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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 4/9/2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 6/19/2024 is acknowledged.
Claim 16-21 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II-III, there being no allowable generic or linking claim.
Status of Claims
Cancelled: 1, 9-14, 22-25
Withdrawn: 16-21
Examined Herein: 2-8, 15
Priority
Priority to PRO 62/798,137 filed on 1/29/2019 and PCT/US2020/015677 filed on 1/29/2020 is
acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/3/2022 and 12/11/2023 is in
compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is
being considered by the examiner.
Drawings
The drawings filed on 7/13/2021 are accepted.
Withdrawn Rejections
The objection over the phrase "tritratable" is hereby withdrawn in view of Applicant’s amendments to claim 2, which removes the phrase. [Remarks 4/9/2026, Page 7]
The rejection of claims 2, 5-7 and 15 under 35 U.S.C. 103 over Lam, Petersen, and Miller are hereby withdrawn in view of Applicant’s amendments to claim 2. [Remarks 4/9/2026, Page 8]
The rejection of claims 2-8 and 15 under 35 U.S.C. 103 over Lam, Petersen, Miller, and Annenkov are hereby withdrawn in view of Applicant’s amendments to claim 2. [Remarks 4/9/2026, Page 8]
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.
Claims 2-8 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Cullis (US 2004/0241855 A1, Published 12/2/2004), in view of Kahl (US 2003/0175413 A1, Published 9/18/2003) and Sgouros (US 2004/0166060 A1, Published 8/26/2004).
With respect to claim 2, Cullis discloses a lipid-based nanocarrier having the following structure:
PNG
media_image1.png
337
1644
media_image1.png
Greyscale
[Cullis, Figure 2(a), DSPE-CPL-1]
wherein,
n is about 45-114 (PEG2000 - PEG5000); [Cullis, 0137]
R1 is -NH2;
R2 and R3 are each independently the same fatty acid. [Cullis, Figure 2(a), DSPE-CPL-1]
Cullis further discloses -NH2 may alternatively be a single protonizable cationic head group. [Cullis, 0121] Moreover, Cullis discloses the lipid-based nanocarrier comprises radioactive diagnostic markers. [Cullis, 0177-0180]
With respect to claim 5, Cullis discloses the PEG linker may be selected from PEG(2000), PEG(3000), PEG(3350), or PEG(4000). [Cullis, 0137]
With respect to claim 6, Cullis discloses the PEG linker may be PEG(2000). [Cullis, 0137]
With respect to claim 7, Cullis discloses R2 and R3 are stearic acid. [Cullis, Figure 28C]
With respect to claim 15, Cullis discloses a pharmaceutical formulation comprising the structure and a pharmaceutically acceptable carrier. [Cullis, 0186]
Cullis does not disclose R1 is a moiety having the claimed structure, the lipid-based nanocarrier adheres to an extracellular matrix (ECM) of a target cell or tumor, the internalization of the lipid-based nanocarrier by the target cell is minimized, or the lipid-based nanocarrier comprises a DOTA chelating agent comprising 225Ac.
However, with respect to claim 2, 3, 4, and 8, Kahl discloses a cationic phospholipid comprising dimethyl-ammonium propane (DAP) as a protonizable cationic head group. [Kahl, 0020]
Moreover, with respect to claim 2, Sgouros discloses a liposome comprising (or entrapping) an alpha particle-emitting radio marker, 225Ac-DOTA. [Sgouros, 0026, 0077, 0127, 0128]
Modifying the nanocarrier disclosed by Cullis by replacing the -NH2 headgroup with DAP and selecting 225Ac-DOTA as the diagnostic marker comprised within, results in the nanocarrier of claim 1 and 8:
PNG
media_image2.png
334
1479
media_image2.png
Greyscale
[Structure edited by the Examiner and depicts the aforementioned modification of the nanocarrier disclosed by Cullis. This depiction is for illustrative purposes only.]
wherein,
n is about 45-114 (PEG2000 - PEG5000) [Cullis, 0137]
R1 is DAP, or a moiety having a single titratable cationic charge having a structure of:
PNG
media_image3.png
179
103
media_image3.png
Greyscale
R2 and R3 are each independently stearic acid. [Cullis, Figure 2(a), DSPE-CPL-1]
In which case, with respect to claims 2 and 3, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. MPEP 2112.01. The combination of the prior art teaches DAP and the claimed lipid-based nanocarrier. Thus, R1 necessarily becomes positively charged under a physiological pH of a tumor interstitium and has an intrinsic pKa from about 6.0 to about 6.9, the modified lipid based nanocarrier necessarily adheres to an extracellular matrix (ECM) of a target cell or tumor and the internalization of the lipid-based nanocarrier by the target cell is necessarily minimized.
It would be obvious to one of ordinary skill in the art to modify the nanocarrier disclosed by Cullis by replacing the -NH2 headgroup with DAP and have a reasonable expectation of success. Cullis discloses a lipid-based nanocarrier, DSPE-PEG-NH2, comprising an amide headgroup. Cullis further discloses DSPE-PEG-NH2 may alternatively comprise one protonizable cationic head group. Kahl discloses a cationic phospholipid comprising dimethyl-ammonium propane (DAP) as a protonizable cationic head group. Thus, Kahl establishes that DAP is a known protonizable cationic head group suitable for incorporation into lipid compounds. Accordingly, the combined teachings of Cullis and Kahl suggest that DAP may serve as the protonizable cationic head group in the lipid-based nanocarrier disclosed by Cullis. One would have been motivated to do so because the selection of a known material based on its suitability for its intended use is prima facie obvious. MPEP 2144.07. In the instant case, the selection of DAP based on its suitability for use as a protonizable cationic head group in the lipid-based nanocarrier disclosed by Cullis is prima facie obvious.
It would be obvious to one of ordinary skill in the art to modify the nanocarrier disclosed by Cullis by selecting 225Ac-DOTA as the diagnostic marker comprised within and have a reasonable expectation of success. Cullis discloses a lipid-based nanocarrier, DSPE-PEG-NH2, comprising radioactive markers Sgourous discloses a liposome comprising (or entrapping) an alpha particle-emitting radioactive marker, 225Ac-DOTA. Sgourous discloses 225Ac-DOTA is a known radioactive marker that may be comprised within a lipid-based nanocarrier. Accordingly, the combined teachings of Cullis and Sgourous suggest that 225Ac-DOTA may function as the radioactive marker comprised within the lipid-based nanocarrier disclosed by Cullis. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the instant case, Cullis discloses labeling the nanocarrier with a radioisotope enables the nanocarrier to be used for purposes of in vivo diagnosis. [Cullis, 0178, 0180] Therefore, one would have been motivated by the expectation that the selecting a radioactive marker, like 225Ac-DOTA, as the diagnostic marker would enable the nanocarrier disclosed by Cullis to be used for purposes of in vivo diagnosis.
Response to Arguments
Applicant’s arguments, filed 4/9/2026, with respect to the pending claims over Lam, Petersen, and Miller have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant asserts “Applicant notes that Lam does appear to disclose a liposome containing a single positive charge, e.g., DSPE-CPL-1, but this compound appears to be an intermediate, see Lam, FIG. 21A, and was not further tested or otherwise utilized for transfecting a cell.” [Remarks 4/9/2026, Page 9, Paragraph 2]
DSPE-CPL-1 is not an intermediate. Cullis consistently treats the compound as a final composition. For example, Cullis describes the compound’s synthesis and subsequent evaluation of the product, thereby indicating the compound is a final product, rather than an intermediate. [Cullis, 0194, 0200-0202] The use of the compound for a particular application, such as for transfecting cells, is not dispositive of whether the compound constitutes a final product or an intermediate. The mere fact that the compound may subsequently be employed as a reactant in another synthesis does not establish that the compound is an intermediate or negate Cullis’ characterization of the compound as a final product.
Oath/Declaration
The declaration under 37 CFR 1.132 filed 4/9/2026 is insufficient to overcome the rejection of the pending claims based upon 35 U.S.C. 103 as set forth in the last Office action because the crux of the arguments made are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Moreover, the declaration largely includes statements which amount to an affirmation that the claimed subject matter functions as it was intended to function. This is not relevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof. See MPEP § 716.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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