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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114.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 4/06/2026 has been entered.
Response to Amendments
Applicant's amendments filed 4/06/2026 to claim 1 have been entered. Claims 1-20 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 No claims are withdrawn at this time.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. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.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.
Regarding claim 1, the disclosure of the prior application fails to provide support for a product comprising “a preservation media derived from condensed plasma”. There is no mention of “a preservation media” in the disclosure of the prior application.
Regarding claim 1, the disclosure of the prior application also fails to provide support for a product comprising “an intact biological scaffold derived from intermediate layer of human placenta…being stored in said preservation media”. There is no mention of “an intact biological scaffold derived from intermediate layer of human placenta” being stored in any type of preservation media. The prior application discusses the draw backs of using “intact” membranes, stating for example “[s]everal drawbacks of using large intact membranes are non-optimal wound coverage, adhesion, and release of factors into relevant tissues, as well as reduced production efficiency and storage stability.” See paragraphs [0002]-[0003]. The prior application does teach an intact amniotic membrane, which comprises an intermediate layer (paragraph [0069]), but this paragraph only discusses obtaining an intact membrane prior to any processing steps. While paragraph [0070] continues by stating that the intermediate layer may be used in the same manner as the intact amniotic membrane, this paragraph is referencing the intact membrane in the prior paragraph that is intact before the processing steps. Therefore the only teachings in the prior application regarding intact membranes are (1) draw backs to using intact membranes, and (2) that the membranes may be obtained as intact membranes prior to the processing steps.
Regarding claim 1, the disclosure of the prior application fails to provide support for a product that “when digested with hyaluronidase, yields undetectable amounts of hyaluronic acid” in the disclosure of the prior application. The prior application does not mention any amount of “hyaluronic acid” nor any mention of “hyaluronidase” digestion. Any negative limitation or exclusionary proviso should have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See MPEP 2173.05(i).
Therefore independent claim 1, and dependent claims 2-20 are given the effective filing date of 02/18/2020. Additionally, the disclosure of the prior application fails to provide support for the limitations of dependent claims 3, 6, 7, 10, 12-15, and 18-20 as the prior application is totally silent as to the limitations in each of these claims. Specifically, the prior application fails to provide support for:
“at least 25% of water removed” in claim 3,
“being capable of growing human cells when inoculated with said human cells under
serum-free conditions” in claim 6,
“reduced ability of growing said human cells when rinsed with water prior to inoculating with said human cells under serum-free conditions” in claim 7,
“ability to bind platelets with a high affinity” in claim 10,
“being shelf-stable for at least 6 months at room temperature” in claim 12,
“being a contiguous piece of at least 50mg” in claim 13,
“being a contiguous piece of at least 100mg” in claim 14,
“being a contiguous piece of at least 150mg” in claim 15,
“being visibly clear” in claim 18,
“being gelatinous” in claim 19, and
“being hydrophilic” in claim 20.
Therefore these limitations further necessitate the effective filing date of 02/18/2020.
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 2-5 and 10 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.
Claims 2-5 recites the limitation "said condensed plasma” and for which there is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claims 2-5 depend, was amended with the instant reply to remove any recitation of “condensed plasma” Correction is required.
The term “essentially” in claims 4 and 5 and “high” in claim 10 are relative terms which renders the claim indefinite. The terms “essentially” and “high” are not defined by the claims, 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 Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Claim 1 recites a combination of two natural products: 1) amniotic plasma (e.g. amniotic fluid), and 2) human amniotic membrane. These natural products occur naturally in vivo as taught by Malhotra (World J Transplant (2014 June 24); 4(2): 111-121; Reference U) and together as part of fetal membranes, wherein the endogenous fetal membrane comprises an outer and vascular chorion in contact with the uterine wall and an inner amniotic membrane which is avascular and comprises epithelium, basement membrane (i.e. extracellular matrix), and stroma and is in contact with the amniotic fluid (e.g. a species of plasma when read in light of claim 5) (Figure 1 and page 112, subheading “Structure of Fetal Membranes”). At this time, there is no evidence of record that the two judicial exceptions, i.e. the natural products comprising human amniotic plasma and an intact human amniotic membrane, in the claimed composition otherwise imparts any markedly difference characteristic compared to the natural product of vascular fetal membrane comprising an amniotic membrane. See M.P.E.P. § 2106.04(c)(I).
Notwithstanding the 35 U.S.C. § 112(b) rejections above, dependent claims 2-5 are only directed towards additional limitations that further separation the natural products from their environment, and without any clear indication that the claimed composition possesses any markedly different characteristic as compared to its nearest natural counterpart. Incidental change(s) that might result from isolating a product of nature is generally insufficient, by itself, to make a product of nature markedly different to its naturally occurring counterpart in the natural state; see M.P.E.P. § 2106(II) and particularly M.P.E.P. § 2106(II)(C)(2).
Dependent claims 6, 7, and 10 only recite the latent properties of the claimed composition, and so do not rise to a markedly different characteristic absent any showing that the nearest natural counterpart being substantially identical in structure cannot possess the claimed properties; see M.P.E.P. § 2112.01.
Dependent claims 8, 9, 16, and 17 only further recite inherent/latent properties of the natural products. Malhotra teaches that human amniotic membrane comprises collagen and hyaluronic acid (page 112-113, subheading “Basement membrane” and “Anti-fibrotic and anti-inflammatory properties”).
Dependent claim 11 recites a negative product-by-process limitation to exclude freezing, but in this context would not impart any markedly different characteristic as naturally occurring fetal membrane could not be reasonably construed as having ever been frozen.
Therefore for claims 1-11, 16, and 17, the judicial exceptions are not integrated into a practical application and do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because the claims are only directed towards the natural products or inherent/latent properties therein as set forth above.
Regarding claim 12, further formulating the composition comprising human amniotic membrane to be shelf stable for at least 6 months at room temperature is routine and conventional over Allen (PLoS One (2013), 8(10), e78441; Reference V). See Allen at page 9, the paragraph immediately under Table 6.
Regarding claims 13-15, further formulating the composition comprising human amniotic membrane to be a contiguous piece of at least 150 mg is routine and conventional over Werber (WO 2015/134936; of record in IDS filed 10/18/2021). Werber beneficially teaches a therapeutic composition comprising: acellular amniotic membrane; a carrier fluid, wherein the carrier comprises an acellular amniotic fluid (reads on “preservation media derived from” plasma), and wherein the therapeutic composition is essentially free of any viable amniotic membrane cells or viable amniotic fluid cells (reads on free of red blood cells), and wherein the acellular amniotic membrane fraction is combined with the amniotic fluid (see paragraphs [0004] and [0094]). Werber teaches an example wherein 8 square centimeters of amniotic membrane was used to make the product (see paragraph [0094]). Regarding claim 15, Werber 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]).
Regarding claims 18-20, further formulating the claimed composition to be visibly clear, gelatinous, and/or hydrophilic is routine and conventional over Daniel (U.S. 2019/0192734) . Regarding claim 18, Daniel teaches that intact intermediate layer inherently can be formulated to be translucent by steps of dehydration and then rehydration (see Figure 2B and ¶0241). Regarding claim 19, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently is a spongy layer (see paragraphs [0004] and [0109]); reads on gelatinous. Regarding claim 20, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently comprises hydrophilic molecules (see paragraphs [0008]).
Therefore, claims 1-20 are rejected as patent ineligible under 35 U.S.C. § 101.
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 1-2 and 4-20 are rejected under 35 U.S.C. 103 as being unpatentable over Werber et al (WO 2015/134936; of record in IDS filed 10/18/2021) in view of Werber2 et al (US 9,132,156; of record in IDS filed 6/12/20) and Koob et al (US 2014/0271728; of record in IDS filed 2/13/2022), and as evidenced by Daniel et al (US 2019/0192734) and Haserodt et al (2011, Glycobiology, 21(2): 175–183).
Regarding claims 1-2 and 4, Werber beneficially teaches a therapeutic composition comprising: acellular amniotic membrane; a carrier fluid, wherein the carrier comprises an acellular amniotic fluid (reads on “preservation media derived from” plasma), and wherein the therapeutic composition is essentially free of any viable amniotic membrane cells or viable amniotic fluid cells (reads on free of red blood cells), and 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). Regarding claim 1, Werber 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 5, Werber does not teach including fibrinogen in the plasma. Regarding claim 6, Werber teaches that the composition in the hydrated state has ability of maintaining cell viability and Werber does not teach the use of serum (see paragraph [0007]). Regarding claims 9 and 16, Werber teaches that the composition may include collagen (see paragraph [0009]). Regarding claim 11, while Werber teaches that the composition may be frozen, Werber does not teach that it must never be frozen. Regarding claim 10, Werber teaches that the composition is compatible with platelet rich plasma (see paragraph [0016]). Regarding claims 13-15, Werber teaches an example wherein 8 square centimeters of amniotic membrane was used to make the product (see paragraph [0094]). Regarding claim 15, Werber 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]).
Regarding claim 1, Werber does not teach the acellular amniotic membrane (intact biological scaffold) is derived from a human placental intermediate layer or that the acellular amniotic fluid (plasma) is concentrated (claim 1) human amniotic fluid (claim 2).
Regarding claims 1-2 and 4, like Werber, Werber2 teaches a therapeutic composition comprising: a harvested acellular amniotic membrane and a carrier fluid that is an acellular amniotic fluid (reads on plasma), 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 4). Regarding claim 1, Werber2 teaches that the composition may be made from human tissue and fluid (see col. 8 lines 29-35). Regarding claims 1 and 2, Werber2 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). Regarding claim 1, Werber2 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 claim 11, while Werber2 teaches that the composition may be frozen, Werber2 does not teach that it must ever be frozen. Regarding claims 11-12, Werber2 teaches an acellular amnion derived therapeutic composition may be able to be kept at room temperature for long periods of time (see col. 3 lines 61-64).
Regarding claim 1, like Werber and Werber2, Koob also is drawn to a therapeutic composition comprising a placental tissue component (see paragraphs [0004] and [0007]-[0008]). Regarding claim 1, Koob placental tissue is known in the art as a basis for wound coverings and wound healing, and wound covering or wound healing compositions comprising placental tissue components typically were in the form of grafts wherein individual layers (see paragraph [0004]). Regarding claim 1, Koob teaches that the composition comprises one or more placental tissues selected from the amnion, chorion, intermediate tissue layer, having a sufficient density and cohesiveness to maintain their size and shape at least until further processing, and that after processing the composition is sufficiently cohesive such that the placental tissue composition does not break, splinter, disintegrate or fragment during introduction into a subject (see paragraphs [0008] and [0010]); reads on “intact biological scaffold derived from intermediate layer”. Additionally, Koob teaches that different layers can be separated, depending on what layers are desired (see Koob for example at paragraphs [0047] and [0049]). Therefore, Koob not only teaches the different layers have a similar function in that any one or all of them can be used in therapeutic compositions, but Koob also teaches how to isolate the desired layer. Regarding claims 1, Koob teaches that the composition may have a desired defined size and shape (see paragraph [0008]). Regarding claim 1, Koob teaches that the therapeutic composition permits the attending clinician significant flexibility in treating the patient taking into account the purpose of the treatment (see paragraph [0009]). Regarding claims 1-2, Koob teaches that the therapeutic composition may be human tissue (see paragraphs [0038] and [0040]). Regarding claim 11, while Koob teaches that the composition may be frozen, Koob does not teach that it must ever be frozen. Regarding claims 9 and 16, Koob teaches that the composition may beneficially include collagen (see paragraph [0074]).
Regarding claims 1, 8-9 and 16-17, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently comprises hyaluronic acid and collagens, as well as other components (see paragraphs [0004] and [0109]). Regarding claim 19, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently is a spongy layer (see paragraphs [0004] and [0109]); reads on gelatinous. Regarding claim 18, Daniel is an inherency reference cited solely as evidence that intact intermediate layer inherently can be translucent (see Figure 2B). Regarding claim 20, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently comprises hydrophilic molecules (see paragraphs [0008]).
Regarding claim 1, Haserodt is an inherency reference cited solely as evidence that digestion of hyaluronic acid with hyaluronidase inherently breaks down the hyaluronic acid such that the low molecular weight hyaluronic acid cannot be detected (see Figure 1B). Additionally, the inherency reference Haserodt also specifically highlights that low molecular weight HA inherently cannot be detected by at least two ELISA kits (see abstract). It is noted that this is the same as the statement in paragraph [0156] of the as filed specification, which states “[t]he scaffold product digested with hyaluronidase did not yield detectable hyaluronic acid due to the low molecular weight of the fragments produced form this treatment which is below the molecular weight threshold for the ELISA used (data not shown).” Therefore, the limitation of “when digested with hyaluronidase, yields undetectable amounts of hyaluronic acid” as given the broadest reasonable interpretation consistent with the specification, is an inherent property as evidenced by Haserodt.
Regarding claim 1, It would have been obvious to combine Werber and Werber2 to use human tissue and concentrated human amniotic fluid in Werber’s human amniotic membrane composition. A person of ordinary skill in the art would have had a reasonable expectation of success in use human tissue and concentrated human amniotic fluid in Werber’s composition because Werber2’s composition comprises the same materials, amniotic tissue and fluid, and Werber2 teaches it is both useful to concentrate the beneficial factors in the amniotic fluid and to use human fluid and tissue. It is also noted that Koob also teaches it is useful to use human tissue, therefore this reference further supports this motivation. The skilled artisan would have been motivated to use human tissue and concentrated human amniotic fluid in Werber’s composition because Werber2 teaches it is both useful to concentrate the beneficial factors in the amniotic fluid and to use human fluid and tissue.
Regarding claims 13-15, it would have been obvious to combine Werber and Koob to use Koob’s intermediate layer in Weber’s therapeutic composition, such that an intact biological scaffold is derived from the intermediate layer and that it forms a contiguous piece of at least 150 mg. A person of ordinary skill in the art would have had a reasonable expectation of success in using Koob’s intermediate layer to derive an intact biological scaffold that it forms a contiguous piece of at least 150 mg in Werber’s therapeutic composition because Koob teaches said intermediate layer that is in a cohesive (intact) form is useful in therapeutic compositions. Additionally, Werber provides an example wherein amniotic membrane can be obtained in pieces of 8 centimeters squared. The skilled artisan would have been motivated to use Koob’s intermediate layer in Weber’s therapeutic composition because Koob teaches said intermediate layer is useful in therapeutic compositions. Additionally, Koob teaches that these therapeutic compositions permit the attending clinician significant flexibility in treating the patient taking into account the purpose of the treatment. Alternatively, the skilled artisan would have been motivated to use Koob’s intermediate layer to derive an intact biological scaffold in Werber’s therapeutic composition because Werber teaches that acellular amniotic material is useful in the therapeutic composition. The skilled artisan would have been motivated to use Koob’s intermediate layer portion wherein it forms a contiguous piece of at least 150 mg in Weber’s therapeutic composition because Werber and teaches the usefulness of sheets of the therapeutic composition while Koob’s intermediate layer can be made in portion that is a desired size and shape while remaining intact such that it does not break, splinter, disintegrate or fragment during introduction into a subject. Therefore there is motivation form a product with a contiguous piece of intermediate membrane that is substantially large that the weight would be more than 150 mg. Furthermore, the reference specifically teach that the size can be adapted and they do not teach any reasons for an upper limit on forming a large product that would contain more than 150 mg of intermediate membrane.
Werber in view of Werber2 and Koob are silent as to the functional properties of the product in claims 6-7, 10 and 12. However, the Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' acellular product differs, and if so to what extent, from the acellular product discussed in Werber in view of Werber2 and Koob. The prior art acellular product comprises the same structural materials as the claimed product, namely human amniotic intermediate layer and concentrated human amniotic fluid. The cited art taken as a whole demonstrates a reasonable probability that the acellular product of the prior art is either identical or sufficiently similar to the claimed acellular product that whatever differences exist are not patentably significant. For example, as stated above, Werber teaches that the composition in the hydrated state has ability of maintaining cell viability and Werber does not teach the use of serum, and that the composition is compatible with platelet rich plasma. Additionally, Werber2 teaches an acellular amnion derived therapeutic composition may be able to be kept at room temperature for long periods of time. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants.
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 3 is rejected under 35 U.S.C. 103 as being unpatentable over Werber in view of Werber2 and Koob, and as evidenced by Daniel and Haserodt, as applied to claims 1-2 and 4-20 above, and further in view of Samaniego et al (US 20150157761).
The teachings of Werber in view of Werber2 and Koob are discussed and relied upon above.
Werber does not teach the amount of water removed during the concentration of the amniotic fluid (claim 3).
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% (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%. 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% 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% because Samaniego teaches this is a useful evaporation method for preparation of products for therapeutic uses and Werber2 establishes that it is beneficial to concentrate the amniotic fluid.
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, 2, 4-10, 16, and 17 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 W) in view of Thakoersing et al. (Tissue Engineering: Part A (2010), 16(4), 1433-1441; Reference X) and as evidenced by Malhotra et al. (World J Transplant (2014 June 24); 4(2): 111-121; Reference U).
Mahmoudi-Rad teaches an intact acellular human amniotic membrane comprising collagen (e.g. the intermediate layer), obtained from mothers who had given birth at full term via caesarean section, to prevent any possible contamination during normal vaginal delivery and who tested negative for HIV, hepatitis B and C, and syphilis (page 647, subheading “Preparation of amniotic membrane” and Figure 2), reading in-part on claim 1, 8, and 16. 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 and 6. Mahmoudi-Rad teaches that type I collagen, acellular dermis, human plasma (formulated as clotted plasma-based matrix), collagen-glycosaminoglycan matrix, and fibrin glue as known scaffolds for fibroblasts and keratinocytes in skin substitute compositions (the paragraph spanning pages 648-649), reading in-part on the human amniotic plasma of claim 1.
Regarding claims 9 and 17, Mahmoudi-Rad is silent regarding the human amniotic membrane comprising hyaluronic acid. However, Malhotra teaches that human amniotic membrane inherently comprises hyaluronic acid (page 112-113, subheading “Basement membrane” and “Anti-fibrotic and anti-inflammatory properties”). Therefore, Mahmoudi-Rad as evidenced by Malhotra inherently reads on claims 9 and 17; see M.P.E.P. § 2112.
Regarding claims 1 and 2, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising human amniotic plasma. Regarding claim 4 and in view of the indefiniteness rejection above, Mahmoudi-Rad does not teach a composition lacking red blood cells. Regarding claim 5 and in view of the indefiniteness rejection above, Mahmoudi-Rad does not teach a composition lacking fibrinogen.
Thakoersing teaches generating dermal equivalent compositions by culturing fibroblasts and keratinocytes on collagen gels under submerged conditions and further adding 200 μL amniotic fluid having been centrifuged to remove cels (page 1434, paragraph starting “Generated on dermal equivalents…” through paragraph ending “…as the collagen HSEs.”), reading on claims 1, 2, and the negative limitation of claim 4. Thakoersing does not teach fibrinogen as part of the amniotic fluid-treated human skin equivalent (HSE) compositions (page 1434, paragraph starting “Generated on dermal equivalents…” through paragraph ending “…as the collagen HSEs.”), reading on the negative limitations of claim 5. 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, 2, 4, and 5.
Regarding the embodiment of human amniotic plasma of claims 1, 2, 4, and 5, "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 claims 6, 7, and 10, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See M.P.E.P. § 2111.02 and 2111.04. In this case, claims 6 and 7 only appear to recite the intended use of the claimed composition, and so the prior art teachings of Mahmoudi-Rad combined with Thakoersing is reasonably presumed to be capable of meeting the intended use of claims 6 and 7 absent any showing to the contrary.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad and Thakoersing as applied to claims 1 and 2 above, and further in view of Samaniego et al (US 2015/0157761).
The teachings of Mahmoudi-Rad and Thakoersing are relied upon as set forth above.
Regarding claim 3, Mahmoudi-Rad and Thakoersing do not teach the amount of water removed during the concentration of 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% (see paragraphs [0008] and [0060]), reading on claim 3.
It would have been obvious to combine Mahmoudi-Rad and Samaniego to evaporate the fluid in Mahmoudi-Rad’s composition to a level of about 10% in view of Thakoersing. A person of ordinary skill in the art would have had a reasonable expectation of success in evaporating the fluid in Mahmoudi-Rad’s composition to a level of about 10% in view of Thakoersing because Samaniego establishes this is a suitable evaporation method. The skilled artisan would have been motivated to evaporate the fluid in Mahmoudi-Rad’s composition to a level of about 10% in view of Thakoersing because Samaniego teaches this is a useful evaporation method for preparation of products for therapeutic uses and Werber2 establishes that it is beneficial to concentrate the amniotic fluid.
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 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad and Thakoersing as applied to claim 1 above, and further in view of Allen et al. (PLoS One (2013), 8(10), e78441; Reference V).
The teachings of Mahmoudi-Rad and Thakoersing are relied upon as set forth above. Mahmoudi-Rad further teaches freezing the intact human amniotic membrane after evaluating the donor mothers for viral and bacterial infection (page 647, subheading “Preparation of amniotic membrane”), reading in-part on claim 11.
Regarding claim 11, Mahmoudi-Rad and Thakoersing do not teach the negative product-by-process limitation to not freezing the product. Regarding claim 12, Mahmoudi-Rad and Thakoersing do not teach the product being shelf-stable for at least 6 months at room temperature.
Allen teaches a dried and intact human amniotic membrane composition (Abstract). Allen teaches the dried human amniotic membrane is not frozen as part of its methods of preparation (pages 2-3, subheading “Dried”), reading on claim 11. Allen teaches the dried human amniotic membrane to be shelf stable for at least 6 months at room temperature ( page 9, the paragraph immediately under Table 6), reading on claim 12. Allen teaches that freezing amniotic membrane has known drawbacks such as lower levels of angiogenic factors (the paragraph spanning pages 1-2), reading on claims 11 and 12.
Regarding claims 11 and 12, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further substitute the freezing step of Mahmoudi-Rad in preparing intact human amniotic membrane with the drying step of Allen. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Allen and Mahmoudi-Rad are directed towards intact human amniotic membrane compositions and their methods of preparation thereof. The skilled artisan would have been motivated to do so because Allen teaches that freezing amniotic membrane has known drawbacks such as lower levels of angiogenic factors, and so the substitution would be predictably advantageous to retain the angiogenic factors in the intact human amniotic membrane composition of Mahmoudi-Rad.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad and Thakoersing as applied to claim 1 above, and further in view of Werber et al (WO 2015/134936; of record in IDS filed 10/18/2021) and as evidenced by Malhotra et al. (World J Transplant (2014 June 24); 4(2): 111-121; Reference U) and Ma (“Density of Water” (2007), Retrieved from https://hypertextbook.com/facts/2007/AllenMa.shtml , 2 pages; Reference U2).
The teachings of Mahmoudi-Rad and Thakoersing are relied upon as set forth above. Mahmoudi-Rad further teaches cutting the intact human amniotic membrane into smaller pieces after obtaining said amniotic membranes from donor mothers (page 647, subheading “Preparation of amniotic membrane”), reading in-part on the contiguous piece claims 13-15.
Regarding claim 13, Mahmoudi-Rad and Thakoersing do not teach a contiguous piece of intact human amniotic membrane of at least 50mg. Regarding claim 14, Mahmoudi-Rad and Thakoersing do not teach a contiguous piece of intact human amniotic membrane of at least 100mg. Regarding claim 15, Mahmoudi-Rad and Thakoersing do not teach a contiguous piece of intact human amniotic membrane of at least 150mg.
Werber beneficially teaches a therapeutic composition comprising: acellular amniotic membrane; a carrier fluid, wherein the carrier comprises an acellular amniotic fluid (reads on “preservation media derived from” plasma), and wherein the therapeutic composition is essentially free of any viable amniotic membrane cells or viable amniotic fluid cells (reads on free of red blood cells), and wherein the acellular amniotic membrane fraction is combined with the amniotic fluid (see paragraphs [0004] and [0094]). Werber teaches an example wherein 8 square centimeters of amniotic membrane was used to make the product to further treat a deep cut in the heel of a subject in need thereof (see paragraph [0094]), reading on claims 13-15. Werber 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 on claims 13-15.
In so much that biological tissues are primarily composed of water, water has an inherent density of 1 about g/cm3 as evidenced by Ma (see Table 4 and Graph 4), and amniotic membrane is taught as inherently having a thickness of about 0.02-0.05 mm as evidenced by Malhotra (page 112, the 1st paragraph under “Structure of Fetal Membranes”), the weight of Werber’s amniotic membrane can be approximated by the following calculations: 8 cm x 8 cm x (0.02 to 0.05 mm) x (1 cm ÷ 10 mm) = 0.128-0.32 g, i.e. 128-320 mg and thus reading on the weight ranges of claims 13-15.
Regarding claims 13-15, it would have been obvious to further formulate the intact and contiguous human amniotic membrane composition of Mahmoudi-Rad to 8 cm2 in view of Werber and as evidenced by Malhotra and Ma to generate an intact and contiguous human amniotic membrane composition having a weight of about 128-320 mg. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Werber and Mahmoudi-Rad are in-part directed towards intact amniotic membrane compositions and their associated methods of preparation. The skilled artisan would have been motivated to do so because Werber teaches an example wherein 8 square centimeters of amniotic membrane was used to make the product to further treat a deep cut in the heel of a subject in need thereof, and so would predictably improve upon the amniotic membrane composition of Mahmoudi-Rad to treat subjects in need thereof.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad and Thakoersing as applied to claim 1 above, and further in view of and as evidenced by Daniel et al (US 2019/0192734).
The teachings of Mahmoudi-Rad and Thakoersing are relied upon as set forth above.
Regarding claim 19, Mahmoudi-Rad and Thakoersing do not teach the intact human amniotic membrane being further gelatinous. Regarding claim 20, Mahmoudi-Rad and Thakoersing do not teach the intact human amniotic membrane being further hydrophilic. However, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently is a spongy layer (see paragraphs [0004] and [0109]). Regarding claim 20, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently comprises hydrophilic molecules (see paragraphs [0008]). Therefore, the intact human amniotic membrane of Mahmoudi-Rad as evidenced by Daniel inherently reads on the gelatinous of claim 19 and the hydrophilic of claim 20; see M.P.E.P. § 2112.
Regarding claim 18, Mahmoudi-Rad and Thakoersing do not teach the intact human amniotic membrane being visibly clear.
Daniel teaches a composition comprising translucent, dehydrated placental tissue having improved visualization and/or handling characteristics. (Abstract), reading on claim 18. Daniel teaches that intact intermediate layer inherently can be formulated to be translucent by steps of dehydration and then rehydration (see Figure 2B and ¶0241), reading on claim 18. Daniel teaches that the amnion/chorion may be processed such as leave the epithelial layer intact (¶0108), reading on claim 18.
Regarding claim 18, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the intact human amniotic membrane of Mahmoudi-Rad to be visibly clear (e.g. translucent) in view of Daniel and Thakoersing. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Mahmoudi-Rad and Daniel are directed in-part towards intact human amniotic membrane compositions and their methods of preparation thereof. The skilled artisan would have been motivated to do so because Daniel teaches that dehydration and rehydrating the intact amniotic membrane is predictably advantageous to improve the visualization and/or handling characteristics of the membrane composition, and so the substitution would be predictably advantageous to improve the visualization and/or handling characteristics intact human amniotic membrane composition of Mahmoudi-Rad.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2 and 4-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-22 of copending Application No. 16/043,505
claims 1-23 of copending Application No. 14/945,128
when each is and as evidenced by Daniel et al (US 2019/0192734) and Haserodt et al (2011, Glycobiology, 21(2): 175–183).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘505 application is drawn to a method of making a acellular product comprising a concentrated plasma portion and a biological membrane portion, wherein the biological membrane portion is impregnated with the plasma portion, which is not distinct from the instantly claimed product. The ‘520 application is drawn to a method of using an acellular product comprising a plasma portion and a biological membrane portion, wherein the biological membrane portion is impregnated with the plasma portion, which is not distinct from the instantly claimed product. The ‘128 application is drawn to product of an acellular product comprising a plasma portion and a biological membrane portion, wherein the biological membrane portion is impregnated with the plasma portion, which is not distinct from the instantly claimed product.
Regarding claims 8-9 and 16-17, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently comprises hyaluronic acid and collagens (see paragraphs [0004] and [0109]). Regarding claim 19, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently is a spongy layer (see paragraphs [0004] and [0109]); reads on gelatinous. Regarding claim 18, Daniel is an inherency reference cited solely as evidence that intact intermediate layer inherently can be translucent (see Figure 2B). Regarding claim 20, Daniel is an inherency reference cited solely as evidence that the intermediate layer inherently comprises hydrophilic molecules (see paragraphs [0008]).
Regarding claim 1, Haserodt is an inherency reference cited solely as evidence that digestion of hyaluronic acid with hyaluronidase inherently breaks down the hyaluronic acid such that the low molecular weight hyaluronic acid cannot be detected (see Figure 1B). Additionally, the inherency reference Haserodt also specifically highlights that low molecular weight HA inherently cannot be detected by at least two ELISA kits (see abstract). It is noted that this is the same as the statement in paragraph [0156] of the as filed specification, which states “[t]he scaffold product digested with hyaluronidase did not yield detectable hyaluronic acid due to the low molecular weight of the fragments produced form this treatment which is below the molecular weight threshold for the ELISA used (data not shown).” Therefore, the limitation of “when digested with hyaluronidase, yields undetectable amounts of hyaluronic acid” as given the broadest reasonable interpretation consistent with the specification, is an inherent property as evidenced by Haserodt.
The reference applications are silent as to the functional properties of the product in claims 6-7, 10 and 12. The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' acellular product differs, and if so to what extent, from the acellular product discussed in the reference applications. The reference applications acellular product comprises the same structural materials as the claimed product, namely human amniotic intermediate layer and concentrated human amniotic fluid. The reference applications taken as a whole demonstrates a reasonable probability that the acellular product of the prior art is either identical or sufficiently similar to the claimed acellular product that whatever differences exist are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claim 3 is rejected provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-22 of copending Application No. 16/043,505
claims 1-23 of copending Application No. 14/945,128,
when each is and as evidenced by Daniel and Haserodt as applied to claims 1-2 and 4-20 above, and further in view of Samaniego et al (US 20150157761).
The teachings of the reference applications are discussed and relied upon above.
The reference applications not teach the amount of water removed during the concentration of the amniotic fluid (claim 3).
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% (see paragraphs [0008] and [0060]).
It would have been obvious to combine the reference applications and Samaniego to evaporate the fluid in the reference applications composition to a level of about 10%. A person of ordinary skill in the art would have had a reasonable expectation of success in evaporating the fluid in the reference applications composition to a level of about 10% because Samaniego establishes this is a suitable evaporation method. The skilled artisan would have been motivated to evaporate the fluid in the reference applications composition to a level of about 10% because Samaniego teaches this is a useful evaporation method for preparation of products for therapeutic uses and the reference applications establish that it is beneficial to concentrate the amniotic fluid.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 2, 5, 8, 9, 16, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 9 of U.S. Patent No. 12,551,509 (Reference A) as evidenced by Malhotra et al. (World J Transplant (2014 June 24); 4(2): 111-121; Reference U).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the ‘509 recites a composition comprising cellular placental product comprising a human amniotic plasma portion and an intact intermediate layer scaffold membrane portion; said intermediate layer being isolated from human amniotic membrane; said intact intermediate layer scaffold membrane portion being impregnated with said human amniotic plasma portion, and thus reading on instant claims 1 and 2. Claim 6 of the ‘509 patent reads on instant claims 8, 9, 16, and 17 as intact human amniotic membrane inherently comprises collagen and hyaluronic acid as evidenced by Malhotra (page 112-113, subheading “Basement membrane” and “Anti-fibrotic and anti-inflammatory properties”). Claim 9 of the ‘509 patent reads on instant claim 5.
Response to Arguments
Applicant's arguments on pages 4-6 of the reply have been fully considered, but not found persuasive of error. Every rejection of record in the final Office Action dated 9/17/2024 for the instant application was affirmed in the PTAB decision dated 3/11/2026, and the instant amendments to claim 1 do not overcome the 35 U.S.C. § 103 rejections of record over Werber, Werber2, and Koob as evidenced by Daniel and Haserodt as set forth above. The argument on page 4 of the reply that Application # 16/043,520 issued to a patent after the reversal of different 35 U.S.C. § 103 rejections on appeal is not persuasive as each patent application is prosecuted on its own merits and what was done in previous case(s) is not binding on the examiner nor the courts and does not constitute imprimatur for the prosecution of further cases. See In re Gyurik, 596 F.2d 1012, 201 USPQ 552 (CCPA 1979); In re Atwood, 267 F.2d 954, 122 USPQ 378 (CCPA 1959); In re Freedlander, 136 F.2d 759, 760, 58 USPQ 402, 403 (CCPA 1943).
Applicant’s arguments on page 5 of the reply regarding the nonstatutory double patenting rejections of record are not found persuasive of error. The rejections are maintained as set forth above.
Conclusion
No claims are allowed. No claims are free of the art.
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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