DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment and response filed on 4/13/2026 have been received and entered into the case. Claims 2, 5 and 10 have been canceled. Claims 1, 3-4, 6-9 and 11-20 are pending, Claims 8, 11-15 and 19-20 have been withdrawn, and Claims 1, 3-4, 6-7, 9 and 16-18 have been considered on the merits, insofar as they read on the elected species of a double mutant W235R and R275S tPA. All arguments have been fully considered.
Withdrawn Rejections
Rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of applicant’s amendments.
Rejections of Claims 1-7, 9 and 16-18 under 35 U.S.C. 103 as being unpatentable over Vivien et al (WO 2013/034710 A1; 3/14/2013.) in view of Giuliano et al (Medicines. 2019;6(7):1-20.) are withdrawn in view of applicant’s amendments.
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.
Claims 3-4 are 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 3, line 1-2, the recitation of “said poloxamer” is indefinite. Claim 3 is dependent from claim 1, and claim 1 recites the nanoparticle comprises a poloxamer and the thermoreversible polymer is a poloxamer. It is unclear which poloxamer claim 3 is referring to, the nanoparticle or the thermoreversible polymer?
Claim 4 (line 1) recite “according to claim 2”. However, claim 2 has been canceled. Hence, claim 4 is dependent upon a canceled claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-4 and 6 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Ingber et al (US 2015/0147276 A1; 5/28/2015.).
The instant claims recite a composition comprising a thermoreversible polymer and a nanoparticle comprising a plasminogen activator and a poloxamer and wherein said thermoreversible polymer is a poloxamer.
Ingber teaches compositions for treating thrombotic disorders and internal hemorrhage (Abstract), comprising a mix of nanoparticles (para 0027) comprise poloxamers such as 407 (a thermoreversible polymer) and 188 (para 0075, 0355) and plasminogen activator (para 0143).
Therefore the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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.
Claims 7 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al (US 2015/0147276 A1; 5/28/2015.) as applied to claims 1, 3-4, 6 above, further in view of Giuliano et al (Medicines. 2019;6(7):1-20.).
Ingber does not teach the claimed concentration of poloxamer 407 (claims 7 and 16-17).
However, Ingber does teach said compositions comprise poloxamers such as 407. Giuliano teaches poloxamer 407 has been widely studied as a potential biomaterial for obtaining thermos-sensitive hydrogels thanks to its solubilizing capacity, low toxicity, drug release characteristics, and compatibility with numerous biomolecules and excipients (p.2 para 2). Solutions of poloxamer 407 at copolymer concentrations of 15-30% w/w have a low critical solution temperature similar to that of normal body temperature so they can easily be injected with a needle and syringe due to the initial low viscosity and will then promote the controlled release of an encapsulated drug by means of the gelation process (p.3 para 3). Poloxamer 407 is often used in association with other poloxamers, especially with poloxamer 188, in order to modulate the sol-gel transition temperature (p.3 para 6). Poloxamer 407-based hydrogels are attractive pharmaceutical formulations for medical application, the peculiar thermos-reversible behavior they exhibit makes poloxamer 407-based hydrogels suitable and versatile pharmaceutical formulations (p.12 para 4).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to optimize the concentration of poloxamer 407 as a matter of routine experimentation. Generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. (MPEP 2144.05 II) Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference and routine practice to incorporate an optimized amount of poloxamer 407 with a reasonable expectation for successfully obtaining a composition.
Claims 9 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al (US 2015/0147276 A1; 5/28/2015.) as applied to claims 1, 3-4, 6 above, further in view of Vivien et al (WO 2013/034710 A1; 3/14/2013.).
Ingber does not teach the claimed plasminogen activator (claims 9 and 18).
However, Ingber does teach said compositions can be used for treating thrombotic disorders and internal hemorrhage (Abstract), and said compositions comprise plasminogen activator, wherein said plasminogen activator includes hybrids, fragments and mutants (para 0143). Vivien teaches mutated plasminogen activators for treating thrombotic and haemorrhagic diseases (p.1 line 5-6), wherein said mutant is a double mutation W253R and R275S (a plasminogen activator) (p.11 line 4-5, line 15 line 22-23). Note: Sequence is listed in Search results filed on 10/6/2025, 20251006_100604_us-17-998-432-1.rag file, Result 1, see below.
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Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate plasminogen activator that is a double mutant W253R and R275S tPA having a sequence set forth as SEQ ID NO: 1, since Ingber and Vivien both disclose compositions for treating thrombotic disorders and hemorrhage, Ingber discloses said compositions comprise mutated plasminogen activator, and Vivien discloses said compositions comprise a double mutation W253R and R275S plasminogen activator having a sequence set forth as SEQ ID NO: 1. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to incorporate plasminogen activator that is a double mutant W253R and R275S tPA having a sequence set forth as SEQ ID NO: 1, with a reasonable expectation for successfully obtaining a composition.
Response to Arguments
Applicant argues that the present invention provides a two-step formulation strategy for plasminogen activators: nanoprecipitation of the plasminogen activator into poloxamer, followed by resuspension of these nanoparticles in a thermoreversible poloxamer gel, and that none of the cited documents discloses (i) nanoprecipitating a plasminogen activator into a poloxamer and (ii) resuspending it in a thermoreversible poloxamer gel. However, these arguments are moot since those rejections are withdrawn in view of applicant’s amendments. It is also noted that the rejected claims are directed to a composition, not a method.
Conclusion
No claims are 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 extension fee 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Curtis Mayes can be reached on (571)272-1234. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759
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