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 .
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-3, 5-7, 10, 12, and 19-20 drawn to a method of preparing a fetal support tissue product and species election of umbilical cord amniotic membrane (claim 5) in the reply filed on February 12, 2026 is acknowledged.
Claims 21, 23-26, 31, and 45-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions and claim 6 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 4, 8-9, 11, 13-18, 22, 27-30, and 32-44 were previously canceled. Claims 6, 21, 23-26, 31, and 45-46 have been withdrawn.
In view of the prior art, the species of placental amniotic membrane (claim 5) has been rejoined.
Claims 1-3, 5, 7, 10, 12, and 19-20 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US2021/056518, filed on October 25, 2021. The instant application claims 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) to U.S. provisional applications 63/105770, filed on October 26, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 2, 2023; October 9, 2024; and February 12, 2026 are in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Objection to Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description:
Figures 2C and 2D are not detailed in Para. [00224] of the Specification.
Figure 6 of the Specification does not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(o)). Specifically, there is no legend describing Group A or B or A1-A4 and B1-B4 and no mention of those
Figures 8 A-D of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, all the labels for the figures are illegible.
Figures 11A-C of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the quality of the images make the legend shapes difficult to discriminate from one another, the labels for the legend shapes difficult to read, and the y-values illegible. Additionally, Fig 11 appears to be missing a label for Fig 11C.
Figures 11A-C are not detailed in Para. [00246] of the Specification. Para. [00246] appears to incorrectly reference Figure 12 instead of Figures 11A-C.
Figures 13A, 13D-F of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the labels for the images are illegible.
Additionally, Para. [00264] appears to incorrectly reference various aspects of Figs 13A-F including a lane 17 in Figure 13C which is not present, Group B in lanes 6-8 of Fig 13E which appear to be labeled Group A, and correlation of Fig 13F with baseline samples in Fig 13B which appears to not show the same samples at all. It is recommended that Applicant carefully review the Figures and Specification to amend any errors.
Figures 15A-B appear to contain labels for samples A3 and B3 while Para. [00266] references Figs 15A-B as baseline values for samples A4 and B4.
Figures 16A-B of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the quality of the images is poor which precludes any demonstration of results.
Figure 17A of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the labels for the figure are illegible.
Figures 20A, 21A, and 22A of the Specification does not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the quality of the images is poor which precludes any demonstration of results.
Additionally, Para. [00293] details Figure 21B as showing WST-1 assay; Figure 21B is labeled as an M2 assay. Para. [00294] details Figure 22B as showing an M2 assay; Figure 22B is labeled as an NO assay.
Figure 23 of the Specification appears to show a flowchart which is not referenced in the description. Para. [00295] of the specification references Figures 23A-23B showing NO production.
Figures 24A-C of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the flowcharts are illegible.
Additionally, Figures 24A-C are not detailed in the Specification.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application.
Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Objections to the Specification
The use of the term Pluronics F86, F88, F108, and F127 (Para. [00113]), which are trade names or a marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-2, 10, 12, and 19 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.
Claim 1 recites the limitation "the fetal support tissue" in line 2. There is insufficient antecedent basis for this limitation in the claim as there is no prior recitation of a fetal support tissue. Appropriate correction is required.
Claim 2 recites the limitation "a membrane having a pore size of about 0.2-0.3 µm or less" in line 2. Claim 2 depends from claim 1 which recites two membranes which have different pore sizes, 0.7 µm or less and 0.4 µm or less. Based on its dependency, claim 2 is interpreted as intending to further limit the membranes as recited in claim 1 but it is unclear which membrane of claim 1 is to be replaced with 0.2-0.3 µm filter membrane, thus rendering the scope of the claim indefinite.
Claim 10, which depends from claim 1, recites the limitation of the method further comprising centrifuging the fetal support tissue following step (b) of claim 1. Claim 1 recites that step (a) produces a homogenized fetal support tissue and step (b) produces an extract comprising homogenized fetal support tissue and an excipient. As instantly claimed, claim 10 recites centrifuging the fetal support tissue, which is the starting product of claim 1, after step (b) which produces an extract of homogenized fetal support tissue, thus rendering the scope of the claim indefinite. As claimed, it is unclear how one would centrifuge the fetal support tissue after generating an extract of homogenized fetal support tissue. Appropriate correction is required.
Claim 12, which depends from claims 10 and 1, recites the limitation comprising diluting the fetal support tissue following the centrifugation in claim 10. As detailed above, the fetal support tissue is the starting product of claim 1. As instantly claimed, claim 12 requires centrifuging the starting product of claim 1 after step (b) which produces an extract of homogenized fetal support tissue and further diluting the starting product of claim 1, thus rendering the scope of the claim indefinite. As claimed, it is unclear how one would dilute fetal support tissue after centrifuging an extract of homogenized fetal support tissue. Appropriate correction is required.
Claim 19, which depends from claims 12, 10, and 1, recites the limitation wherein the diluted fetal support tissue comprises about 1 µg/ml to about 150 µg/ml hyaluronan. As detailed above, the fetal support tissue is the starting product of claim 1. As instantly claimed, claim 19 requires centrifuging the starting product of claim 1 after step (b) which produces an extract of homogenized fetal support tissue and further diluting the starting product of claim 1, thus rendering the scope of the claim indefinite. As claimed, it is unclear how the diluted fetal support tissue starting product of claim 19 is to be generated. Appropriate correction is required.
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 1-3, 5, 7, 10, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Tseng et al. (US 9,682,044, found in IDS dated 08/02/2023, hereafter “US ‘044”) in view of Corning Filtration Guide (2009, retrieved 07/31/2025, https://web.arch ive.org/web/20200929003355/https://www.corn ing.com/catalog/cls/document s/selection-guides/t_filterselectionguide.pdf, pp. 1-20; found in IDS dated 02/12/2026).
With regard to claims 1 and 2, US ‘044 teaches generation of a fetal support tissue product (Abstract) comprising “grinding” of fetal support tissue (Col. 30, lines 57-58) which can include homogenizing (Col. 24, lines 5-8) and include use of a freezer/mill (Col. 31, line 6) as instantly disclosed in Para. [00220] of the specification. US ‘044 teaches that a buffer or water can be mixed with the resultant ground fetal support tissue (Col. 33, lines 38-40) in order to form a solution (Col. 37, line 36), which is considered to reasonably read generating an extract of fetal support tissue via mixture with an excipient (see also Example 9).
US ‘044 teaches that the powdered fetal tissue support product can be terminally sterilized via any medically acceptable method (Col. 35, lines 45-47) and several examples of treatment using fetal support tissue product where the fetal support tissue is in a liquid formulation (e.g., See Examples 12, 13, 14, 15, and 24). However, despite the fact that sterilization by filtration is a technique widely known in the art, US ‘044 is silent as to sterilization via filtering for a liquid fetal support tissue product.
Corning Filtration Guide teaches that sterilization of biological fluids can be done using a filter having a pore size of 0.2 µm or 0.22 µm as recited in claim 2 (Pg. 3, Step 1 and Table 1) and that clarification and prefiltration of solutions can be can be done to improve filter performance using a filter having pore size of 0.45 µm or larger and (Pg. 3, Step 1 and Table 1). Thus, the Corning Filtration Guide teaches that sterilization of biological fluids can be performed via prefiltration using a filter membrane of 0.45 µm or greater, which is considered to reasonably read on a membrane having a pore size of 0.7 µm or less followed by use of a filter membrane having a pore size of 0.2 µm or 0.22 µm, which is considered to reasonably read on a membrane having a pore size of 0.4 µm or less as recited in claim 1.
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the instant invention to choose sterilization via filtration as taught by the Corning Filtration Guide for use in the method of producing a fetal support tissue product comprising homogenizing fetal support tissue and generating an extract via addition of an excipient as taught by US ‘044 with a reasonable expectation of success. US ‘044 teaches that for sterilization of a fetal tissue support product can be via any suitable method (Col. 35, lines 46-47), that the fetal support tissue product can be in a “syringeable” aqueous form (Col. 37, lines 29-34), and examples where the fetal support tissue product is administered via injection (Ex. 12-15). Sterilization by filtration is a technique widely known and used in the art and which can be performed fairly quickly, easily, and inexpensively. Thus a skilled artisan would have been motivated to choose sterilization by filtration using filters having pore sizes as taught by the Corning Filtration Guide in order to produce a fetal support tissue product in aqueous form which is sterile and can be safely administered to a subject for treatment.
Additionally, it is noted that the instant specification does not provide a definition for what is to be considered “about” related to the pore sizes in the membrane used for sterilization by filtering. As such, the broadest reasonable interpretation of “about” 0.7 µm includes sizes from 0.07 µm to 7 µm, the broadest reasonable interpretation of “about” 0.4 µm includes sizes from 0.04 µm to 4 µm, and the broadest reasonable interpretation of “about” 0.2-0.3 µm includes sizes from 0.02-0.03 µm to 2-3 µm.
With regard to claim 3, US ‘044 teaches that homogenization of fetal support tissue can comprise use of a pulverizer (e.g. Corvaris Cryoprep) (Col. 30, line 66) or a freezer/mill (Col. 31, line 6) as instantly disclosed in Para. [00220] of the specification, and can be performed at temperatures below 0° C/submerged in liquid nitrogen (Col. 31, lines 30-37), which is considered to reasonably read on cryopulverizing.
With regard to claim 5, US ‘044 teaches that the fetal support tissue can be placental amniotic membrane (Col. 1, line 44) and/or umbilical cord amniotic membrane (Col. 27, line 67; see also Col. 32, lines 57-59).
With regard to claim 7, US ‘044 teaches that the fetal support tissue product can be mixed with saline (Col. 33, line 44).
With regard to claim 20, US ‘044 teaches that the fetal support tissue product is anti-inflammatory (Col. 3, line 21).
Claims 10, 12 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over US ‘044 and Corning Filtration Guide as applied to claim 1 above, and further in view of Tseng et al (US 8,153,162, found in IDS dated 08/02/2023, hereafter “US ‘162’).
With regard to claim 10, as detailed above, the combination of US ‘044 and Corning Filtration Guide teaches a method of preparing a fetal support tissue product comprising homogenizing a fetal support tissue, adding an excipient in order to make a fetal support tissue extract, and sterilizing by filtration using a filter membrane having a pore size of 0.7 µm or less followed by a filter membrane having a pore size of 0.4 µm or less.
The combination of ‘044 and Corning Filtration Guide is silent regarding centrifuging the fetal support tissue.
US ‘162 teaches an extract of amniotic membrane (Col. 13, line 63) derived from the placenta (Col. 13, line 64), which is considered to reasonably read on a fetal support tissue product, prepared by pulverizing amniotic membrane in liquid nitrogen (Col. 14, lines 1-4), which is considered to reasonably read on homogenizing; and adding PBS (Col. 14, line 4), which is considered to reasonably read on adding an excipient; in order to form an amniotic membrane extract (Col. 14, lines 12-13). US ‘162 teaches that the amniotic membrane extract can be centrifuged (Col. 14, lines 15-16) and that centrifugation can be used to remove large particles from the fetal support tissue extract (Col. 11, line 64-65).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to apply a method step comprising centrifuging after adding an excipient as taught by US ‘162 to the method of preparing a fetal support tissue product comprising homogenizing a fetal support tissue, adding an excipient to produce an extract, and sterilization by filtration as taught by the combined teachings of US ‘044 and Corning Filtration Guide. A skilled artisan would have recognized that centrifuging the extract prior to filtration could be used to remove any large particles of fetal tissue which would help reducing clogging of the membrane during the filtration/sterilization process. A skilled artisan would have had a reasonable expectation of success as both US ‘044 and US ‘162 teach production of a fetal support tissue product comprising homogenization and addition of an excipient and centrifugation is a commonly used technique well known to those having ordinary skill in the art.
With regard to claim 12, as detailed above, the combination of US ‘044 and Corning Filtration Guide teaches a method of preparing a fetal support tissue product comprising homogenizing a fetal support tissue, adding an excipient in order to make a fetal support tissue extract, and sterilizing by filtration using a filter membrane having a pore size of 0.7 µm or less followed by a filter membrane having a pore size of 0.4 µm or less.
The combination of ‘044 and Corning Filtration Guide is silent regarding centrifuging the fetal support tissue and dilution after centrifuging.
US ‘162 teaches that the fetal support tissue extract can be centrifuged (Col. 14, lines 15-16) after addition of the excipient in order to remove any remaining large particles (Col. 11, line 64-65) and lyophilized (Col. 14, line 23). Additionally, US ‘162 teaches that lyophilized fetal support tissue can be reconstituted in a suitable buffer prior to use (Col. 12, lines 58-60), that the concentration of the fetal support tissue can be varied as needed (Col. 12, lines 61-62), and that additional compounds (including buffers) can be added to the reconstituted fetal support tissue in order to reach the desired concentration (Col. 12, lines 65-67 and Col. 13, lines 1-4).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to apply addition of buffers to reconstituted lyophilized fetal support tissue product (i.e., dilution) after the fetal support tissue product has been centrifuged as taught by US ‘162 to the method of preparing a fetal support tissue product as taught by the combination of US ‘044 and Corning Filtration Guide with a reasonable expectation of success. A skilled artisan would be motivated to apply dilution of a fetal support tissue product because US ‘162 teaches that the desired amount of fetal support tissue in a preparation can vary based on the intended use of the product and that lower concentrations of fetal support tissue in a preparation is desired for some procedures (Col. 12, lines 62-64). A skilled artisan would have had a reasonable expectation of success as both US ‘044 and US ‘162 teach compositions comprising fetal support tissue produced by homogenization and addition of an excipient which have therapeutic uses. Additionally, dilution of solutions in order to modify concentrations is a commonly used technique well-known to those having ordinary skill in the art.
With regard to claim 19, as detailed above, the combination of US ‘044 and Corning Filtration Guide teaches a method of preparing a fetal support tissue product comprising homogenizing a fetal support tissue, adding an excipient in order to make a fetal support tissue extract, and sterilizing by filtration using a filter membrane having a pore size of 0.7 µm or less followed by a filter membrane having a pore size of 0.4 µm or less. US ‘162 teaches that the fetal support tissue extract can be centrifuged (Col. 14, lines 15-16) after addition of the excipient in order to remove any remaining large particles (Col. 11, line 64-65) and lyophilized (Col. 14, line 23).
US ‘044 teaches that fetal support tissue comprises hyaluronic acid (i.e., hyaluronan) (Col. 45, line 43) which can diffuse out of the fetal support tissue product (Col. 45, lines 50-51), but is silent as to the specific amount of HA in the fetal support tissue.
US ‘162 teaches that the fetal support tissue product comprises hyaluronan (HA) (Col. 9, line 47) and that fetal support tissue extracts prepared with a 1:1 ml/g ratio of PBS and fetal support tissue, centrifuged, lyophilized, and reconstituted with water (See “Amniotic Membrane Extract Preparations, starting at Col. 13, line 63) comprise 44-75 µg/ml of HA (Table 1). US ‘162 also teaches that the amount of HA can be assayed with a HA Quantitative Test Kit (Example 2).
Therefore, as US ‘162 teaches a fetal support tissue comprising a target final concentration of 44-75 µg/ml of HA, it would have been obvious to one having ordinary skill in the art as an intermediate HA target concentration for dilution of fetal support tissue, for example to be able to assay the diluted fractions for therapeutic benefit at various points in the purification process.
Additionally, it is noted that the instant specification does not provide a definition for what is to be considered “about” related to the concentration of HA in a diluted fetal support tissue. As such, the broadest reasonable interpretation of “about” 1 µg/mL to about 150 µg/mL includes ranges of HA amounts from about 0.1 µg/ml to about 1.5 mg/ml.
Prior Art Made of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Liu et al. (US 8,071,135 and PG Pub US 20080181967, found in IDS dated 08/02/2023) teaches compositions comprising fetal support tissue and methods of making compositions comprising fetal support tissue including disrupting the fetal support tissue by homogenizing in an aqueous solution (Para. {0057]). Liu et al. further teach that compositions of the invention can be sterilized by any means known in the art, including filtration using a pore size less than about 0.45 microns or less than about 20 nanometers (Para. [0094]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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/ERIN V PAULUS/Examiner, Art Unit 1631 /ARTHUR S LEONARD/Examiner, Art Unit 1631