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 .
Examiner's Note
The Remarks filed on 05/14/2024 indicate that claim 12 is presented as originally filed. However, the claims filed on 05/14/2024 indicate that claim 12 is amended. Clarification of this discrepancy is requested. For purposes of the present Office Action, claim 12 has been examined as currently amended, consistent with the claims filed on 05/14/2024.
Claim Status
Claims 1-18 are pending.
Claims 1-18 have been examined.
Claims 1-18 are rejected.
Priority
Acknowledgment is made of applicant's assertion that the present application is the §371 U.S. National Stage of International Application No. PCT/ PCT/US2022/050121, filed 11/16/2022, which claims the benefit of U.S. Provisional Application Serial No. 63/279,839, filed on 11/16/2021.
Claims 1-15 are entitled to the benefit of the provisional application filed on 11/16/2021, as the subject matter of these claims is adequately supported in the provisional application.
Claims 16-18 are newly added and lack support in the provisional application filed on 11/16/2021. Specifically, these claims recite “disruption” and “rupture” of a tendon, which are not described in the provisional claims or specification in the manner now claimed. Although the term “rupture” appears in the provisional specification, it does not denote identification or diagnosis of an acute tendon tear, but instead refers to structural and biological limitations of the healing response, particularly in chronic (degenerative) conditions, that may predispose the tissue to re-rupture. Accordingly, claims 16-18 are not entitled to the benefit of the provisional filing date and are accorded the effective filing date of the present nonprovisional application filed on 11/16/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/05/ is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The drawings filed on 5/14/2024 are accepted.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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.
[1] Claims 1-8 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Behfar et al. (WO2019118817A1, Published 06/20/2019).
With regard to claims 1 and 10, the reference teaches a composition comprising a purified exosome product (PEP) combined with a collagen-based supportive matrix to form bio-scaffold gel (see, reference claims 1, 9 and 10; page 12, lines 5-6; inter alia). Accordingly, the reference anticipates all limitation recited in claims 1 and 10.
With regard to claims 2-7, the reference teaches that the PEP comprises spherical or spheroid exosomes having a diameter no greater than 300 nm, spherical or spheroid exosomes having a mean diameter of 110 nm ± 90 nm (i.e., 20 nm to 200 nm), spherical or spheroid exosomes having a mean diameter of 110 nm ± 50 nm (i.e., 60 nm to 160 nm), spherical or spheroid exosomes having a mean diameter of 110 nm ± 30 (i.e., 80 nm to 140 nm), comprises from 1 % to 20% CD63- exosomes and from 80% to 99% CD63+ exosomes, and comprises at least 50% CD63- exosomes (see, reference claims 1, 4-5; page 1, lines 27-29; page 11, lines 9-21, inter alia). Accordingly, the reference anticipates all limitation recited in claims 2-7.
With regard to claim 8, the reference teaches that the PEP comprises 6 x 1011 particles/mL (FIG. 14; page 21, line 9), which constitutes a specific value within the claimed range of 1 x 1011 to 1 x 1013. Accordingly, the reference anticipates all limitation recited in claim 8.
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 (i.e., changing from AIA to pre-AIA ) 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.
[2] Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Behfar et al. (WO2019118817A1, Published 06/20/2019).
Behfar et al. has been described above to anticipate claims 1-8 and 10.
With regard to claim 9, which depends from claim 8, and ultimately from claim 1, the reference teaches that PEP preparations consistently yield approximately 6 x 1011 exosomes per mL. This disclosure demonstrates that the reference provides particle concentrations within the range recited in claim 8 (see reference claims 48 and 51; page 5, lines 16-22; page 21, lines 1-9; FIG. 14). A person of ordinary skill in the art would have been motivated to select or adjust the PEP concentration as appropriate for therapeutic use. Selecting a narrower concentration within this known range, as recited in claim 9, amounts to routine optimization of a result effective variable. Accordingly, claim 9 is rendered obvious over the reference.
With regard to claims 11, which depends from claim 10, and ultimately from claim 1, the reference teaches that PEP compositions may be combined with a collagen based supportive matrix to provide structural support and facilitate tissue repair (see, reference claims 9 and 10; page 3, lines 17-18; page 12, lines 5-6; FIG. 1, inter alia). The specification further discloses the use of various collagen types and explains that combining PEP with collagen enhances gel formation, improves localization of PEP, and promotes regenerative effects (see reference page 13, lines 24-31; page 14, lines 1-24). In view of this teaching, a person of ordinary skill in the art would have been motivated to select type I fibrillar collagen, a well-characterized and commonly used collagen type for musculoskeletal and tendon scaffolds, in order to achieve predictable structural support and regenerative outcomes. Accordingly, claim 11 is rendered obvious over the reference, as the reference teaches PEP compositions combined with collagen scaffolds, and the selection of type I fibrillar collagen constitutes routine optimization of known scaffold material.
With regard to claim 12, the reference teaches compositions comprising PEP combined with supportive matrices for use in tissue repair and regeneration, including musculoskeletal tissues (see reference page 3, lines 17-20; FIG. 1, inter alia). Application of the disclosed PEP composition to injured tendon tissue represents a predictable use of the composition for its intended regenerative purpose. Furthermore, the instant specification confirms that the disclosed methods may be practiced to repair “any damaged tendon at any site in the body,” thereby indicating that tendon treatment broadly was contemplated and is not limited to a particular tendon model (see instant application page 4, lines 5-10). Accordingly, the use of the reference composition for tendon repair would have been obvious to a person of ordinary skill in the art.
With regard to claims 13-15, the reference teaches that PEP compositions promote structural regeneration and improved collagen organizations when applied to damaged tissues. The claimed outcomes of decreasing adhesion formation (instant claim 13), an increased type I to type III collagen ratio (claim 14), and more organized collagen architecture (claim 15) represent predictable biological effects resulting from the application of regenerative exosome compositions to injured tendon tissue (see reference FIG. 6, FIG. 7, FIG. 11, FIG. 15, ; page 6, lines 6-10, inter alia). These functional limitations merely recite expected results of tissue regeneration and therefore do not confer patentable distinction over the reference. Accordingly, claims 13-15 are rendered obvious over the reference.
[3] Claims 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Behfar et al. (WO2019118817A1, Published 06/20/2019) as applied to claims 1-15 above, and further in view of Wellings EP et al. (Orthopaedic Journal of Sports Medicine, vol. 9 (12) 23259671211062929, Published 12/17/2021).
As discussed above, Behfar et al. renders claims 1-15 obvious.
With regard to claims 16-18, the reference teaches application of a purified exosome product (PEP) loaded onto a collagen scaffold to injured tendon tissue in an in vivo Achilles tendon model to determine whether the tendon’s intrinsic regenerative capacity could be improved (reference page 1, Title, Purpose, Methods, inter alia). The surgically transected Achillies tendon constitutes a tendon disruption and rupture model, thereby explicitly teaching the limitations of claims 16-18. Because the reference discloses applying the PEP composition to injured Achillies tendon tissue, it anticipates the method of treating injured tendon tissue as recited in claim 12 and, therefore, anticipates all limitations of claims 16-18.
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of Wellings EP et al. with those of Behfar et al. to apply the disclosed exosome compositions and methods to the treatment approach recited in claims 16-18, as Wellings EP et al. provides evidence of the relevant biological effects and therapeutic context, thereby supplying motivation to use the exosome products of Behfar et al. in the claimed manner with reasonable expectation of success.
[4] Claims 1-7 and 10-18 are rejected under 35 U.S.C. 103 as being unpatentable over Shen (WO2020102684A1, Published 05/22/2020).
With regard to claims 1, 10, and 16-18, the reference teaches a composition comprising exosomes (extracellular vesicles, EVs) combined with a biocompatible collagen sheet for targeted delivery to musculoskeletal tissue, including repair of tendon injuries and ruptures, specifically Achilles tendon rupture (see, reference paragraphs [0039], [0068] and [0093]; claim 16; inter alia). A person of ordinary skill in the art would have recognized that selecting purified exosomes for therapeutic use in treating such injuries or ruptures would have been a predictable and routine modification. Accordingly, claims 1, 10, and 16-18 are rendered obvious over the reference.
With regard to claims 2-5, the reference teaches that the diameter of EVs may range from about 30 nm to about 200 nm (reference paragraph [0064]), which is less than 300 nm (as recited in instant claim 2) and encompass the claimed ranges of 20-200 nm (instant claims 3-5).
With regard to claims 6-7, the reference expressly teaches exosome marker CD63 (reference paragraphs [0015], [0074], and [0075]; FIG. 2C). Controlling the concentration and selection of CD63- versus CD63+ exosomes is routine optimization once the targeted marker is recognized and investigated, as evidenced by FIG. 2C. Accordingly, claims 6-7 are obvious over the reference.
With regard to claims 11, which depends from claim 10, and ultimately from claim 1, the reference teaches a biocompatible collagen sheet to facilitate tendon repair and rupture healing (reference claim 7, inter alia). A person of ordinary skill in the art would have been motivated to select type I fibrillar collagen, a well-characterized and commonly used collagen type for musculoskeletal and tendon scaffolds, to provide predictable structural support and promote regenerative outcomes in tendon rupture. Accordingly, claim 11 is obvious over the reference, as the selection of type I fibrillar collagen constitutes routine optimization of known scaffold material for tendon repair and rupture treatment.
With regard to claims 12-15, the reference teaches compositions for tissue or tendon repair applied directly to the injured tissue (reference paragraphs [009], [0020], [0024], [0025], [0027]-[0036]; claim 11, inter alia) and teaches experimentation under various conditions, including as a function of time, to evaluate outcomes and effectiveness. Based on these teachings, the claimed outcomes of decreasing adhesion formation (instant claim 13), increasing type I to type III collagen ratio (instant claim 14), and achieving more organized collagen architecture (instant claim 15) would have been predictable biological effects resulting from the application of regenerative exosome compositions to injured tendon tissue. Accordingly, claims 12-15 are obvious over the reference.
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.
[5] Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of co-pending application No. 18/714438 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because co-pending application No. 18/714438 teaches a composition comprising purified exosome product (PEP) (reference claim 1); and a pharmaceutically acceptable carrier (reference claim 1) comprising a supportive matrix (reference claim 10), wherein the supportive matrix comprises a collagen scaffold (reference claim 11), corresponding to instant claims 1 and 10.
Claim 1 of the reference is directed to a method; however, it expressly teaches a PEP composition. The dependent claims of the reference further define compositional features that correspond directly to the composition disclosed in the instant claims.
The co-pending application further teaches claims 2-9 that correspond one-to-one, in identical numerical order, with instant claims 2-9. Each of these reference claims is not patentably distinct from the identically numbered instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
[6] Claims 1, 2, and 5-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-11 of co-pending application No. 18/709931 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because co-pending application No. 18/709931 teaches a composition comprising purified exosome product (PEP) (reference claim 1); and a pharmaceutically acceptable carrier (reference claim 1) comprising a supportive matrix (reference claim 10), wherein the supportive matrix comprises a collagen scaffold (reference claim 11), corresponding to instant claims 1 and 10.
Claim 1 of the reference is directed to a method; however, it expressly teaches a PEP composition. The dependent claims of the reference further define compositional features that correspond directly to the composition disclosed in the instant claims.
Reference claims 3 and 5 teaches that the PEP comprises spherical or spheroid exosomes having a diameter of 56-151 nm and 43-151 nm, respectively, which encompass the limitation of instant claim 5, wherein the PEP comprises spherical or spheroid exosomes having a mean diameter of 110 nm ± 30 nm (80-140 nm).
The co-pending application further teaches claims 2 and 6-9, which corresponds one-to-one, in identical numerical order, with instant claims 2 and 6-9. Each reference claim is not patentably distinct the identically numbered instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
[7] Claims 1-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of co-pending application No. 18/248615 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because co-pending application No. 18/248615 teaches a composition comprising purified exosome product (PEP) (reference claim 1) and a pharmaceutically acceptable carrier (reference claim 1) comprising a supportive matrix (i.e., a surgical glue or tissue adhesive) (reference claim 1) (the carrier in a surgical setting may be a surgical glue, a tissue adhesive, and/or a supportive matrix; instant application, page 10, lines 23-27), corresponding to instant claim 1.
The co-pending application further teaches claims 2-9, which correspond one-to-one, in identical numerical order, with instant claims 2-9. Each of these reference claims is not patentably distinct from the identically numbered instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
[8] Claims 1-2 and 6-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 9-10, and 51 of U.S. Patent No. US20210169812A1. Although the claims at issue are not identical, they are not patentably distinct from each other because U.S. Patent No. US20210169812A1 teaches a composition comprising purified exosome product (PEP) (reference claim 9) and acceptable carrier comprising a supportive matrix (i.e., biocompatible matrix) (reference claim 9), wherein the supportive matrix comprises a collagen (reference claim 10) (i.e., collagen scaffold, see reference paragraphs [0021], [0030], and [0077]), corresponding to instant claims 1 and 10.
The co-pending application further teaches claims that correspond directly to the instant claims. In particular, reference claims 1, 4, and 5 align respectively with instant claims 2, 6, and 7. Each of these reference claims is not patentably distinct from the corresponding instant claims.
The co-pending application teaches that the PEP comprising at least 1 × 1010 exosomes/mL (reference claim 51), corresponding to the concentration ranges disclosed in instant claims 8 and 9. Instant claims 8 requires 1 x 1011 PEP to 1 x 1013 PEP exosomes, and instant claim 9 narrows this range to 1 X 1012 to 1 x 1013 PEP exosomes. Accordingly, the claimed concentration ranges are not patentably distinct from the co-pending reference.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALI M ALAOUIE whose telephone number is 571-272-0844. The examiner can normally be reached Flextime: (M-TH) 7:30 am 6:30 pm.
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/ALI M. ALAOUIE/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614