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
Applicant’s election without traverse of Group II in the reply filed on March 14, 2025 is acknowledged.
The requirement is deemed proper and is therefore made FINAL.
Claims 1-3 and 7-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
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.
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 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kanazawa et al. (Pharmaceutical Research 2011 28:2130-2139 - previously cited) in view of Skoog (previously cited) as evidenced by Tanaka et al. (International Journal of Pharmaceutics 2010 396:229-238).
Kanazawa et al. teach a diblock copolymer of methoxy polyethylene glycol (MPEG) , which is its hydrophilic block, and polycaprolactone (PCL) which is its hydrophobic polyester block (see page 2132 first column second full paragraph). Bound to the hydroxyl end of the polycaprolactone block is the Tat-G peptide which corresponds to instant SEQ ID NO: 1 (see table I, page 2132 first column first full paragraph and instant paragraph 102). Kanazawa et al. teach that the MPEG block has a number average molecular weight of 2000 and the diblock has a molecular weight, as determined by NMR, of 3940 (see page 2131 first column last partial paragraph and page133 second column second full paragraph; instant claim 10). They detail that the characterization was conducted as in Tanaka at al., who detail a MPEG-PCL diblock with the same MPEG molecular weight and an overall number average molecular weight that were provided by NMR (see page133 second column second full paragraph and Tanaka et al. table 2). Thus the hydrophobic polyester block provided by the PCL has a number average molecular weight of 1940 (see instant claim 10). They generally teach nanoparticle encapsulation of drugs for intranasal delivery to the central nervous system (see page 2130 second column). The polymers are taught to form nanosized micelles and are envisioned as carriers for drug delivery to the brain via nasal administration (see abstract and page 2131 first column second full paragraph; instant claims 10 and 12). Intranasal administration of model drug loaded nano-sized micelles yields far greater localization of the nanosized micelles in the brain and lung tissues than more remote body locales (see figure 1). Treatment of a particular spinal cord disease/condition is not detailed.
Skoog teaches nasally administering neurotrophic agents to the central nervous system in order to treat central nervous system conditions (see abstract and page 2 lines 2-9 and page 4 lines 28-32 and example 7). They additionally teach the method to treat spinal cord disease (see page 27 lines 17-28). The agents are taught to treat a disease or injury of the brain or spinal cord (see page 27 lines 17-18; instant claims 10-11). Compositions include carriers for the neurotrophic agents, where Skoog envisions polyethylene glycol as a component and also envisions emulsions as a form (see page 20 lines 9-13 and page 23 lines 1-2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat a disease of the spinal cord and specifically spinal cord injury by intranasally administering the composition of Kanazawa et al., where its nanosized micelles encapsulate a neurotrophic agent as detailed by Skoog. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g., specific central nervous system disease vs generic central nervous system disease; specific central nervous system acting drug vs generic central nervous system acting drug). Since Skoog contemplates delivery of their compounds via emulsions and the composition of Kanazawa et al. is an emulsion that is delivered to the central nervous system nasally, there would have been a reasonable expectation of success for the modified method. Therefore claims 10-12 are obvious over Kanazawa et al. in view of Skoog as evidenced by Tanaka et al.
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kanazawa et al. in view of Aloe et al. (previously cited) as evidenced by Tanaka et al.
Kanazawa et al. teach a diblock copolymer of MPEG , which is its hydrophilic block, and PCL which is its hydrophobic polyester block (see page 2132 first column second full paragraph). Bound to the hydroxyl end of the polycaprolactone block is the Tat-G peptide which corresponds to instant SEQ ID NO: 1 (see table I, page 2132 first column first full paragraph and instant paragraph 102). Kanazawa et al. teach that the MPEG block has a number average molecular weight of 2000 and the diblock has a molecular weight, as determined by NMR, of 3940 (see page 2131 first column last partial paragraph and page133 second column second full paragraph; instant claim 10). They detail that the characterization was conducted as in Tanaka at al., who detail a MPEG-PCL diblock with the same MPEG molecular weight and an overall number average molecular weight that were provided by NMR (see page133 second column second full paragraph and Tanaka et al. table 2). Thus the hydrophobic polyester block provided by the PCL has a number average molecular weight of 1940 (see instant claim 10). They generally teach nanoparticle encapsulation of drugs for intranasal delivery to the central nervous system (see page 2130 second column). The polymers are taught to form nanosized micelles and are envisioned as carriers for drug delivery to the brain via nasal administration (see abstract and page 2131 first column second full paragraph; instant claims 10 and 12). Intranasal administration of model drug loaded nano-sized micelles yields far greater localization of the nanosized micelles in the brain and lung tissues than more remote body locales (see figure 1). Treatment of a particular spinal cord disease/condition is not detailed.
Aloe et al. teach nasally administering nerve growth factor to treat spinal cord injury in a subject (see abstract; instant claims 10-11). The treatment is effective at improving motor function after a spinal cord injury (see figure 2A and page 1026-page 1028 first column first full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat spinal cord injury by intranasally administering the composition of Kanazawa et al., where its nanosized micelles encapsulate nerve growth factor, as detailed by Aloe et al.. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g. specific central nervous system disease vs generic central nervous system disease; specific central nervous system acting drug vs generic central nervous system acting drug). Therefore claims 10-12 are obvious over Kanazawa et al. in view of Aloe et al. as evidenced by Tanaka et al.
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kanazawa B (Yakugaku Zasshi 2018 138:443-450 - previously cited) in view of Tanaka et al. and Aloe et al.
Kanazawa B teach treating diseases of the central nervous system by delivering a drug intranasally via nano-sized micelles (see abstract page 444 second column last partial paragraph-page 445 first column first paragraph and page 449 first column). Kanazawa B further discloses a diblock copolymer of methoxy polyethylene glycol, which is its hydrophilic block, and polycaprolactone which is its hydrophobic block as the constituent component of the micelles (see figure 1). They reference their previous work detailed by Tanaka et al. concerning the preparation of these polymers (see page 445 first column). Bound to the hydroxyl end of the polycaprolactone block is the Tat-G peptide which corresponds to instant SEQ ID NO: 1 (figure 1 and instant paragraph 102). The nano-sized micelles are disclosed as being delivered to the cerebrospinal fluid upon intranasal administration (see page 447). The spinal cord is part of the central nervous, thus diseases of the central nervous system embrace those of the spinal cord (see page 444 first column). Treatment of a particular spial cord disease/condition is not detailed.
Tanaka et al. teach at the preparation of MPEG-PCL diblock copolymers for use as micelle carriers for drug delivery into cells (see abstract and page 233-234). The MPEG block has a number average molecular weight of 2000 and the diblock has a number average molecular weight, as determined by NMR, of 3940 (see page 230 first column last full paragraph-page 232 first column first partial paragraph and table 2). Thus the hydrophobic polyester block provided by the PCL has a number average molecular weight of 1940 (see instant claim 10).
Aloe et al. teaches nasally administering nerve growth factor to treat spinal cord injury in a subject (see abstract; instant claims 10-11). The treatment is effective at improving motor function after a spinal cord injury (see figure 2A and page 1026-page 1028 first column first full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the polymer of Tanaka et al. as the MPEG-PCL diblock copolymer of Kanazawa B because Kanazawa B reference it as the source of the polymer they use. It additionally would have been obvious to treat spinal cord injury by intranasally administering the composition of Kanazawa B, where its nanosized micelles encapsulate nerve growth factor as detailed by Aloe et al.. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g., specific central nervous system disease vs generic central nervous system disease; specific central nervous system acting drug vs generic central nervous system acting drug). Therefore claims 10-12 are obvious over Kanazawa B in view of Tanaka et al. and Aloe et al.
Response to Arguments
Applicant's arguments filed July 10, 2025 have been fully considered. In light of the amendment, the rejection over Kanazawa B as a sole relied upon reference are hereby withdrawn. New or modified grounds of rejection are detailed to address the new limitations. The applicant’s arguments are not persuasive.
The applicant acknowledges that Tat is employed purposefully as a name of a category of peptides and as a name for a particular peptide within the category in the disclosure.
The applicant argues that Skoog and Aloe et al. do not teach the claimed polymer. These are secondary references employed to separately support the addition of particular drugs to Kanazawa et al., who already addresses the molecular weight of its Tat modified MPEG-PCL polymer for intranasal delivery to the central nervous system. Kanazawa et al. explicitly teach the polymer to have a claimed MPEG number average molecular weight. They also teach a molecular weight for the total polymer as well as the employed measurement technique that implicitly categorizes the measurement as a number average molecular weight which yields a polyester block with a molecular weight in the claimed range.
The applicant also argues that the claimed method produces unexpected results of increased distribution of the drug cargo to the spinal cord as compared to other tissues. While there is a difference between the amount of increase in dextran uptake from dextran solution as compared to dextran uptake from a MPEG-PCL-Tat carrier in the spinal cord as compared to other central nervous system tissues, it is not clear that the outcome is unexpected to an significant degree. The applicant does not establish the expected outcome for the measured uptake. It is noted that there is a quite a bit of difference in dextran uptake from solution in the olfactory bulb as compared to the spinal cord. Other studies exploring intranasal delivery to regions of the central nervous system did not seem to mirror this difference. This makes drawing conclusions about the claimed copolymer’s impact challenging. For example, Thorne et al. examine the distribution of insulin-like growth factor-I in various sections of the central nervous system 30 minutes after intranasal delivery from solution (see Neuroscience 2004 127:481-496). They assessed the cervical, thoracic, and lumbosacral regions of the spinal cord separately (see table 2). Collapsing these separate measures into a single spinal cord value based on the proportionate size of these regions, given the number of nerves that feed them (8 for cervical, 13 fore thoracic, 6 for lumbar, and 4 for sacral), yields a concentration of 0.7084, while the olfactory bulb yielded 3.42 (see Harrison et al. NeuroImage 2013 68:22-29, page 25 second column fust full paragraph). The spinal cord had an uptake concentration that was 21% of the olfactory bulb uptake concentration. Similarly, Chung et al. examined the uptake of targeted and untargeted nanoparticle carriers into central nervous system tissues after intranasal administration (Pharmaceutics 2020 12(2)(93):1-16). At 30 minutes after administration, the spinal cord had an uptake concentration that was 25% of the olfactory bulb uptake concentration and at 2 hours after administration, the spinal cord had an uptake concentration that was 19% of the olfactory bulb uptake concentration. The applicant produced a spinal cord uptake concentration that was 2% of the olfactory bulb uptake concentration. The applicant’s distribution values from intranasal delivery are quite different than both Thorne et al. and Cheng et al. who achieve values similar to one another. Thus it is unclear that the instantly claimed polymer improves upon the delivery of its cargo to the spinal cord to an unexpectedly superior degree as compared to other tissues since they do not establish their expected outcome and the baseline performance of their test composition deviates from what others have achieved.
Further, even if the tested polymer performed to an unexpectedly superior degree, the applicant has not connected the performance of this single MPEG-PCL block copolymer to the full scope of claimed block copolymers. Thus the showing also is not commensurate in scope with the claims.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
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/CARALYNNE E HELM/Examiner, Art Unit 1615
/MELISSA S MERCIER/Primary Examiner, Art Unit 1615