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 the Claims
Claims 1-17 and 22-25 are pending (claim set as filed on 07/28/2025).
Priority
This application is a CON of 15/309,566 (now abandoned) which is a 371 of PCT/US2015/030717 filed on 05/14/2015, which has provisional applications to: 62/006,986 filed on 06/03/2014 and 61/993,089 filed on 05/14/2014.
Withdrawal of Rejections
The response and amendments filed on 07/28/2025 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s response to arguments section.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New Grounds of Rejection Necessitated by Amendment
Claim Rejections - 35 USC §103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8, 10-14, 16, and 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Skardal (WO 2014/040026 A1 - cited in the IDS filed on 07/19/2023) in view of Yang (Effect of Amniotic Fluid Stem Cells and Amniotic Fluid Cells on the Wound Healing Process in a White Rat Model, 2013 - cited in the IDS filed on 07/19/2023) as evidenced by Niknejad (Properties of the Amniotic Membrane for Potential Use in Tissue Engineering - cited in the IDS filed on 07/19/2023) and Cobey (US Patent no. 3,223,083 - newly cited).
Skardal’s general disclosure relates to compositions and methods for wound healing and tissue regeneration (see abstract).
Skardal teaches a composition for inducing wound healing and tissue regeneration, where the composition comprises amniotic membrane (see page 2: Summary of the Invention). Skardal further teaches “a method for making a composition comprising amniotic membrane. The method comprises isolating an amniotic membrane from a mammal; washing the amniotic membrane; lyophilizing the amniotic membrane; and grinding the amniotic membrane to form a powder. In one embodiment, the method further comprises forming a mixture of amniotic membrane powder, pepsin, and a solution; centrifuging the mixture to form a supernatant and a pellet; and removing the supernatant, thereby forming solubilized amniotic membrane (SAM)” (see page 3, lines 18-25). Skardal teaches the composition is absorbed onto a porous collagen matrix sheet to produce a second preparation useful to promote wound healing such as skin wound (see abstract & page 3, lines 7-17, & page 23, lines 14-20, & page 24, lines 10-26, & page 44, lines 16-28, & page 41, lines 28-31).
Regarding the glycosaminoglycan, Skardal teaches the matrix can further comprise glycosaminoglycan (GAG) (see page 23, lines 21-29).
Regarding claims 3-4 and limitations pertaining to ECM structure, Skardal teaches “extracellular matrix composition includes both soluble and non-soluble fractions or any portion thereof. The non-soluble fraction includes those secreted ECM proteins and biological components that are deposited on the support or scaffold. The soluble fraction includes refers to culture media in which cells have been cultured and into which the cells have secreted active agent(s) and includes those proteins and biological components not deposited on the scaffold” (see page 11, lines 3-9). Niknejad (evidentiary reference) discloses the structural layers and elements of the ECM of amniotic membrane (see Niknejad at Figure 1).
Regarding claims 5-6, Skardal teaches “the amniotic membrane powder or SAM of the invention may be combined with natural materials, synthetic materials, or both natural and synthetic materials to produce the scaffolds of the invention. Examples of combinations include, but are not limited to: blends of different types of collagen (e.g. Type I with Type II, Type I with Type III, Type II with Type III, etc.)” (see page 31). Skardal teaches the amniotic membrane-based scaffold is applied in a flowable state to a wound or treatment site (see page 42, lines 9-14). The scaffold may be in a particular shape such as hydrogel, foam mesh, sheet, patch, and sponge (see page 23, lines 19-20). Skardal teaches the SAM may be mixed with a suitable buffer such as PBS, saline, and the like (see page 18, lines 8-10) and equal ratio of saline to protein (see page 50, lines 20-25).
Regarding claim 10, Skardal teaches the amniotic membrane is separated from the chorion membrane (see page 16, lines 8-15, & page 6, lines 13-14).
Regarding claim 11, Skardal teaches a method of inducing wound healing and tissue regeneration in a subject comprising administering a composition comprising amniotic membrane to a treatment site in the subject (see page 3, lines 27-29, & page 4, lines 23-24).
Regarding claims 12-13, 16, and claim 22 in part pertaining to an effective amount, Skardal teaches an effective amount or therapeutically effective amount of a compound is that amount of compound which is sufficient to provide a beneficial effect to the subject to which the compound is administered (see page 10, lines 26-28). Skardal teaches the scaffold may be secured to the wound area using sutures, adhesives, or overlaying bandages. The scaffold may be cut to match the size of the wound, or may overlap the wound edges (see page 42, lines 1-8). The MPEP 2144.05(II)(A) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. 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”. Thus, it is considered to be within the purview of the ordinary artisan to determine the therapeutically effective amount of the active amnion ingredient and/or changes in size or proportion based upon various patient factors such as wound size and severity (MPEP 2144.04(IV)(A)).
However, Skardal does not teach: the first preparation including amniotic fluid cells (base claims first limitation); or a first and second syringe (amended limitation of claim 1 and claim 23).
Yang teaches that amniotic fluid derived stem cells and amniocytes have been determined to have wound healing effects (see abstract). Amniotic fluid stem cells (AFSCs) are pluripotent and able to differentiate into various kinds of tissue (see page 496, right col.). Yang teaches that stem cell seeding in the collagen matrix showed much better neovascularization (see page 503, right col.).
Cobey’s general disclosure relates to a method for adhesively securing damage living tissue comprising bone, cartilage, tendon and soft tissue (claims 7-8) (see col. 1, lines 10-14). Cobey teaches two compositions are maintained separate until they are mixed in situ (see col. 4, lines 46-48) and further teaches two syringes or graduated cylinders (each comprising a composition) connected by a polyvinyl Y-tube (i.e., fluidly connected) (see col. 5, lines 6-27, and Figure 1).
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Claim interpretation: note that the claims, as a whole, are drawn to a treatment methodology of a wound because “a claim preamble has the import that the claim as a whole suggests for it” (MPEP 2111.02: Effect of the Preamble). However, the claims also incorporate limitations (e.g., claim 1 in part, claim 14 in part, claim 23, and claim 25) directed to processes of preparing or making the wound preparation/composition. In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious (MPEP 2141.02(I)). Thus, the emphasis of analysis is based upon the treatment of the wound and not per se how to make the preparation.
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ or use amnion fluid cells such as taught by Yang in the method of Skardal. The ordinary artisan would have been motivated to do so because Yang teaches that amniotic fluid cells have wound healing promoting effects. The ordinary artisan would have had a reasonable expectation of success because both references are drawn to amnion preparations for skin wound tissue repair.
Furthermore, it would have been secondly obvious to employ the double syringe apparatus of Cobey for the method of Skardal-Yang. The MPEP 2141(III) provides examples of rationales that may support a conclusion of obviousness include: (a) combining prior art elements according to known methods to yield predictable results; or (b) simple substitution of one known element for another to obtain predictable results. Thus, the double syringe apparatus of Cobey allows for compositions to be in a separate state until the time of reconstitution and application, otherwise undesired premature reactions of the compositions may occur if they were not maintained in a separate state.
Regarding claim 2 and the limitations pertaining to the administration time, although the reference is silent regarding “no more than about ten [or 180 minutes] prior to applying the second preparation to the wound”, this feature would have been readily obvious to an ordinary artisan because the immediate application of the drug or medicine after preparation (i.e., reconstitution such as mixing) would have been readily envisaged. One would have been motivated to do so is because delayed or prolong application time, for example, may result in oxidation or deterioration of the drug and/or where a patient may require immediate cessation of bleeding.
Claims 9, 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Skardal in view of Yang and Cobey as applied to claims 1-8, 10-14, 16, and 22-25 above, and in further view of Koob (US 2014/0052274 A1 - cited in the IDS filed on 07/19/2023).
The combined disclosures of Skardal, Yang, and Cobey is discussed above as it pertains to a method of providing a preparation for the treatment of a wound.
However, modified-Skardal-Yang-Cobey does not teach: the first preparation adsorbs to the sheet in an amount of about 800 µl or 300-999 µl per square inch of the sheet (claim 15); or wherein the ground amnion tissue has an average particle size in a range of about 10-1000 micrometers (claims 9 and 17).
Koob teaches the preparation of micronized placental tissue (see ¶ [0078]). In particular, Koob teaches “the particle size of the materials in the micronized composition can vary as well depending upon the application of the micronized composition. In one aspect, the micronized composition has particles that are less than 500 μm ... In one aspect, the micronized composition has particles that have a diameter less than 150 μm, less than 100 μm, or less than 50 μm. In certain aspects, particles having a larger diameter (e.g., 150 μm to 350 μm) are desirable. In all cases, the diameter of the particle is measured along its longest axis” (see ¶ [0078]-[0084]).
It would have been obvious to one of ordinary skill in the art to formulate the amnion preparation to have the claimed amount per square inch of the sheet and/or a particle size range of 10-1000 micrometers following the guidance of the cited references. The ordinary artisan would have been motivated to do so is because the primary reference of Skardal first discloses that “the range of 1 million to 700 50 million cells are suspended in medium and applied to each square centimeter of a surface of a scaffold … However, it will be appreciated that the density of cells seeded onto the scaffold may be varied. For example, greater cell densities promote greater tissue regeneration by the seeded cells, while lesser densities may permit relatively greater regeneration of tissue by cells infiltrating the graft from the host” (see Skardal at page 38, lines 20-29). Moreover, Koob discloses that “particles having a range of sizes and volumes are preferred as such particles will impart differential release rates into the wound” (see Koob at ¶ [0080]). Thus, one of ordinary skill in the art would recognize the claimed parameters are result effective variables dependent on the wound and desired tissue regenerating effects. This is motivation for someone of ordinary skill in the art to practice or test the parameter values widely to find those that are functional or optimal which then would be inclusive or cover those values as instantly claimed. Absent any teaching of criticality by the Applicant concerning the amount and particle size, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable which can be met as a matter of routine optimization (MPEP 2144.05 II).
Conclusion
No claims were 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 date of this final action.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGHI V NGUYEN whose telephone number is (571)270-3055. The examiner can normally be reached Mon-Fri: 9 - 3 pm (EST).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653