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 .
Election/Restrictions
Amended claim directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 3 is drawn to a drug delivery composition comprising the neurogenic protein MeCP2, not required by the species of composition elected in the response 5 May 2025, which specified an RNA active agent.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 3 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of Claims
The amendments and arguments filed 3 September 2025 are acknowledged and have been fully considered. Claims 1-5 and 7-23 are currently pending. Claims 1, 3, 7, and 14-15 are amended; claim 6 is cancelled; claims 3-4, 8-13, and 17-23 are withdrawn; no claims are new.
Claims 1-2, 5, 7, and 14-16 are examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. In particular, the rejection of claims under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendment to the claims. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5, 7, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Molinaro et al. (Nature Materials, 2016, Vol. 15, 1037-1047 cited on Applicant’s IDS filed 21 June 2022) in view of Chooi et al. (Biomaterials, 2019, Vol. 197, 327-344).
Claim 1 is drawn to a drug delivery composition comprising a population of biomimetic proteolipid nanovesicles composed of phospholipids and cholesterol, enriched of one or more neuronal-derived membrane fragments, polypeptides, or biologically-active fragments or derivatives thereof, and surrounding an aqueous core; and
further comprising at least one therapeutic agent selected from a group including a chemotherapeutic (more specifically a tumor growth inhibitor (Claim 5)); and
wherein the neuronal-derived membrane fragments comprise at least one cellular-targeting moiety.
Claim 2 is drawn to the drug delivery composition of claim 1, wherein the proteolipid nanovesicles comprise at least one neuronal-derived protein or active fragment thereof, or a combination thereof on their surface.
Molinaro et al. teach bioinspired drug delivery carriers comprising a population of proteolipid vesicles (Abstract). Molinaro et al. further teach these proteolipid vesicles comprising phospholipids, cholesterol, and leukocyte membrane proteins surrounding an aqueous core (Fig. 1c on pg. 1036). Molinaro et al. further teach the proteolipid vesicles encapsulating paclitaxel (Pg. 1040 left column last paragraph).
As such, Molinaro et al. teach a drug delivery composition comprising a population of biomimetic proteolipid vesicles composed of phospholipids and cholesterol, enriched of one or more cell derived polypeptides, and surrounding an aqueous core; further comprising at least one tumor growth inhibitor therapeutic agent (paclitaxel), wherein the proteolipid vesicles comprise at least one cell derived protein on their surface.
The composition of Molinaro et al. differs from the instantly claimed composition in the following way:
the composition of Molinaro et al. does not comprise neuronal derived proteins.
Yet, as to 1: Molinaro et al. teach the leukocyte derived membrane proteins assisting in the targeted delivery of the drug delivery system (Pg. 1037 left column).
Chooi et al. teach the interaction of neurons through cell adhesion molecules (CAMs) including the transmembrane protein L1 cell adhesion molecule (Pg. 327-328 bridging paragraph). Chooi et al. further teach in Table 1 (Pg. 328) various CAM proteins and their related cell interactions. While Chooi et al. do not explicitly teach CAMs as targeting moieties, Chooi et al. do teach that they play a direct role in cell-cell contacts by interacting with the same type of CAM on another cell. This homophilic interaction between CAMs reads on targeting under its broadest reasonable interpretation.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the drug delivery system of Molinaro et al. to include neuronal-derived CAMs. It would have been obvious to combine the known drug delivery system with the known neuron interacting CAMs to yield the predictable result of a drug delivery system capable of targeting neurons, with a reasonable expectation of success.
Based on all of the foregoing, claims 1-2 and 5 are rejected as prima facie obvious.
Claim 7 is drawn to the drug delivery composition of claim 1, wherein degradation of the population of biomimetic proteolipid nanovesicles occurs via enzyme-facilitated biodegradation of one or more of the lipids, the phospholipids, or the cholesterol comprising them.
As discussed in MPEP 2112.01, "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
As Molinaro et al. and Chooi et al. teach all of the structural limitations of the instantly claimed drug delivery composition, the instantly claimed release properties and degradation properties are necessarily present.
As such, claim 7 are rejected as prima facie obvious.
Claim 14 is drawn to the drug delivery composition of claim 1, wherein the biomimetic proteolipid nanovesicles are about 100 to about 1000 nm in average diameter.
Molinaro et al. further teaches the proteolipid vesicles having a homogenous size of about 120nm (Pg. 1038 right column last paragraph), overlapping with the instantly claimed range.
As such, claim 14 is rejected as prima facie obvious.
Claim 15 is drawn to the drug delivery composition of claim 1, wherein the synthetic phospholipids are selected from the group including 1,2-dioleoyl-sn-glycerophosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycerophosphocholine (DPPC), and 1,2-distearoyl-sn-glycerophosphocholine (DSPC).
Molinaro et al. further teach the proteolipid vesicles comprising DPPC, DSPC, DOPC, and Cholesterol (Fig. 1b-c).
As such, claim 15 is rejected as prima facie obvious.
Claim 16 is drawn to the drug delivery composition of claim 1, wherein the lipid-to-protein ratio is from about 160 to 5 (wt/wt) to about 300:1.
Molinaro et al. further teach the proteolipid vesicles having a lipid-to-protein ratio from 100:1 to 600:1, overlapping with the instantly claimed range.
As such, claim 16 is rejected as prima facie obvious.
Claim 5 is ADDITIONALLY rejected under 35 U.S.C. 103 as being unpatentable over Molinaro et al. and Chooi et al. as applied to claims 1-3, 5-7, and 14-16 above, and further in view of Sah (Life Sciences, 2006, Vol. 79, 1773-1780).
The teachings of Molinaro et al. and Chooi et al. have been set forth above.
Claim 5 is drawn to the drug delivery composition of claim 1, wherein the therapeutic agent is an RNA molecule (Applicant’s elected species).
Molinaro et al. and Chooi et al. do not teach the drug delivery composition comprising applicant’s elected species of an RNA molecule.
However, Molinaro et al. teach the proteolipid vesicles encapsulating hydrophilic, amphiphilic, and hydrophobic drug molecules (Pg. 1040 left to right column bridging paragraph), indicating that the therapeutic agents that can be encapsulated is not particularly limited.
Sah teaches the use of small interfering RNA molecules as treatment for neurological disorders (Abstract). Sah further teaches various in vivo RNA interference in neurons for therapeutic purposes (Table 1 on pg. 1775).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the drug delivery system of Molinaro et al. and Chooi et al. to encapsulate RNA as taught by Sah. It would have been obvious to combine the known drug delivery system with the known therapeutic capability of RNA in neurons to yield the predictable result of a targeted drug delivery system for delivery of RNA to neurons, with a reasonable expectation of success.
As such, claim 5 is rejected as prima facie obvious.
Claim 15 is ADDITIONALLY rejected under 35 U.S.C. 103 as being unpatentable over Molinaro et al. and Chooi et al. as applied to claims 1-3, 5-7, and 14-16 above, and further in view of Dos Santos et al. (BBA Biomembranes, 2007, Vol. 1768, 1367-1377).
The teachings of Molinaro et al. and Chooi et al. have been set forth above.
Claim 15 is drawn to the drug delivery composition of claim 1, wherein the synthetic phospholipid is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine N-[carboxy(polyethylene glycol)-2000] (DSPE-PEG2000) (Applicant’s elected species).
Molinaro et al. and Chooi et al. do not teach applicant’s elected species of DSPE-PEG2000.
However, Dos Santos et al. teach that the inclusion of DSPE-PEG2000 in a lipid membrane improves the plasma circulation time of liposomes (Abstract).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Molinaro et al. and Chooi et al. to include DSPE-PEG2000. It would have been obvious to use the known technique of including DSPE-PEG2000 in a lipid membrane to improve the drug delivery composition of Molinaro et al. and Chooi et al. in the same way by improving plasma circulation time, with a reasonable expectation of success.
As such, claim 15 is rejected as prima facie obvious.
Response to Arguments
Applicant's arguments filed 3 September 2025 have been fully considered but they are not persuasive.
Applicant argues on pg. 9 of the remarks that there is no teaching in Chooi et al. regarding the use of neuronal-derived membrane fragments for targeted delivery.
This argument is not persuasive. Molinaro et al. teach that bioinspired delivery systems can achieve targeted delivery by surface functionalization with membrane ligands, such as proteins (Pg. 1037 left column), indicating that many different membrane components are suitable for enhancing targeted delivery of the biomimetic vesicles. While Chooi et al. does not explicitly teach neuronal-derived membrane fragments for targeted delivery, Chooi et al. do teach that cell-cell interactions between neurons are mediated via cell adhesion molecules, which are transmembrane proteins that cause cell contacts through homophilic interactions (Pg. 327 right column last paragraph). One of ordinary skill in the art would understand that the homophilic interactions between neuronal CAMs is very similar to the targeting proteins utilized by Molinaro et al., and inclusion of the neuronal CAMs would lead to a drug delivery system capable of targeting neurons, with a reasonable expectation of success.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Paul Hoerner whose telephone number is (571)270-0259. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm eastern.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/PAUL HOERNER/ Examiner, Art Unit 1611