DETAILED ACTION
Status of Application
The Examiner acknowledges receipt of the amendments filed on 12/17/2025 wherein claims 63, 64, 67 and 68 have been amended and claims 69-74 have been added.
Claims 63-74 are presented for examination on the merits. The following rejections are made.
Response to Applicants’ Arguments
Applicant’s arguments/amendments filed 12/17/2025 regarding the rejection of claims 67 and 68 made by the Examiner under 35 USC 112(b) have been fully considered and they are considered persuasive. This rejection is withdrawn as the range is not an endpoint as previously understood but a breadth.
Applicant’s arguments filed 12/17/2025 regarding the rejection of claims 63 and 64 made by the Examiner under 35 USC 102(a)(1) over Mitsialis et al. (US 2017/0258840), evidenced by Azevedo et al. (Critical Care, 2007, 11(6), 1-10) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 8/22/2025.
Applicant’s arguments filed 12/17/2025 regarding the rejection of claims 63 and 64 made by the Examiner under 35 USC 102(a)(1) over Azevedo et al. (Critical Care, 2007, 11(6), 1-10) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 8/22/2025.
Applicant’s arguments filed 12/17/2025 regarding the rejection of claims 63-66 made by the Examiner under 35 USC 103 over Mitsialis et al. (US 2017/0258840), evidenced by Azevedo et al. (Critical Care, 2007, 11(6), 1-10) in view of Imbrie et al. (WO 2013/048734) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 8/22/2025.
Applicant’s arguments filed 12/17/2025 regarding the rejection of claims 63, 64, 67 and 68 made by the Examiner under 35 USC 103 over Mitsialis et al. (US 2017/0258840), evidenced by Azevedo et al. (Critical Care, 2007, 11(6), 1-10) in view of Lim (US 2014/0031256) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 8/22/2025.
In regards to the 102(a)(1) and 103 rejections over Mitsialis and Azevedo, Applicant asserts the following:
Mitsialis does not disclose making exosomes according to the process utilized by the claims which results in a smaller mean diameter and smaller size distribution range. Thus, the exosomes of the claims are different than Mitsialis; and
Azevedo cannot disclose the exosomes claimed as the reference fails to teach a freezing/thawing cycle as instantly required.
In response to A, it is not clear that the size distribution of Mitsialis exosomes are any different from that claimed. Independent claim 63 does not require any size limitation and importing such a limitation without being present would be unreasonably limiting. Claim 64 requires the exosomes have a diameter no greater than 300 nm. Mitsialis discloses that their exosomes are to be spherical and have a diameter of 10-150 nm (or 30-100 nm) (see [0008, 0108]). While there may be differences between the isolated exosomes of the product-by-process used to make the claimed composition, the Examiner is not persuaded that the size distribution is it.
In response to B, the freeze-thaw cycle is ultimately a product-by-process limitation and it is not clear what differences, if any, the exosomes prepared by the present process would possess compared to the exosomes isolated by the process of Azevedo. Applicant points to a narrower size distribution of the purified exosomes but as noted for Mitsialis independent claim 63 does not require any size distribution and the range of claim 64 is anticipated by the Azevedo (100 nm).
Maintained Rejections (63-68) and New Rejections (claims 69-74)
Claim Rejections - 35 USC § 102
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.
Claims 63, 64, 69 and 70 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mitisialis et al. (US 2017/0258840; of record), evidenced by Azevedo et al. (Critical Care, 2007, 11(6), 1-10).
Mitisialis discloses compositions comprising isolated exosomes. The exosomes are to be isolated from blood. It is noted that blood contains platelets (see evidence to Azevedo) and so the isolated exosomes of Mitisialis would necessarily include platelet-derived exosomes. The isolated exosomes are to have a diameter of between 30-100 nm (see [0004]) (e.g. not greater than 300 nm) (see instant claim 64) and may be cryopreserved/lyophilized (i.e. cryodesiccated) so as to enable long-term storage (see [0038, 0091]) (see instant claim 69).
Claims 63 and 64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Azevedo et al. (Critical Care, 2007, 11(6), 1-10).
Azevedo discloses isolated platelet-derived exosomes which have a diameter of approximately 100 nm (see page 2). Figure 1 indicates that the isolated exosomes are spherical/spheroid.
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.
Claims 63-66 and 69-72 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitisialis et al. (US 2017/0258840; of record), evidenced by/in view of Azevedo et al. (Critical Care, 2007, 11(6), 1-10), in view of Imbrie et al. (WO 2013/048734).
Mitisialis and Azevedo are relied upon for disclosure described in the rejection of claim 63, 64, 69 and 70 under 35 U.S.C. 102(a)(1).
Mitisialis’ composition can take a variety of forms such as suspensions, injectable formulations, capsules and so on (see [0089-0091]) wherein the composition is to include a variety of formulatory agents such as suspending, stabilizing and/or dispersing agents (see [0091]).
Mitisialis fails to teach the composition as comprising a biocompatible matrix comprising collagen, thrombin, gelatin, alginate, or another naturally occurring basement membrane product.
Imbrie describes an exosome containing medical formulation. The formulation may be in the form of an oral dosage form, e.g. capsules/tablets, or parenteral dosage forms, e.g. solutions/suspensions (see page 67). Exemplified excipients included in the dosage forms include binders such as alginic acid (alginate) and gelatin (see page 67) (see instant claims 66 and 72). The inclusion of the obvious excipients would necessarily result in a biocompatible matrix. It would have been obvious to modify Mitisialis’ composition to include other known excipients, such as alginate and gelatin, as the said excipients were known to be useful in delivering exosomes for therapeutic benefit. See MPEP 2143(I)(A) which states that combining prior art elements according to known methods to yield predictable results is supportive of obviousness.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claims 63, 64, 67-70, 73 and 74 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitisialis et al. (US 2017/0258840; of record), evidenced by/in view of Azevedo et al. (Critical Care, 2007, 11(6), 1-10), in view of Lim (US 2014/0031256).
Mitisialis and Azevedo are relied upon for disclosure described in the rejection of claim 63, 64, 69 and 70 under 35 U.S.C. 102(a)(1).
Mitisialis fails to teach 95% of the exosomes that have a diameter that falls within a distribution range of 100 nm.
Lim teaches composition comprising isolated exosomes. Lim teaches that exosomes may be sized by size fractionation and filtration through a membrane with a relevant size cutoff (see [1072]). Exemplified diameter range include between 50 nm to 150 nm (see [0171]) (see instant claim 67).
As it was known that the size of the exosomes in the final composition could be selected for by using physical means, e.g. filtration, the selection of a specific particle size distribution from within the broader known range would have been an obvious manipulation of the prior art. Thus, if one of ordinary skill determined that a 95% particle distribution of 100 nm exosomes resulted in a suitable therapeutic outcome, then such a result would have been the product of ordinary skill and common sense rather than of innovation. See MPEP 2144.05(II)(B).
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
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 extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611