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 .
Status of Claims
Claims 33-49 filed 12/26/2024 are pending and are the subject of the present Official action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 62/242,580 and PCT/US2016/057092 filed on 10/16/2015 and 10/14/2016, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 10/16/2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/26/2024 was received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
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, 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 33-49 are rejected under 35 U.S.C. 103 as being unpatentable over Takanobu et al. JP2015/047125A, published 3/16/2015 (hereinafter Takanobu) in view of Wang et al. "Ex vivo programmed macrophages ameliorate experimental chronic inflammatory renal disease." Kidney international 72.3 (2007): 290-299 (hereinafter Wang) and Vunjak et al. WO 2015/031376A1, published 3/5/2015 (hereinafter Vunjak).
Claims 33-35, 41 and 49: Takanobu teaches a method for treating wounds comprising administering exogenous M1 macrophages and exogenous M2 macrophages (Takanobu, pg 4, para 11). Although Takanobu describes administering exogenous M1 and M2 macrophages, Takanobu does not describe the sequential administration of exogenous M1 and M2 macrophages separated by a period of at least 1 day and not more than 2 days as described in claim 33. Takanobu does not describe that the M1 and M2 administration steps may be divided into at least two further subsequent administration steps or the specific administration regiments described in the dependent claims.
Claims 38-40: Takanobu describes different possible embodiments of the wound as being “refractory” (Takanobu, pg 4 and 10), “chronic” (Takanobu, pg 11) and a diabetic ulcer (Takanobu, pg 11).
Claims 44-48: Takanobu describes possible administration routes including topical (Takanobu, pg 8) and injection (Takanobu, pg 8 and 11). Takanobu describes this as a therapeutic treatment for mammals such as humans (Takanobu, pg 5).
Claim 41: Takanobu describes the isolation and use of M1 and M2 monocytes derived from donors (allogenic) and patients (autologous) (Takanobu, pg 5 and 4, respectively).
Claims 33-35, 41 and 49: Wang describes the isolation and activation of macrophages to M1 and M2 phenotypes using IL-4 and IL-13, respectively (Wang, abstract). Wang describes the infusion of severe combined immunodeficient (SCID) mice with either ex vivo programmed M1 or M2 macrophages as a treatment for chronic inflammatory renal disease and kidney repair (Wang, discussion para 1 and Fig 2). Wang found that M1 macrophages promoted both histological damage and functional impairment whereas M2 macrophages strongly protected renal structure and function (Wang, discussion para 1). Wang states that both M1 and M2 macrophages maintained their respective properties in vitro for up to 4 weeks (Wang, discussion para 1). Similarly, Wang does not describe the sequential administration of exogenous M1 and M2 macrophages separated by a period of at least 1 day and not more than 2 days as described in claim 33.
Claims 33-35, 37, 41 and 49: Vunjak describes the sequential promotion of endogenous M1 and M2 macrophage phenotypes as an effective means to increase tissue vascularization of an implanted scaffold (Vunjak, pg 13 and example 5 pg 68). Vunjak describes that exposure to only M1 cytokines has been shown to cause inflammation and exposure to only M2 cytokines (including subsets M2a and M2c) has been shown to causes fibrous encapsulation and promote angiogenesis (Vunjak, para 1, pg 13). Vunjak describes how the sequential exposure of M1 macrophages followed by M2 macrophages can result in improved vascularization (Vunjak, para 1 and 4, pg 13). Vunjak describes this as a therapeutic solution for tissue damage or wounds (Vunjak, para 2, pg 51). Vunjak describes administering the compounds daily, weekly, bi-weekly or monthly depending on the course of treatment (Vunjak, para 2, pg 52). Furthermore, example 8 of Vunjak’s disclosure characterizes the macrophage phenotype transition over the course of 1 to 6 days, wherein different M1 and M2 combinations were investigated (Vunjak, pg 72-75). Notably, this study is inclusive of 1-2 days, thus meeting the limitations of claim 33. Furthermore, it is argued that one of ordinary skill in the art would consider the specific timing between M1 and M2 macrophage administrations to result from routine optimization. Vunjak’s disclosure provides motivation to optimize the timing between M1 and M2 administration to improve angiogenesis, inflammation and overall wound healing, demonstrating that this is a known result-effective variable, see MPEP § 2144.05. Vunjak describes administration routes including both topical and via injection (Vunjak, pg 53 and pg 41, respectively).
Claims 36 and 43-44: Vunjak describes further embodiments wherein M1 response is followed by M2a, M2c or combinations thereof (Vunjak, para 4, pg 17). This is described in detail in examples 2-5 of the disclosure (Vunjak, pg 58-70). Vunjak describes administering the compounds daily, weekly, bi-weekly or monthly depending on the course of treatment (Vunjak, para 2, pg 52).
It would have been prima facie obvious to one of ordinary skill in the art to combine the treatment methods outlined by Takanobu and Wang using exogenous M1 and M2 macrophages with the sequential administration regiment outlined by Vunjak. Vunjak’s disclosure makes it clear than sequential wound exposure to M1 followed by M2 macrophages results in synergistic inflammatory and angiogenic properties that facilitate wound healing. Furthermore, Vunjak’s disclosure describe all combinations covered in the instant claims involving M1, M2, M2a and M2c administration and time periods thereof. One skilled in the art would immediately recognize the synergistic benefits of using a sequential administration regiment from Vunjak’s disclosure and would find it prima facie obvious to apply it to the treatment method outlined by Takanobu and Wang. One would have motivation to do so in order to improve angiogenesis, inflammation and overall wound healing. Furthermore, all the cited prior art are in the same field of endeavor, are all focused on using M1/M2 macrophages for wound healing, and all describe both topical and injection administration routes and would therefore have a reasonable expectation of success.
With respect to administering the M2 macrophage at least 1 day and not more than 2 days following the administration of the M1 macrophage, it would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine this optimal range. "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
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