pending.
Claims 16-18 and 20 are withdrawn.
Claims 1-15 and 19 are presented for examination as they read upon the elected subject matter.
Priority
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Applicant’s foreign priority document is not in English. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/17/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
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.
Claim 8 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 8 recites: “any type of cells or vesicles”. The addition of the word "type" to an otherwise definite expression (e.g., cells or vesicles) extends the scope of the expression so as to render it indefinite. Ex parte Copenhaver, 109 USPQ 118 (Bd. Pat. App. & Inter. 1955). See MPEP 2173.05(b)(III)(E). Correction is required.
Claim 13 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 13 recites the limitation "the nucleic acid molecule" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 13 is dependent upon claim 9. In searching for antecedent basis for the limitation, the Examiner did not find any basis in claims 1 and 6-9. Therefore, the limitation lacks antecedent basis. Claim 12 recites “a nucleic acid molecule”. Correction is required.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-15 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over CN114191561A (of record).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims an ionizable lipid compound elected species of:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical chemical research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical chemistry and possess specialized knowledge in drug delivery, material science, and organic chemistry to develop pharmaceutical dosage forms. They understand how to select excipients (inactive ingredients), optimize stability and storage, and ensure compliance with regulatory standards (FDA, GMP). Their expertise covers formulation development, dosage form design, and manufacturing processes.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1-5 and 19, CN114191561A teaches synthesis of ionizable lipid compounds of the structure (Page 24 of 32; Example 3) that meets definitions for G3 and G4:
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CN114191561A also teaches using the diamine precursor (Page 22 of 32; Example 2):
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Regarding claims 6 and 12, CN114191561A teaches nucleic acid drug molecules such as one or more of mRNA, siRNA or plasmid DNA in a mass ratio of 1:5-50 (Claims 1-8; Page 12 of 32; 1st paragraph) thus providing a delivery carrier comprising one or more ionizable lipid compounds for the nucleic acid drug molecules.
Regarding claim 7-9, CN114191561A teaches cholesterol as a helper molecule in a molar ratio of 0.1-1:0.1-1 (Claim 7). The final molar ratio at least overlaps the feeding molar ratio.
Regarding claim 10, CN114191561A teaches modification with a targeting substance said targeting substance being one or more of folic acid, a single chain antibody or a targeting polypeptide (Claims 6-7).
Regarding claim 11, CN114191561A teaches an average particle size of 50 nm to 200 nm (Claim 5) and the polydispersity is ≤0.4 (Page 12, bottom).
Regarding claims 13-14, CN114191561A teaches a nucleic acid delivery system further comprising an additive comprising a stabilizer, and/or diluent in an amount of 1-20% of the total mass (Claims 8-9).
Regarding claim 15, CN114191561A teaches intravenous injection of the nucleic acid drug delivery system (Claims 8 and 10). How it is locally administered or administered by intravenous injection are intended uses of the delivery carrier and implicit in the delivery carrier of CN114191561A.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and CN114191561A is that CN114191561A do not expressly teach the elected species ionizable lipid compound. However, 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 disclosure of CN114191561A to produce the elected species ionizable lipid compound, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because it is merely substitution of one diamino compound for another in the synthesis taught by CN114191561A. As noted above, CN114191561A teach a compound with the claims G3 and G4 substituents but synthesized with 1,3-diamino-2-propanol (Step2: Synthesis of Compound 3). CN114191561A also employs another diamino compound 2-(bis(2-aminoethyl)amino)ethan-1-ol (Step 2: Synthesis of Compound 2). It is then obvious to substitute one diamino compound for another in the synthesis to derive the elected species with a reasonable expectation of success. "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). Moreover, “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982). With the disclosure of CN114191561A in front of them, making the diamine substitution to improve upon the prior art is an obvious course of action for the ordinary artisan in this art. “The normal desire of scientists or artisans to improve upon what is already generally known” In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003).
The difference between the instant application and CN114191561A is that CN114191561A do not expressly teach a freeze-dried powder of the delivery carrier. However, lyophilization of solutions to obtain powders is a conventional pharmaceutical technique and the ordinary artisan would freeze dry the mRNA nanolipid particles of Example 4 of CN114191561A to obtain a powder for storage and future experimentation with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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