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 should note that the examiner assigned to this case has changed.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 9/15/2025 has been entered.
Response to Amendments
Applicant's amendments filed 9/15/2025 to claims 1 and 2 have been entered. Claims 1-22 remain pending, and are being considered on their merits. No claims are withdrawn at this time. References not included with this Office action can be found in a prior action.
In view of the decision by the Patent Trial and Appeal Board dated 7/22/2025 the following rejections are withdrawn: 1) the 35 U.S.C. § 103 rejection of claims 20 and 21 over Werber in view of Lyons, 2) The 35 U.S.C. § 103 rejection of claims 8, 9, 16, 18, 19, and 22 over Werber in view of Lyons and Koob, 3) the 35 U.S.C. § 103 rejection of claims 10-12 over Werber in view of Lyons, Koob, and Samaniego, 4) the 35 U.S.C. § 103 rejection of claim 13 over Werber in view of Koob, and ThermoScientific, and 5) the 35 U.S.C. § 103 rejection of claims 14, 15, and 17 over Werber in view of Lyons, Koob, Samaniego, and Werber2. New grounds of rejection are set forth below.
Any other rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 14945128, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The disclosure of the prior application provides general discussion of evaporation of plasma that has been combined with a placental membrane, and provides support for claims 1, 6 and 8. The disclosure of the prior application does not provide any support for the limitations of making the product with dehydration recited in claims 2-5, 7 and 9-20. Therefore claims 2-5, 7 and 9-20 are given the effective filing date of 05/09/2018.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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 2-6 are 10-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 2 recites “wherein partially dehydrating fluid from the plasma removes at least 1% of fluid from the plasma”. Similarly, claim 10 has been amended to recite “wherein partially dehydrating fluid from the composition removes at least 1% of fluid from the amniotic fluid”. The range of “at least 1%” does not recite an end point and thus contemplates all end points above 1%. The specification does not provide support for such a range wherein the end point is any end point above 1%. Paragraph [0099] of the as filed specification is the only paragraph that recites ranges for the amount of fluid removed. This paragraph only recites the ranges 1% to 95%, 10% to 80%, and 50% to 70%. Therefore end points such as anything above 95%, which are specifically included in the claimed “at least 1%”, lack any support. Therefore claims 2 and 10 are rejected for including new matter.
Since claims 3-6 and 11-13 depend from claims 2 and 10, and because said claims do not further limit to claims to any ranges which contain support in the specification, they too are rejected for including new matter.
Claims 1-7, 11, and 20-22 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “substantially” in claims 1, 20, and 22, is a relative term which renders the claims indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree (such as but not limited to a controlling definition), and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Correction is required.
Claim 3 recites “wherein partially dehydrating fluid from the composition comprises centrifuging the composition and removing a bulk of supernatant therefrom, said supernatant being used to generate the concentrated fluid.” There is insufficient antecedent basis for the limitation “the composition” that the fluid is being dehydrated from in order to “generate the concentrated fluid”. Independent claim 1 recites only one composition, a composition that that is a combination of “the concentrated fluid” and “an extracellular matrix of biological membrane”. Therefore the only “composition” in claim 1 already contains “the concentrated fluid”, and there is insufficient antecedent basis for any “composition” that the fluid is being dehydrated from in order to “generate the concentrated fluid”. Importantly, independent claim 1 recites that “plasma” is being dehydrated in the dehydration step, not a “fluid” or a “composition”. It is unclear if claim 3 is attempting to further limit the dehydration step in independent claim 1 or if it is attempting to add an additional dehydration step. Therefore, the metes and bounds are unclear.
Claim 11 recites “wherein partially dehydrating fluid from the composition comprises centrifuging the composition and removing a bulk of supernatant therefrom, said supernatant being used to generate the concentrated fluid.” There is insufficient antecedent basis for the limitation “the composition” that the fluid is being dehydrated from in order to “generate the concentrated fluid”. Independent claim 8 recites only one composition, a composition that that is a combination of “the concentrated fluid” and “the intact portions of intermediate layer”. Therefore the only “composition” in claim 8 already contains “the concentrated fluid”, and there is insufficient antecedent basis for any “composition” that the fluid is being dehydrated from in order to “generate the concentrated fluid”. Additionally, it is unclear if this dehydration step in claim 11 is a secondary dehydration step to the dehydration step in independent claim 8 or if this limitation is referring to the dehydration step claimed dehydration step in independent claim 8. Claim 10 recites dehydrating “from the fluid” and independent claim 8 requires dehydrating “amniotic fluid” specifically. Thus, it is unclear if the fluid recited in claim 10 is different from claim 8. Therefore, the metes and bounds are unclear.
In so much that claims 2-7 and 21 depend from either claim 1 and 20 and do not resolve the point of confusion, these dependent claims must be rejected with claims 1 and 20 as indefinite.
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 1, 5, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over of Werber et al. (US Patent 9,132,156; of record in IDS filed 11/5/2018).
Regarding claims 1, 6 and 20, Werber teaches a therapeutic composition comprising: a harvested acellular amniotic membrane comprising intermediate layer and a carrier fluid that is an acellular amniotic fluid, and wherein the therapeutic composition is essentially free of any viable amniotic membrane cells or viable amniotic fluid cells, wherein the membrane is dispersed in the fluid comprising the amniotic fluid (see claim 1; column 11, lines 2-4; figure 1 and 4) and which is not formulated as particles (Figure 11 and Col. 11, lines 46-54); Werber’s teaching of using the composition for therapeutic purposes reads on “presenting”. Regarding claims 1 and 20-21, Werber teaches the amniotic fluid can be treated by centrifugation, filtration, or other process to remove essentially all of the cells and/or cell debris (see column 14, lines 36-43); this teaching together with Werber not teaching the inclusion of amnion or chorion membrane particles in the fluid reads on “said plasma containing substantially no amnion or chorion membrane particles” and the active step of removing remnants of placental cells in claims 20-21. Regarding claims 1 and 20, Werber teaches the amniotic fluid may be heated or allowed to evaporate, with or without vacuum, to concentrate the amniotic fluid (see column 11 lines 7-15); reads on partially dehydrating fluid from the composition to generate an impregnated biological membrane. Regarding claims 1 and 20, Werber teaches growth factors are concentrated in a therapeutic composition, whereby the concentration is higher than in the received donor tissue or fluid (see column 1 lines 45-50). Regarding the limitation of “intact portions”, Werber’s micronized particles of membrane read on “intact portions” of membrane. Regarding claim 5, Werber teaches additional materials including diluents or a second therapeutic composition may be included with the amnion derived therapeutic composition (see column 1 lines 50-53).
Regarding claim 1, Werber does not exemplify evaporating the amniotic fluid prior to the combining step, or from the combination of amniotic membrane and amniotic fluid. Werber does not exemplify adding additional plasma (amniotic fluid) to the composition. However, it would have been obvious to concentrate the amniotic fluid by evaporation before or after the step of combining with the membrane. A person of ordinary skill in the art would have had a reasonable expectation of success in concentrating the amniotic fluid by evaporation before or after the step of combining with the membrane because Werber teaches that evaporation concentrates factors in the fluid and Werber does not teach that the evaporation must be done in any order. The skilled artisan would have been motivated to concentrate the amniotic fluid by evaporation before or after the step of combining with the membrane because Werber teaches that evaporation is useful to concentrate the amniotic fluid.
Similarly, it would have been obvious to add additional amniotic fluid to Werber’s composition. A person of ordinary skill in the art would have had a reasonable expectation of success in adding additional amniotic fluid to the composition because Werber teaches that diluents can be added and Werber establishes it is useful to add amniotic fluid. The skilled artisan would have been motivated to add additional amniotic fluid to Werber’s composition because Werber teaches that amniotic fluid is useful in the composition.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claims 2-4 are rejected under 35 U.S.C. 103 as being unpatentable over Werber as applied to claim 1 above, and further in view of Samaniego et al. (US 2015/0157761).
The teachings of Werber are discussed and relied upon above. Additionally, regarding claim 3, Werber teaches that the amniotic fluid may first be processed by centrifugation to remove cells prior to the concentrating steps (see col. 2 lines 33-40).
Werber does not teach the level of evaporation (claim 2) or evaporation via heating (claim 4).
Samaniego teaches a method of preparing tissue for therapeutic purposes comprising combining the tissue with a solution, and evaporating the solution (see abstract). Samaniego teaches the tissue may be amniotic tissue (see paragraph [0028]). Samaniego teaches final moisture content of the tissue following evaporation may be less than 10%, and that the evaporation method involves heating in a heating chamber (see paragraphs [0008] and [0060]).
It would have been obvious to combine Werber and Samaniego to evaporate the fluid in Werber’s composition to a level of about 10% using a heating chamber. A person of ordinary skill in the art would have had a reasonable expectation of success in evaporating the fluid in Werber’s composition to a level of about 10% using a heating chamber because Samaniego establishes this is a suitable evaporation method. The skilled artisan would have been motivated to evaporate the fluid in Werber’s composition to a level of about 10% using a heating chamber because Samaniego teaches this is a useful evaporation method for preparation of products for therapeutic uses.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Werber as applied to claim 1 above, and further in view of Daniel et al. (U.S. PGPUB 20100104539).
Werber does not teach the amniotic membrane is not morselized.
Regarding claim 7, like Werber, Daniel also is drawn to a therapeutic composition comprising a placental tissue component (see paragraph abstract). Regarding claim 7, Daniel teaches that the therapeutic composition comprising a placental tissue component can be made without morselizing the tissue (see paragraph [0051]-[0053]).
It would have been obvious to combine Werber and Daniel to use Daniel’s non- morselized membrane in Weber’s therapeutic composition. A person of ordinary skill in the art would have had a reasonable expectation of success in using Daniel’s non- morselized membrane in Weber’s therapeutic composition Daniel teaches that the therapeutic composition comprising a placental tissue component can be made without morselizing the tissue. The skilled artisan would have been to use Daniel’s non- morselized membrane in Weber’s therapeutic composition because Daniel specifically teaches that non-morselized tissue is useful in the therapeutic compositions.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 8, 10-12, 16, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over of Werber et al. (WO 2015/134936; Reference N, and hereafter referred to as “Werber3”) in view Samaniego et al. (US 2015/0157761).
Regarding claims 8 and 20, Werber3 beneficially teaches a therapeutic composition and methods of making thereof comprising: acellular amniotic membrane; a carrier fluid, wherein the carrier comprises an acellular amniotic fluid (reads on “preservation media derived from” plasma), wherein the acellular amniotic membrane fraction is combined with the amniotic fluid (see paragraphs [0004] and [0094], and claims l, 8-9 and 13-15), and wherein the amnion layer comprising an intact intermediate layer is separated from the chorion (Fig. 1B, ¶0012, and ¶0070). Regarding claims 8 and 20, Werber3 teaches an embodiment wherein the therapeutic composition that fluid components are imbibed into a matrix component, wherein the matrix component may be in the form of a sheet (see paragraph [0012]) reads on an “intact biological scaffold”. Regarding claim 19, Werber3 does not teach that the composition is irradiated. Regarding claim 20, Werber3 teaches an acellular amniotic fluid (claim 8) and centrifuging said amniotic fluid (¶0079 and Fig. 8), reading on the removing step of claim 20 and the centrifugation of claim 21.
Regarding claim 8, Werber3 does not teach partially dehydrating the amniotic fluid. Regarding claims 8 and 16, Werber3 does not exemplify adding additional plasma (amniotic fluid) to the composition. Regarding claim 8, Werber3 does not teach dehydrating the amniotic fluid.
Samaniego teaches a method of preparing tissue for therapeutic purposes comprising combining the tissue with a solution, and evaporating the solution (see abstract). Samaniego teaches the tissue may be amniotic tissue (see paragraph [0028]). Samaniego teaches final moisture content of the tissue following evaporation may be less than 10%, and that the evaporation method involves heating in a heating chamber (see paragraphs [0008] and [0060]), reading on the dehydrating of claims 8 and 10-12.
Regarding claims 8 and 10-12, it would have been obvious to combine Werber3 and Samaniego to evaporate the fluid in Werber3’s composition to a level of about 10% using a heating chamber. A person of ordinary skill in the art would have had a reasonable expectation of success in evaporating the fluid in Werber3’s composition to a level of about 10% using a heating chamber because Samaniego establishes this is a suitable evaporation method. The skilled artisan would have been motivated to evaporate the fluid in Werber3’s composition to a level of about 10% using a heating chamber because Samaniego teaches this is a useful evaporation method for amniotic tissue for therapeutic uses.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Werber3 and Samaniego as applied to claim 8 above, and further in view of Brown et al. (US 2014/0140964; Reference A).
The teachings of Werber3 are relied upon as set forth above.
Regarding claim 9, Werber3 does not teach collecting the intermediate layer from at least one newly exposed surface of the amniotic membrane or chorion membrane.
Brown teaches methods of obtaining modified placental tissue and administering said modified placental tissue to subjects to elicit stem cell recruitment in vivo (¶0007-0010), reading on claim 9. Brown teaches that the modified placental tissue refers to segmented/isolated components of the placental tissue such as the intermediate layer (¶0030), reading on claim 9.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to further separate the intermediate layer from the amniotic membrane of Werber3 in view of Brown. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Brown and Werber3 are in-part directed towards amniotic membrane compositions and methods of obtaining thereof. The skilled artisan would have been motivated to do so because Brown teaches that modified placental tissue such as the intermediate layer is advantageous to elicit stem cell recruitment in vivo in subjects, and so would predictably improve upon Werber3’s intact amniotic membrane composition and methods of making thereof.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Werber3 and Samaniego as applied to claims 8 and 10-12 above, and further in view of Thermo Scientific (2016, Revolutionary solvent evaporation complete laboratory workflow).
The teachings of Werber3 and Samaniego are relied upon above. Samaniego further teaches that for evaporation, it is useful to use a temperature of below about 40 degrees Celsius (see paragraph [0008]).
Werber3 does not teach evaporation using a centrifuge and removing the supernatant.
Thermo Scientific teaches centrifuges that remove the supernatant can be used for evaporation that are useful for preparing evaporated samples (see entire pamphlet). Thermo Scientific teaches evaporation centrifuges include a temperature control, and that depending on the sample, different evaporation times can be between 30 minutes and 6 hours (see pages 2 and 7). Thermo Scientific teaches software controlling the evaporation process can be optimized for each customer application and new methods created to enhance performance (see page 4).
It would have been obvious to combine Werber3 and Thermo Scientific to evaporate the fluid in Werber3’s composition using centrifugation. A person of ordinary skill in the art would have had a reasonable expectation of success in evaporating the fluid in Werber3’s composition using centrifugation because Thermo Scientific establishes this is a suitable evaporation method. The skilled artisan would have been motivated to evaporate the fluid in Werber3’s composition using centrifugation because Thermo Scientific teaches this is a useful evaporation method.
Regarding the limitation wherein the centrifugal is operated at 200-1000 times gravity, the speed at which the centrifuge is used is result effective as higher speeds will concentrate the sample to a greater degree in less time. Additionally, Thermo Scientific teaches software controlling the evaporation process can be optimized.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claims 14, 15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Werber3 and Samaniego as applied to claim 8 above, and further in view of Werber et al. (WO 2015/134936; of record in IDS filed 10/18/2021; herein after “Werber2”).
The teachings of Werber3 and Samaniego are discussed and relied upon above. Werber3 further teaches an example wherein 8 square centimeters of amniotic membrane was used to make the product (see paragraph [0094]), reading in-part on claims 1, 15, and 17. Werber3 further teaches the therapeutic composition in a fluid component may be provided in any effective amount from about 1 mg/mL to more than about 500 mg/mL (see paragraph [0009])., reading in-part on claims 14, 15, and 17.
Regarding claims 14, 15, and 17, Werber3 does not teach the claimed ratios or concentrations of amniotic fluid added to the amniotic membrane comprising intermediate layer
Werber2, like Werber3, teaches a therapeutic composition comprising: acellular amniotic membrane particles; a carrier fluid, wherein the carrier comprises an acellular amniotic fluid, and wherein the therapeutic composition is essentially free of any viable amniotic membrane cells or viable amniotic fluid cells, and wherein the acellular amniotic membrane fraction is combined with the amniotic fluid (see claims 1, 8-9 and 13-15). Regarding claims 14-15 and 17, Werber2 teaches adjusting the amount of amniotic membrane needed to obtain a concentration of 1cm2/mL of therapeutic solution (see paragraph [0103]); while Werber2 does not teach the weight of 1cm2 of tissue, it appears that this 1:1 ratio is within the claimed range, or is an obvious variant of the claimed range.
Regarding claims 14, 15, and 17, It would have been obvious to combine Werber3 and Werber2 to use the concentration of amniotic fluid taught by Werber2 in Werber3’s method. A person of ordinary skill in the art would have had a reasonable expectation of success in using the concentration of amniotic fluid taught by Werber2 in Werber3’s method because Werber2 exemplifies that this is a useful amount. The skilled artisan would have been motivated to use the concentration of amniotic fluid taught by Werber2 in Werber3’s method because Werber is silent as to the amount of amniotic fluid that should be added and Werber2 provides guidance on this step.
It would have been obvious to combine Werber3 and Werber2 to add the same amount of amniotic fluid to the composition after the dehydration step. A person of ordinary skill in the art would have had a reasonable expectation of success in adding the same amount of amniotic fluid to the composition after the dehydration step because Werber2 exemplifies that this is a useful amount to have in the composition. The skilled artisan would have been motivated to add the same amount of amniotic fluid to the composition after the dehydration step because while Werber teaches the benefits of dehydrating the amniotic fluid, both Werber and Werber2 teach that it is also useful to have amniotic fluid in the final product.
It would be obvious to adjust the ratio of the plasma portion to membrane portion within the product based upon the beneficial teachings provided by Werber2 –including because such adjustments are deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claims 1-12, and 14-22 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad et al. (Clinical and Experimental Dermatology (2013), 38, 646-651; Reference U) in view of Thakoersing et al. (Tissue Engineering: Part A (2010), 16(4), 1433-1441; Reference V).
Mahmoudi-Rad teaches an intact acellular human amniotic membrane, obtained from mothers who had given birth at full term via caesarean section and decellularized by a combination of freeze-thawing and mechanical scraping reading in-part on claims 1, 5, 8, 16, and 20. Mahmoudi-Rad teaches seeding fibroblasts on the acellular human amniotic membrane to generate a skin substitute (pages 647-648, subheading “Preparation of skin substitute”), reading in-part on claims 1, 5, 8, 16, and 20. Mahmoudi-Rad teaches human plasma, as a known scaffold for fibroblasts and keratinocytes in skin substitute compositions (the paragraph spanning pages 648-649), reading in-part on claims 1, 5, 8, and 20.
Regarding claims 1, 8, and 20, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising plasma. Regarding claims 14, 15, and 17, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising plasma at the claimed concentration ranges. Regarding claims 6 and 18, Mahmoudi-Rad does not teach amniotic fluid. Regarding claim 21, Mahmoudi-Rad does not teach a centrifugation of amniotic fluid to remove placental cells.
Thakoersing teaches generating dermal equivalent compositions by culturing fibroblasts and keratinocytes on collagen gels under submerged conditions and further adding 200 μL amniotic fluid (page 1434, paragraph starting “Generated on dermal equivalents…” through paragraph ending “…as the collagen HSEs.”), reading on the embodiment of amniotic fluid for claims 1, 6, 8, 18, 20, and 21 and reading in-part on the plasma concentrations of claims 14, 15, and 17. Thakoersing teaches adding 0.5-1.0 x 106 cells per collagen gel (page 1434), reading in-part on the plasma concentrations of claims 14, 15, and 17. Thakoersing teaches that the amniotic fluid-treated human skin equivalents (AF) have a similar morphology to human skin equivalents cultured on collagen and submerged (SM) and cultured on collagen and air-exposed (AE) and contain all epidermal cell layers and resemble the morphology of human skin (Figure 1, the bottom row as compared to “Collagen SM” and Collagen AE”; page 1435, paragraph starting “To determine whether all the epidermal layers…” through the paragraph spanning pages 1435-1436), reading on claims 1, 8, and 20, and reading in-part on the plasma concentrations of claims 14, 15, and 17. Thakoersing teaches centrifuging the amniotic fluid to obtain a cell free solution (the paragraph spanning both columns on page 1434), reading on claims 20 and 21.
Regarding the embodiment of the centrifuged human amniotic fluid of claims 1, 6, 8, 18, 20, and 21, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See M.P.E.P. § 2144.06. In this case, the human amniotic membrane of Mahmoudi-Rad and the human amnionic plasma of Thakoersing are taught as useful for the same purpose as starting reagents to generate human skin equivalent compositions, and so their combination must be held prima facie obvious absent any persuasive showing of nonobviousness to the contrary.
Regarding the plasma concentrations of claims 14, 15, and 17, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, Thakoersing makes clear that the plasma concentration is necessarily result-effective to generating human skin equivalent compositions having similar morphology to human skin. Thus, the burden is shifted back to establish criticality of the claimed plasma concentration range by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad, Samaniego and Thakoersing as applied to claims 8, 10, and 12 above, and further in view of Thermo Scientific (2016, Revolutionary solvent evaporation complete laboratory workflow).
The teachings of Mahmoudi-Rad, Samaniego and Thakoersing are relied upon above. Samaniego further teaches that for evaporation, it is useful to use a temperature of below about 40 degrees Celsius (see paragraph [0008]).
Mahmoudi-Rad, Samaniego and Thakoersing does not teach evaporation using a centrifuge and removing the supernatant.
Thermo Scientific teaches centrifuges that remove the supernatant can be used for evaporation that are useful for preparing evaporated samples (see entire pamphlet). Thermo Scientific teaches evaporation centrifuges include a temperature control, and that depending on the sample, different evaporation times can be between 30 minutes and 6 hours (see pages 2 and 7). Thermo Scientific teaches software controlling the evaporation process can be optimized for each customer application and new methods created to enhance performance (see page 4).
It would have been obvious to further evaporate the plasma fluid in Thakoersing’s amniotic fluid composition using centrifugation in view of Thermoscientific and Samaniego. A person of ordinary skill in the art would have had a reasonable expectation of success in evaporating the fluid in Thakoersing’s amniotic composition using centrifugation because Thermo Scientific establishes this is a suitable evaporation method. The skilled artisan would have been motivated to evaporate the fluid in Werber3’s composition using centrifugation because Thermo Scientific teaches this is a useful evaporation method.
Regarding the limitation wherein the centrifugal is operated at 200-1000 times gravity, the speed at which the centrifuge is used is result effective as higher speeds will concentrate the sample to a greater degree in less time. Additionally, Thermo Scientific teaches software controlling the evaporation process can be optimized.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Response to Arguments
Applicant's arguments on pages 5-7 of the reply have been fully considered, but not found persuasive of error. Werber clearly teaches a harvested acellular amniotic membrane comprising intermediate layer and a carrier fluid that is an acellular amniotic fluid, and wherein the therapeutic composition is essentially free of any viable amniotic membrane cells or viable amniotic fluid cells, wherein the membrane is dispersed in the fluid comprising the amniotic fluid (see claim 1; column 11, lines 2-4; figure 1 and 4), and so meeting the broadest reasonable interpretation of the scope of claim 1.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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