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 .
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/US21/60475, filed
23 November 2021. Acknowledgment is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 63117360, filed 23 November 2020.
Election/Restrictions
Applicant’s election without traverse of Group II, encompassing claims 92-104, and exosomes as the species of extracellular vesicles in the reply filed on 04 November 2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. Accordingly, claims 83-91 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 83-104, of record 04 November 2025, are pending. Claims 83-91 are withdrawn for reading on a non-elected invention. Prosecution on the merits commences for claims 92-104.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains a “Sequence Listing as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3)), but fails to comply with the requirements of 37 CFR 1.821 - 1.825 because a copy of the "Sequence Listing" in computer readable form (CRF) has not been submitted as required by 37 CFR 1.821(e)(1)(i) or 1.821(e)(2)(i) as indicated in item 2) above.
Required response - Applicant must provide:
A new CRF of the “Sequence Listing” in accordance with 37 CFR 1.821(e)(1)(i) or 1.821(e)(2)(i) and
A statement that the content of the CRF is identical of the “Sequence Listing” part of the disclosure, submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
Specification
The substitute Specification filed 21 November 2023 is acknowledged and entered into the application file.
With that, the substitute Specification is objected to for referencing colors within the figures, when colored drawings have not submitted in the application. More specifically, the Specification references colors at least within Page 22 in reference to Figure 2A. Applicant is requested to review the Specification to identify any additional references to colors within the drawings and delete as appropriate since black and white drawings are submitted. The Specification must be amended to delete reference to specific colors within the text of the Specification.
Appropriate correction is required.
Claim Objections
Claims 92 and 99 are objected to because of the following informalities:
Regarding claim 92: The instant claim is objected to for comprising an extraneous space between “EV” and “s” in the acronym “CDC-EVs” in Line 3.
Appropriate correction is required.
Regarding claim 99: The instant claim is objected to for reciting “… wherein the trauma results from gunshot or explosion” instead of “… wherein the trauma results from a gunshot or an explosion”, or the like.
Appropriate correction is required.
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.
(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 92-98 and 100-101 are rejected under 35 USC 102(a)(1) and 35 USC 102(a)(2) as being anticipated by Marbán et al (US 2020/0024604 A1).
Marbán et al has a publication date of 23 January 2020. It is of note that Marbán et al as cited (Eduardo Marbán) is not the same inventive entity/inventor of the current application (Linda S. Marban).
Regarding claims 92-93: Marbán et al disclose methods of repairing and/or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes (Abstract).
As such, Marbán et al disclose methods of treating acute traumatic injuries and shock, wherein a therapeutically effective amount of exosomes isolated from regenerative cells is administered to a mammalian subject in need thereof (Paragraphs [0010], [0060]-[0061], [0063]-[0064], [0071], [0079], [0086]-[0092]).
Marbán et al further disclose that the exosomes are isolated from cardiosphere-derived cells (CDC) (claim 93) (Paragraphs [0009], [0020], [0064], [0081]-[0083], [0086]-[0092]).
This therefore reads on the method of instant claim 92. See MPEP § 2112 and 2112.02.
Regarding claim 94: Following the discussion of claim 92, Marbán et al further disclose that the exosomes are derived from an autologous source with respect to the eventual recipient of the exosomes, wherein the exosomes are derived from humans (Paragraphs [0007], [0026], [0065]). This therefore reads on the method of the instant claim.
Regarding claims 95-97: Following the discussion of claim 92, Marbán et al further disclose that the acute traumatic injury includes a crush or compression injury in the CNS, including a crush or compression injury of the brain (claims 96-97), spinal cord, nerves, and/or retina (claim 95) (Paragraphs [0010], [0074]-[0077]). This therefore reads on the method of the instant claims.
Regarding claim 98: Following the discussion of claim 96, Marbán et al further disclose that the CDC-exosomes can be administered to the subject to treat damaged skeletal muscle tissue or skeletal bone cells (Paragraphs [0010], [0077]). Although Marbán et al do not explicitly disclose that the damaged skeletal cells have undergone trauma, the ordinary artisan would have recognized that the CDC-exosomal treatment can readily administered to traumatically damaged skeletal cells with predictable results since the disclosure of Marbán et al teach the administration of CDC-exosomes for (i) the treatment of acute traumatic injuries, and (ii) the treatment of skeletal bone cells. See MPEP § 2143(I)(A). This therefore renders obvious the method of the instant claim.
Regarding claim 100: Following the discussion of claim 92, Marbán et al further disclose that the CDC-exosomes are administered within about 1 to about 2 hours following the traumatic injury (Paragraph [0072]). This therefore reads on the method of the instant claim. See MPEP § 2131.03.
Regarding claim 101: Following the discussion of claim 92, Marbán et al further disclose that the administration of CDC-exosomes to a subject reduces the mortality of the subject when compared to subjects that have not received CDC-exosomes (Paragraph [0086]; Figure 9). This therefore reads on the method of the instant claim.
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.
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 92-99, 100-101, and 103-104 are rejected under 35 U.S.C. 103 as being unpatentable over Marbán et al (US 2020/0024604 A1) in view of Liu (WO 2019/165267 A1).
The discussion of Marbán et al regarding instant claim 92 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Marbán et al anticipate claims 92-98 and 100-101. Liu is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 29 August 2019.
Regarding claims 99 and 103-104: Following the discussion of claim 92 above, Marbán et al further disclose that the acute traumatic injury includes a crush or compression injury in the CNS, including a crush or compression injury of the brain, spinal cord, nerves, and/or retina (Paragraphs [0010], [0074]-[0077]).
Marbán et al further disclose that microRNAs can be comprised within the CDC-exosomes, including miR-125b (Paragraphs [0015]-[0017], [0078]).
Marbán et al do not disclose that the acute traumatic injury is from a gunshot or an explosion, as required by instant claim 99.
Liu, however, discloses the treatment of acute traumatic brain injuries, wherein subjects suffering from a traumatic brain injury are administered miR-125b comprised within an exosome (Abstract; Paragraphs [0008], [0014], [0082], [0087]-[0088]). Liu further discloses that the acute traumatic brain injury is result of a gunshot wound and/or combat injury (Paragraphs [0030], [0077]).
Therefore, it would have been prima facie obvious to have modified the treatment method of Marbán et al such that the CDC-exosomes are administered to a subject suffering from a traumatic gunshot wound or combat injury, as detailed in Liu. One of ordinary skill before the effective filing date of the invention would have been motivated to treat a variety of acute traumatic brain injuries, and would have had a reasonable expectation of success given that the disclosures of both Marbán et al and Liu are concerned with the treatment of acute traumatic injuries of the brain via the administration of exosomal-packaged miR-125b. See MPEP § 2143(I)(G).
Consequently, Marbán et al as modified by Liu render obvious a method of treating shock resulting from an acute traumatic injury comprising the administration of a therapeutically effective amount of CDC-exosomes to the subject, wherein the acute traumatic injury is a gunshot wound (claim 99) and/or combat injury (claim 104). Given that the treatment method addresses combat injuries, the ordinary artisan also would have recognized that the subject can be a military personnel (claim 103). This therefore renders obvious the method of the instant claims.
Claims 92-98 and 100-102 are rejected under 35 U.S.C. 103 as being unpatentable over Marbán et al (US 2020/0024604 A1, hereinafter referred to as Marbán ‘604) in view of Marbán et al (WO 2019/152549 A1, hereinafter referred to as Marbán ‘549, of record on the IDS filed 31 December 2025).
The discussion of Marbán ‘604 regarding instant claim 92 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Marbán ‘604 anticipate claims 92-98 and 100-101. Marbán ‘549 is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 08 August 2019. It is of note that Marbán ‘549 as cited (Eduardo Marbán) is not the same inventive entity/inventor of the current application (Linda S. Marban).
Regarding claim 102: Following the discussion of claim 92 above, Marbán ‘604 further disclose that the CDC-exosomes can be administered to treat kidney cells (Paragraph [0077]).
Marbán ‘604 do not disclose that the administration of CDC-exosomes reduced the serum levels of lactate, glucose, or creatinine within the subject, as required by instant claim 102.
Marbán ‘549, however, disclose the administration of CDC-exosomes for the treatment of damaged kidneys (Paragraphs [0007], [0016], [0055], [0085], [0087]-[0088], [0094]-[0095], [0106]). Marbán ‘549 further discloses that kidney dysfunction is determined by increased or excessive creatinine levels in the subject’s blood, plasma, or serum, wherein treatment with the CDC-exosomes decreases the extent of the injury – or dysfunction – within the kidney (Paragraph [0094]).
Therefore, it would have been prima facie obvious to have modified the treatment method of Marbán ‘604 such that the administration of CDC-exosomes reduces the creatinine levels within the serum of a subject suffering from a traumatic kidney injury, as detailed in Marbán ‘549. One of ordinary skill before the effective filing date of the invention would have been motivated to lower the serum creatinine levels within a subject, as that is an indicator that the kidney dysfunction is being reversed, and would have had a reasonable expectation of success given that the disclosures of both Marbán ‘604 and Marbán ‘549 are concerned with the treatment of acute traumatic injuries of the kidney via the administration of CDC-exosomes. See MPEP § 2143(I)(G).
Consequently, Marbán ‘604 as modified by Marbán ‘549 render obvious a method of treating shock resulting from an acute traumatic kidney injury comprising the administration of a therapeutically effective amount of CDC-exosomes to the subject, wherein the administration results in a decrease of serum creatinine levels. This therefore renders obvious the method of the instant claim.
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 92-104 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 10,695,293 B2 in view of Marbán et al (US 2020/0024604 A1, hereinafter referred to as Marbán ‘604), Liu (WO 2019/165267 A1), and Marbán et al (WO 2019/152549 A1, hereinafter referred to as Marbán ‘549, of record on the IDS filed 31 December 2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims. More specifically, the patented claims are not identical because no single patented claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patent claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a method of preventing or treating cutaneous injury in a subject in need thereof, the method comprising administrating to the subject a therapeutically or prophylactically effective dose of extracellular vesicles, wherein said extracellular vesicles are obtained from cardiospheres or cardiosphere-derived cells (CDCs), or from newt A1 cell line.
Patent claim 1 does not teach that the CDC-extracellular vesicles are administered for the treatment of shock subsequent to trauma and hemorrhage, as required by instant claim 1.
Marbán ‘604, however, disclose methods of treating acute traumatic injuries and shock, wherein a therapeutically effective amount of exosomes isolated from regenerative cells is administered to a mammalian subject in need thereof (Paragraphs [0010], [0071], [0079], [0086]-[0092]). Marbán ‘604 further disclose that the acute traumatic injury includes the laceration of skin cells (Paragraphs [0010], [0074], [0077]).
Marbán ‘604 further disclose that the exosomes are isolated from cardiosphere-derived cells (CDC) (Paragraphs [0009], [0020], [0064], [0081]-[0083], [0086]-[0092]).
Therefore, it would have been prima facie obvious to have modified the treatment method of the patented claims such that the treatment of a cutaneous injury also involves the treatment of post-injury shock, as detailed in Marbán ‘604. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to also treat the secondary effects of acute cutaneous injuries, and would have had a reasonable expectation of success given that the patent claims and disclosure of Marbán ‘604 are both concerned with the treatment of acute injuries via the administration of CDC-extracellular vesicles.
Consequently, patent claim 1 in view of Marbán ‘604 render obvious a method of treating shock subsequent to an acute traumatic cutaneous injury in a subject, wherein a therapeutically effective amount of CDC-extracellular vesicles is administered to the subject. This therefore renders obvious the method of instant claim 92.
Patent claim 8 further limits the method of patent claim 1, wherein the extracellular vesicles are exosomes. This therefore reads on the method of instant claim 93.
With that, instant claims 94-104 are known from the prior art and can be further incorporated into the method rendered obvious by patent claims 1 as modified by Marbán ‘604:
Marbán ‘604 teach the limitations of instant claims 94-98 and 100-101.
Liu teaches the limitations of instant claims 99 and 103-104.
Marbán ‘549 teach the limitation of instant claim 102.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can
normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633