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 .
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.
Claim Status
Claims 1-7, 15, 54, 56, 59, 62, 65-67, 69, 72-74, 77 are currently pending and examined on the merits.
Claim Interpretation
Claims 74, 77 contain the claim limitation “optionally”. These limitations are not considered to be required limitations of the claim and are not considered in the patentability analysis.
Claim Objections
Claims 65-66 are objected to because of the following informalities. Appropriate correction is required.
Claim 65 appears to be missing a comma, and should read “EG-VEGF, or any combination thereof”.
Claim 66 appears to be missing a comma, and should read “conditioned medium, or in a reprogramming medium”.
Claim Rejections - 35 USC § 112
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 1-7, 15, 54, 56, 59, 62, 65-67, 69, 72-74, 77 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.
Generally, when the claims are indefinite, vague or unclear, they cannot be construed without speculation or conjecture; therefore, the indefinite claims are not treated on the merits with respect to prior art. See In re Steele, 305 F.2d 859, 862 (CCPA 1962) (A prior art rejection cannot be sustained if the hypothetical person of ordinary skill in the art would have to make speculative assumptions concerning the meaning of claim language.); see also In re Wilson, 424 F.2d 1382, 1385 (CCPA 1970) ("If no reasonably definite meaning can be ascribed to certain terms in the claim, the subject matter does not become obvious-the claim becomes indefinite."). Notwithstanding Steele, the Office has made every attempt to construe the claims in what the Office believes is the intent of the Applicants in the interest of compact prosecution.
Claim 1 recites the limitation "said cell". There is insufficient antecedent basis for this limitation in the claim.
The term “suitable” in claim 2 is a relative term which renders the claim indefinite. The term “suitable” 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.
Claim 2 contains the limitation “a multiple cell suspension”. It is unclear if this limitation is indicating that there are multiple cells contained in suspension, or if the suspension contains cell aggregates.
Claim 3 contains the limitation “agents capable of augmenting production of neuronal regenerative properties”. See Application of Collier, 397 F.2d 1003 (C.C.P.A. 1968), which states claims are considered indefinite when “things which may be done are not required to be done". It is unclear whether augmentation of neuronal regenerative properties is a required limitation of the claim or merely optional.
Claim 3 contains the limitation “said cells”. It is unclear if this limitation is referring to the “said fibroblast cells” of claim 3 or the “said cell” of independent claim 1.
Claim 5 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 5 contains the limitation “wherein culturing of said fibroblasts occurs in a conditioned media” Claim 5 depends from claim 1, which contains no limitations directed to culturing.
Claim 15 recites the limitation "said fibroblasts" in the preamble. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said toll like receptor" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-1" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-2" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-3" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-4" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-5" in line 11. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-6" in line 12. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-7" in line 13. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-8" in line 14. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said agonist of TLR-9" in 16. There is insufficient antecedent basis for this limitation in the claim.
Claim 67 recites the limitation "the plurality". There is insufficient antecedent basis for this limitation in the claim.
Claim 69 contains the limitation “fibroblast cells culture”. It is unclear if this limitation is indicating that the supernatant is derived from multiple cell cultures of fibroblasts (i.e., a pooled supernatant) or a single culture of fibroblasts.
Claim 72 recites the limitation "the culturing" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 72 recites the limitation "said fibroblast or plurality thereof" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 72 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 5 contains the limitation “wherein the culturing of said fibroblast cell or plurality thereof” Claim 5 depends from claim 1, which contains no limitations directed to culturing.
Claim 73 recites the limitation "said plurality of fibroblast". There is insufficient antecedent basis for this limitation in the claim.
Claim 74 contains the limitation “a multiple cell suspension”. It is unclear if this limitation is indicating that there are multiple cells contained in suspension, or if the suspension contains cell aggregates.
Claim 77 contains the limitation “that allows proliferation of said fibroblasts”. See Application of Collier, 397 F.2d 1003 (C.C.P.A. 1968), which states claims are considered indefinite when “things which may be done are not required to be done". It is unclear whether proliferation is a required limitation of the claim or merely optional.
Claim 77 contains the limitation “extracting from multi cell suspension cells”. It is unclear if this limitation is indicating that there are multiple cells contained in suspension, or if the suspension contains cell aggregates. Further it is unclear what is extracted from the multi cell suspension cells
Claim 77 contains multiple uses of the limitation “said fibroblasts”. It is unclear to which population of fibroblasts these limitations are referring (e.g., the fibroblasts of the preamble or the fibroblasts produced by the preceding step.
Claim 77 recites the limitation "said cell" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 77 appears to contain duplicate limitations. It is unclear if these limitations are intended to be recited as alternatives, or if they are required limitations of the claim.
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.
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.
Claim(s) 1-2, 66, 54, 56, 74, 77 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ezquer et al., (2018) Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids reduces chronic alcohol intake and abolishes binge-drinking. Sci Rep 8, 4325 (cited on IDS dated 10/3/24, hereinafter Ezquer)., as evidenced by Oses et al., (2017) Preconditioning of adipose tissue-mesenchymal stem cells deferoxamine increases the production of pro-angiogenic neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy. PloS One 12, e0178011 (cited on IDS dated 10/3/24, hereinafter Oses)., and in view of Ichim et al., Fibroblasts as a practical alternative to mesenchymal stem cells. J Transl Med 16, 212 (2018) (cited on IDS dated 10/3/24, hereinafter Ichim).
Regarding claims 1, 74, Ezquer discloses methods of treating alcohol-use disorders by administering mesenchymal stem cells (MSCs) (Abstract). Ezquer explains that chronic alcohol consumption, and other addictive drugs, is associated with neuroinflammation (Introduction). Ezquer discloses administering adipose-derived MSC spheroids via intracerebroventricular or intravenous administration to a rat model of chronic alcohol consumption (Intracerebroventricular (ICV) administration of MSC-spheroids, Intravenous administration of MSC-spheroids). Ezquer discloses that the MSCs demonstrate the expression profile positive for CD29, CD13, CD105, CD73, CD90, and CD44, and negative expression of CD235a, CD45, and CD31 (MSCs cultured as 3D-spheroid structures increase their anti-inflammatory potential). Ezquer explains that administration of the MSC-spheroids significantly reduces alcohol-induced inflammation, normalizes oxidative stress in the hippocampus (i.e., damage in the hippocampus), normalizes ethanol-induced astrocyte changes, reduces voluntary alcohol intake (i.e., relapse), and reduces binge drinking (Discussion).
Regarding claims 2, 66, Ezquer discloses isolating adipose-derived MSCs, sorting via flow cytometry, and culturing in α-MEM supplemented with 10% fetal bovine serum (FBS) (Isolation, expansion and characterization of human adipose-derived mesenchymal stem cells (hAD-MSCs); citing to Oses). The MSCs are then cultured such that the form 3-dimensional (3D) spheroids (Generation and dissociation of MSC-spheroids).
Ezquer does not disclose that the cells are fibroblasts.
Ichim discloses that fibroblasts are a functional and practical alternative to MSCs (Abstract). Ichim explains that MSCs are relatively rare in tissues such that it is difficult to obtain therapeutically effective numbers of MSCs (Introduction). Fibroblasts are more easily obtained and have a shorter doubling time than MSCs (Introduction). Further fibroblasts demonstrate a similar expression profile to that of bone marrow-derived MSCs (positive expression of CD105, CD73, CD90, and negative expression of CD34, CD45), similar differentiation potential, and similar immune modulation properties (Mesenchymal properties of fibroblasts: differentiation, Mesenchymal properties of fibroblasts: immune modulation). Ichim concludes that allogenic fibroblasts may be a viable and practical alternative to MSCs for therapeutic applications (Conclusion). It would be obvious to one of ordinary skill in the art that the fibroblasts of Ichim could be substitutes for the MSCs of Ezquer are suggested by Ichim. A skilled artisan would be motivated to substitute the fibroblasts to more easily acquire therapeutic numbers of fibroblasts.
Regarding claims 54, 74, 77, the combination of Ezquer and Ichim does not disclose that the addiction is an opioid or heroin addiction. However, Ezquer explains that neuroinflammation is also associated with the chronic use of addictive drugs including cocaine, opiates (e.g., heroin), marijuana, and methamphetamines (Introduction). Thus, there is a suggestion present in Ezquer that the disclosed methods would likewise be effective for the treatment of an opiate or heroin addiction.
Regarding claim 56, the combination of Ezquer and Ichim does not disclose that the fibroblasts are autologous to the subject being treated. However, cell-based therapeutics may be only one of three options, xenogeneic, allogeneic, or autologous. It would be obvious to one of ordinary skill in the art to try using autologous cells as one of three know cell sources with a reasonable expectation of successfully treating the subject.
Claim(s) 3-7, 65, 69, 72, is/are rejected under 35 U.S.C. 103 as being unpatentable over Ezquer in view of Ichim as applied to claims 1-2, 66, 54, 56, 74, 77 above, and in further view of Oses.
Regarding claim 3, 65, 72, the combination of Ezquer and Ichim does not disclose that the fibroblasts are primed with an agent that augments production of neuronal regenerative properties.
Oses discloses methods of preconditioning MSCs with deferoxamine (DFX) (Abstract). Oses discloses isolating adipose-derived MSCs, sorting via flow cytometry, and culturing in α-MEM supplemented with 10% fetal bovine serum (FBS) (Isolation, expansion and characterization of human AD-MSCs). Passage 3 MSCs are incubated in α-MEM without FBS, and with DFX for 48 hours (MSC preconditioning with DFX and determination of cell viability). Oses explains that preconditioning with DFX increases the expression and secretion of pro-angiogenic, neuroprotective, and anti-inflammatory factors, such as angiopoietin 1, VEGF, bFGF, and PDGF (Deferoxamine preconditioning increases the expression and secretion of pro-angiogenic, neuroprotective, and anti-inflammatory factors). The preconditioned MSCs further demonstrate neuroprotective and anti-inflammatory effects (Discussion, Conclusion).
As Ezquer cites to Oses for methods of processing MSCs it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to combine the references to further improve the neuroprotective and anti-inflammatory effects of the cells.
Regarding claims 4, the combination of Ezquer, Ichim, and Oses does not disclose that the priming agent is angiopoietin-1. However, Oses explains that preconditioning with DFX resulted in a significant increase in the expression and secretion of angiopoietin-1 (Deferoxamine preconditioning increases the expression and secretion of pro=angiogenic, neuroprotective and anti-inflammatory factors). Oses attributes the improved neuroprotective and anti-inflammatory, at least in part, to this increase in secretion of angiopoietin-1. Thus, there is a suggestion present in Oses that angiopoietin-1, alone or in combination with other factors, could improve neuroprotective and anti-inflammatory in cells preconditioned with angiopoietin-1.
Regarding claim 6-7, the claims recite the intended result of the method rather than requiring an additional, active method step be performed. MPEP § 2111.04 states “[c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since these claims only recite the results of the actively recited method steps (resultant neuronal regenerative properties), art reading on the method of claim 3, necessarily results in the potential to augment neuronal regenerative properties in the absence of evidence to the contrary.
Regarding claims 5, 69, Oses discloses that following incubation of the MSCs with DFX, the culture media is collected and purified to produce a secretome product (Purification of secretome). Incubation with DFX results in a significant increase in VEGF-A and IL-4 (Deferoxamine preconditioning increases the expression and secretion of pro-angiogenic, neuroprotective and anti-inflammatory factors, Fig. 4). Oses further discloses that DRG neurons treated with the DFX treated MSC secretome demonstrate a neuroprotective effect (The secretomes of DFX preconditioned MSCs reduce glucose-induced DRG neuron death).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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