DETAILED ACTION
Applicant’s response filed 4/3/2026 has been received and entered into the application file. All arguments have been fully considered. Claims 46 and 142-160 are currently pending. Claims 1-45 and 47-141 are cancelled. Claim 46 is amended. Claims 142-160 are new.
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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4/3/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings- Objection Withdrawn
The corrected drawing sheets are in compliance with 37 CFR 1.121(d). Therefore, the objection to the drawings is withdrawn.
REJECTION(S) WITHDRAWN
Claim Rejections - 35 USC § 102
RE: Rejection of Claims 42, 46, 52 and 55 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Yivgi-Ohana:
Applicant’s amendment submitted 4/3/2026 has cancelled claims 42, 52 and 55.
Applicant’s amendment submitted 4/3/2026 now requires a method of enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated, modified chondrisomes derived from blood or a blood product.
Yivgi-Ohana do not further teach enhancing uncoupled respiration, therefore the previous rejection is withdrawn.
Double Patenting
RE: Rejection of Claims 46, 52 and 55 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-23 of U.S. Patent No. 11,903,974;
Rejection of Claims 46, 52 and 55 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 19-21 of U.S. Patent No. 11,903,975;
Rejection of Claims 42, 46, 52 and 55 on the ground of nonstatutory double patenting as being unpatentable over claims 7, 42, 46 and 52 of copending Application No. 17/651,056;
Rejection of Claims 42, 46, 52 and 55 on the ground of nonstatutory double patenting as being unpatentable over claims 7, 42, 46 and 52 of copending Application No. 18/403,586:
Rejections are withdrawn in view of Applicant’s amendment submitted 4/3/2026 which now requires a method of enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated, modified chondrisomes derived from blood or a blood product.
NEW GROUND(S) OF REJECTION, NECESSITATED BY AMENDMENT
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 46 and 142-160 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 46 has been amended to recite the following:
46. A method of enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated, modified chondrisomes derived from blood or a blood product.
Dependent claims 142-160 either depend directly from claim 46, or incorporate the method of claim 46.
Claim 142 recites limitations directed to the process employed for isolating chondrisomes, however the recited separating and centrifugation steps are generically recited and do not include any specificity as to the parameters (centrifugation speed, requirement for density gradient) required for removing blood cells that do not comprise chondrisomes from blood cells that comprise chondriosomes.
Claim 159 encompasses limitations that the isolated chondrisomes express uncoupling proteins selected from UCP-1, UCP-2, UCP-3, UCP-4 or UCP-5.
Upon further review of the specification, in view of the newly amended claim limitations, the specification shows that Applicants have not provided sufficient description of the invention to support they were in possession of enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated chondrisomes derived from any portion of blood or any blood product, and expressing uncoupling proteins UCP-1, UCP-2, UCP-3, UCP-4 or UCP-5.
In the instant case the only reference in the specification to enhancing uncoupled respiration in a target cell or tissue, is set forth at Example F-11 and is directed to chondrisome preparations that were generated from mouse brown adipose tissue (BAT), wherein HEPG2 cells were treated with 4-90 grams of BAT chondrisome protein per 100,000 cells and the cells were incubated with chondrisomes for 48 hours and thereafter oxygen consumption rates of HEPG2 cells were measured by XF96 bioenergetic assay (Agilent). Treated HEPG2 cells were shown to have an increase in the uncoupled respiration ratio of 10-30% over untreated cells, see Figure 3.
A review of the specification does not further disclose isolation of chondriosomes from all types of blood products, including from erythrocytes, and thereafter delivering erythrocyte-isolated chondrisomes to target cells or tissues, as currently claimed. Thus, a review of the specification shows that Applicants have not provided sufficient description of the invention to support they were in possession of enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated, modified chondrisomes derived from any component of blood or any blood product.
Further regarding isolation of chondriosomes (mitochondria) from blood or a blood product, it is noted this limitation encompasses any fraction of whole blood, e.g., mature erythrocytes (red blood cells), that would not comprise mitochondria (chondrisomes) and thus do not comprise native uncoupling proteins.
Lin et al (see PTO-892) evidences that mitochondria are absent from red blood cells (Abstract). The Human Protein Atlas evidences that UCP1 protein was not detected in blood e.g., erythrocytes. Flachs et al., (FEBS 2007; see PTO-892) further evidences that mitochondrial uncoupling protein 2 (UCP2) is abundant in developing monocyte/macrophage cells (Abstract), however, UCP2 is not present in mature erythrocytes (Fig 3B). Thus, the specification has not provided sufficient description of the invention to support isolation of chondriosomes (mitochondria) from the generically recited blood or blood products, which encompass blood components, e.g., red blood cells that do not appear to comprise mitochondria The claims are not limited to the scope of blood cells that would comprise uncoupling proteins for enhancing uncoupled respiration.
Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 USC 112, first paragraph.
Enablement:
Claims 46 and 142-160 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for enhancing uncoupled respiration in a target cell or tissue comprising delivering to the target cell or tissue a pharmaceutical composition comprising chondrisomes, or comprising a chondrisome preparation comprising isolated chondriosomes, wherein the chondrisomes are derived from brown adipose tissue, or derived from chondrisome-containing blood cells or derived from other chondrisome-containing cells, does not reasonably provide enablement for the invention as currently claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As set forth above, claim 46 recites the following:
46. A method of enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated, modified chondrisomes derived from blood or a blood product.
Dependent claims 142-160 either depend directly from claim 46, or incorporate the method of claim 46.
Claim 159 encompasses limitations that the isolated chondrisomes express uncoupling proteins selected from UCP-1, UCP-2, UCP-3, UCP-4 or UCP-5.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill:
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples;
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of the claims:
With respect to the breadth of the claims, the claims as currently drafted encompass a method for enhancing uncoupled respiration in a target cell or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated chondrisomes derived from any portion of blood or any blood product (claims 46 and 142), and expressing uncoupling proteins UCP-1, UCP-2, UCP-3, UCP-4 or UCP-5 (claim 159).
Consequently, the breadth of the claims includes isolating chondrisomes from blood cell types that do not comprise chondrisomes (mitochondria), or comprise uncoupling proteins UCP-1, UCP-2, UCP-3, UCP-4 or UCP-5.
Nature of the invention:
The invention is in the field of cell biology.
The state of the prior art and predictability in the art: With respect to the state of the prior art, and predictability of the art, at the time of filing the instant invention methods of delivering mitochondria (chondrisomes) was known for significantly increasing ATP levels in target cells, thus enhancing the function of target cells, as taught by previously cited Yivgi-Ohana. However, the prior art does not further teach methods for enhancing uncoupled respiration in target cells or tissue, comprising delivering to the target cell or tissue a pharmaceutical composition or chondrisome preparation comprising isolated chondrisomes derived from any type of blood cell, such as erythrocytes that do not comprise mitochondria.
As set forth above, Lin et al (see PTO-892) evidences that mitochondria are absent from red blood cells (Abstract). The Human Protein Atlas evidences that UCP1 protein was not detected in blood e.g., erythrocytes. Flachs et al., (FEBS 2007; see PTO-892) further evidences that mitochondrial uncoupling protein 2 (UCP2) is abundant in developing monocyte/macrophage cells (Abstract), however, UCP2 is not present in mature erythrocytes (Fig 3B). Thus, the skilled artisan would view the claimed method of enhancing uncoupled respiration in a target cell or tissue, wherein the method delivers chondrisomes derived from any blood component or any blood product, including erythrocytes, as highly unlikely since it is known that not all blood components or all fractions of blood comprise cells having chondrisomes.
Guidance of the Specification/Workinq Examples: Applicants have not provided any working examples showing isolation of chondrisomes from erythrocytes, and thereafter delivering the erythrocyte-derived chondrisomes to the target cells or tissues resulting in enhanced uncoupled respiration. In the instant case the only reference in the specification to enhancing uncoupled respiration in a target cell or tissue, is set forth at Example F-11 and is directed to chondrisome preparations that were generated from mouse brown adipose tissue (BAT), wherein HEPG2 cells were treated with 4-90 grams of BAT chondrisome protein per 100,000 cells and the cells were incubated with chondrisomes for 48 hours and thereafter oxygen consumption rates of HEPG2 cells were measured by XF96 bioenergetic assay (Agilent). Treated HEPG2 cells were shown to have an increase in the uncoupled respiration ratio of 10-30% over untreated cells, see Figure 3.
While lack of a working embodiment cannot be a sole factor in determining enablement, the absence of substantial evidence provides additional weight to the lack of enablement in consideration of the Wands factors as a whole.
The Quantitation of Experimentation Required: Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the expansive breadth of the blood components recited in the claims, the state of the prior art and its lack of predictability, and the complete lack of guidance in the form of working examples in the specification.
MPEP §2164.01(a), provides that “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 46 and 142-160, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 46 and 142-160 would not be enabled by the written disclosure. Therefore, claims 46 and 142-160 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to make the invention commensurate in scope with the claims.
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 145-152 and 155 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 145 recites the phrase “wherein the uncoupled respiration in the target cell or tissue is enhanced by at least 5%.”
The term “enhanced” is a relative term which renders the claim indefinite. The term “enhanced” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not understand the metes and bounds of the term “enhanced by at least 5%” since it is unclear as to what parameter the enhancement is related to. There is no indication as to any minimal/baseline/control parameter for determining “enhanced by at least 5%”.
Claim 146 recites the phrase “wherein the method reduces reductive stress in a target cell or tissue.”
The term “reduces” is a relative term which renders the claim indefinite. The term “reduces” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not understand the metes and bounds of the term “reduces” since there is no indication as to any minimal/baseline/control parameter, such as reduces reductive stress in a target cell or tissue as compared to cells or tissue that do not receive the chondrisome composition.
Claims 147, 148, 149 likewise recite the phrases “reduced by at least 5%”, “decreases reactive oxygen species (ROS) in the target cell or tissue”, and “decreased by at least 5%”, respectively.
As discussed above regarding claim 146, these limitations are relative terms which render the claims indefinite. The term “reduced”, “decreases” and “decreased” are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not understand the metes and bounds of the terms “reduced”, “decreases” and “decreased” since there is no indication as to any minimal/baseline/control parameter.
Claims 150-152 recite the phrases “increases thermogenesis in the target cell or tissue”, “thermogenesis in the target cell or tissue is increased by at least 5%”, and “further increases differentiation…”, respectively.
The terms “increases” and “increased” are relative terms which renders the claims indefinite. The terms are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not understand the metes and bounds of the terms “increases” and “increased” since there is no indication as to any minimal/baseline/control parameter.
Regarding claim 155, it is noted the claim recites the phrases “…e.g., an organ to be transplanted into a human…” and “e.g., a human heart, liver, lung, kidney, pancreas, intestine, thymus, eye…”, which are interpreted as exemplary language, thus said limitations render the claim indefinite because it is unclear whether the limitations following the “e.g.,” phrase are part of the claimed invention. See MPEP § 2173.05(d).
Response to Remarks
As set forth above the Double Patenting rejections and the rejection under 35 USC 102 have been withdrawn in view of Applicant’s amendment. However, Applicant’s amendment has necessitated new grounds of rejection under 35 USC 112 for the reasons discussed above.
Conclusion
No claim is allowed.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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