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 .
Applicants’ response of 2/4/2026 has been received and entered into the application file. Claims 1-23 are pending, of which claims 16-23 have been examined on the merits. Claims 1-15 remain withdrawn from consideration as being directed to non-elected inventions. Election being made with traverse on 7/9/2025.
Status of Prior Rejections/Response to Arguments
RE: Claim Interpretation:
Applicants state they disagree with the interpretation stated on the record. Applicants assert that decellularized human amniotic fluid cannot contain cellular material. This narrower limitation is not supported by the specification, nor the art accepted definition for “de-cellularized”. It is maintained that ‘decellularized’ means at least substantially free of whole cells.
RE: Rejection of claim 21 under 35 USC 112(b):
The amendment to claim 21 is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claim 18 under 35 USC 112(d):
The amendment to claim 18 is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 16-21 under 35 USC 102(a)(1) and 102(a)(2) over Behrens et al:
Applicants have traversed the rejection on the grounds that Behrens et al does not teach each and every limitation. Applicants argue that Behrens et al does not teach a decellularized human amniotic fluid. Applicants argue it is not clear that the centrifugation step of Behrens et al is followed by a subsequent step of collecting the less dense/upper/supernatant layers of the centrifuged sample.
This is not found persuasive. Behrens clearly states they are using AF that is “free of amniotic particulate matter, i.e. it has been clarified after collection” (See ¶0020). As centrifugation will pellet particulate matter to the bottom of the tube, the fact that Behrens states they are using AF that is free of amniotic particulate matter means they are collecting the less dense/upper/supernatant layers of the centrifuged samples that does not contain the particulate matter which is collected at the bottom of the tube (i.e. they collect the particulate-free supernatant). This is explicit in the example, wherein human amniotic fluid is obtained, pooled, centrifuged and the supernatant is preserved until use (See ¶0044).
Applicants’ argument at Pg 9 is not convincing. Applicants acknowledge that cells are larger/more dense than macromolecules. Thus cells would be pelleted down, along with cellular debris, while macromolecules would remain in the less dense/upper/supernatant layers, and recovered as part of the supernatant.
Claim 16 has been amended to require the D-HAF to be sterile. This is a new limitation. The rejection has been modified to address this limitation.
RE: [Provisional] Non-Statutory Double Patenting Rejections:
Applicants have traversed on the grounds that no evidence has been presented that any of the US Patents or co-pending US Patent applications contain claims to a composition as currently claimed.
This is not found persuasive. Each of the patents/co-pending US applications, in the independent claim, describe use of or production of a sterile, decellularized human amniotic fluid devoid of amniotic stem cells, elements of micronized membrane and chorion particles. Either independent or dependent claims in each patent further recite the presence of a pharmaceutically acceptable carrier. Furthermore, the sterile, decellularized amniotic fluid used in or made by the patents/copending applications are made by the same method as the instant application. Products made by the same method are necessarily of identical composition. The rejections are maintained, and extended to new claims 21-23..
Claim Interpretation
The claims refer to decellularized, human amniotic fluid (D-HAF). In accordance with its ordinary meaning in the art, the term “decellularized” is interpreted as meaning at least substantially free of whole cells (See, e.g. Werber et al, US Patent 9132156, at col. 2, ln 8-10, in describing “acellular”). A small number of residual cells present will still be reasonably interpreted as meeting the “decellularized” limitation. The D-HAF is not necessarily devoid of any other particulate matter.
Claim 16 is drawn to a composition comprising (i) sterile, D-HAF, and (ii) one or more pharmaceutically acceptable excipients and/or additives. Due to use of the word ‘comprising’, additional, un-recited components can further be present in the claimed composition. As such, the claimed composition can contain cellular material (including cells from amniotic fluid), cell debris (including from amniotic fluid) and more.
It is emphasized that independent claim 16 is to a composition comprising decellularized, human amniotic fluid and one or more pharmaceutically acceptable excipients and/or additives. The BRI of claim 16 permits for the composition to be in a fluid formulation. When the composition is in the form of a fluid composition, the D-HAF, even if previously lyophilized, will be reconstituted. As such, the limitations of claims 17-19 describing the D-HAF as being lyophilized and stored in a refrigerated condition are interpreted as product-by-process limitations. Reciting that the D-HAF was at one point lyophilized and stored in refrigerated conditions does not change the structure of the D-HAF in a final liquid formulation. Combining lyophilized D-HAF with a liquid excipient and/or additive (such as a physiologically acceptable saline solution) will serve to reconstitute the D-HAF.
Claim 20 defines the process by which the D-HAF is prepared. This is a product-by-process limitation. Product-by-process limitations are considered only in so far as the process of production affects the structure (physical and/or biochemical) of the final product. In the instant case, steps (a)-(c) as recited in claim 20 are understood to result in a supernatant that comprises at least the fluid portion of amniotic fluid and at least a reduced amount of particulate matter compared to raw amniotic fluid. Reference is made to Example 1 of the instant specification, which describes processing amniotic fluid via steps (a)-(c) of current claim 20. At pg 29, ln 1-2, the specification states that “If the supernatant still contains residual insoluble components, it may be pre-filtered with 5 to 10 µ cellulose ester capsule….” This is taken to evidence that steps (a)-(c) of claim 20 do not necessarily remove all particulate matter or insoluble components from amniotic fluid. Furthermore, the limitations of claim 20 are only directed to creation of the D-HAF component, the claimed composition is to a composition comprising D-HAF.
Claim Rejections- 35 USC § 112
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16-23 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Behrens (US 2008/0286378).
Behrens et al disclose methods and compositions comprising amniotic fluid for treatment of ocular diseases (See ¶0008). The amniotic fluid can be human amniotic fluid (See ¶0018). The amniotic fluid is free of amniotic particulate matter, i.e. it has been clarified after collection (See ¶0020). Techniques for clarifying amniotic membrane particulate matter from amniotic fluid include, but are not limited to, centrifugation, including centrifugation at a speed up to about 5,000 rpm (See ¶0020). It is submitted that “free of amniotic membrane particulate matter” will also mean the composition is substantially free of cells, noting that cells are larger in size and weight than cell debris, thus centrifugation sufficient to remove cell debris will also necessarily remove cells.
Behrens et al teach the amniotic fluid can be lyophilized and stored, and then reconstituted for use. Reconstitution may be carried out with physiologically compatible saline solutions (See ¶0023).
Behrens et al teach the amniotic fluid can be sterilized, such as by gamma irradiation (See ¶0021).
Regarding claim 16: The embodiment wherein the clarified amniotic fluid is lyophilized, and then reconstituted with a physiologically compatible saline is relied upon. The reconstituted composition reads on the composition of claim 16. Specifically, the clarified amniotic fluid composition of Behrens et al which is free of amniotic membrane particulate matter, clarified by centrifugation is considered to inherently read on the D-HAF. This conclusion is based on the finding that cells are larger in size and weight than cell debris, thus centrifugation sufficient to remove cell debris will also necessarily remove cells. The amniotic fluid can be human amniotic fluid.
The physiologically compatible saline reads on one or more pharmaceutically acceptable excipients.
Regarding claim 17: Following the discussion of claim 16 above, the D-HAF reconstituted with physiologically compatible saline is in a fluid form.
Regarding claim 18: Following the discussion of claim 16 above, the D-HAF is first lyophilized, and can be sterilized by gamma irradiation (which reads on gamma ray irradiation). The D-HAF is in lyophilized form. The lyophilized D-HAF is then reconstituted with the physiological saline.
Regarding claims 19-21: As discussed above under Claim Interpretation, these claims describe how the D-HAF component is treated/obtained prior to provision in the claimed composition. These limitations do not distinguish the claimed composition from the reconstituted, clarified human amniotic fluid composition of Behrens et al. The previous storage conditions of the D-HAF component do not affect the final composition. However, it is noted that Behrens et al teach the composition can be stored in refrigerated conditions (See ¶0022).
Regarding claim 22: Following the discussion of claim 16 above, Behrens teach the amniotic fluid is free of particulate matter. As amniotic stem cells, elements of micronized membrane and chorion particles are all examples of particulate matter, the particulate matter-free composition of Behrens is necessarily free of each of these components.
Regarding claim 23: The growth factor content of D-HAF is an inherent property thereof. Given that Behrens produces the amniotic fluid free of particulate matter in the same manner as taught by the instant specification (centrifugation), and noting that Behrens et al teach macromolecules are not removed (growth factors are examples of macromolecules), there is reasonable basis to conclude that the amniotic fluid free of particulate matter of Behrens et al contains the same variety of growth factors that are present in the D-HAF as the instant application.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 16-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over each of:
Claims 14 and 17 of U.S. Patent No. 9884078,
Claim 11 of U.S. Patent No. 9579350,
Claims 4-6 of U.S. Patent No. 9907821,
Claims 6-7 of U.S. Patent No. 11571187,
Claim 17 of U.S. Patent No. 10485521,
Claim 14 of U.S. Patent No. 10519420,
Claims 4-6 of U.S. Patent No. 11273183,
Claim 3 of U.S. Patent No. 11491189, and
Claims 3, 13 and 14 of U.S. Patent No. 11633432.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims claim a composition that comprises sterile D-HAF and a pharmaceutically acceptable excipient and/or methods of using said composition (methods of use will anticipate the product, per se). The limitations of claims 17-21 are directed to product-by-process limitations related to the process of producing the D-HAF component. The D-HAF of the patents is identical to the D-HAF of the current claims, as they are produced by the same methods (see patent specifications).
Claims 16-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over each of:
claims 1-20 of copending Application No. 18/121385 (reference application),
claim 8 of copending Application No. 17/933374 (reference application),
claims 9, 13 and 15-17 of copending Application No. 18/409746 (reference application), and
claims 15 and 18 of copending Application No. 18/770542 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference applications claim a composition that comprises D-HAF and a pharmaceutically acceptable excipient and/or methods of using said composition (methods of use will anticipate the product, per se). The limitations of claims 17-21 are directed to product-by-process limitations related to the process of producing the D-HAF component. The D-HAF of the reference application is identical to the D-HAF of the current claims, as they are produced by the same methods (see reference application specifications).
These are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633