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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claim Objections
Claims 2 and 16 are objected to because of the following informalities: expansion of RNAK in line 2, is required. Further claim 16 recites "The method of claims 1," which is grammatically incorrect. The claim needs to recite "The method of claim 1." Appropriate correction is required.
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 2-3, 12-14, and 19 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.
The term “low planetary orbit” in claim 2 is unclear, as it is not clear as to which planet is referred in the claim. It is noted that some planets have higher gravitational forces and the gravitational forces for that planet may be higher than 1g. Appropriate clarification is required. It is also submitted that the term “low” in claims 2 and 3, as applied to planetary orbit, low Earth orbit, low Moon orbit and low Mars orbit is a relative term which renders the claim indefinite. The term “low” 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.
Claims 12 requires a reprogrammed cell (See line 1). It is noted that the claim is indirectly dependent on claim 1 and directly dependent on claim 9. However, it is submitted that reprogrammed cells have no antecedent basis.
Claim 13 requires “said DNA demethylating agent” and refers back to claim 12 which requires a DNA methyltransferase inhibitor. It is submitted that DNA demethylating agent does not have an antecedent basis.
Claim 17 requires a bone targeting technology for which there is no antecedent basis.
Claim 19 recites “solar particle events” in parentheses. The metes and bounds of this phrase are indefinite since it is unclear how these limitations relate to the scope of the claimed invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 15 is directed towards the use of antioxidants, but the claim does not further limit the method of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Regarding claims 1-20: The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant's specification is not found to be enabling for use of stem cells for treatment of bone-loss due to microgravity in any dosage, using any administration route, with or without the antioxidants and/or NF-kappa B inhibitors at any dosage and at any point of time. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to carry out the method of the invention commensurate in scope with the current claims.
Analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue or unreasonable experimentation. See Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916). The key word is 'undue,' not experimentation.' " (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Applicants' claims are directed to delivery of any use of stem cells for “prevention” of bone-loss due to microgravity in any dosage, using any administration route, with or without antioxidants and/or NF-kappa B inhibitors at any dosage and at any point of time. The breadth of the claims includes a method of treating microgravity induced bone loss using any stem cell, at any dosage, with or without antioxidants and/or NF-kappa B inhibitors at any dosage and at any point of time before, with or after administration of stem cells.
The specification indicates that stem cells can be administered by localized injection (e.g., catheter administration or direct intra-bone injection), systemic injection, intravenous injection, intrauterine injection, and parenteral administration, among others. (See specification [0137]). Further the specification indicates that stem cells can be embryonic stem cells, cord blood stem cells, placental stem cells, bone marrow stem cells, amniotic fluid stem cells, neuronal stem cells, circulating peripheral blood stem cells, mesenchymal stem cells, germinal stem cells, adipose tissue derived stem cells, exfoliated teeth derived stem cells, hair follicle stem cells, dermal stem cells, parthenogenically derived stem cells, reprogrammed stem cells and side population stem cells. (See specification [0138]). Further the specification provides a list of different antioxidants ([0147]) and NF-KB inhibitors ([0121]). At the time the invention was filed it was known that although use of mesenchymal stromal cells (MSCs) was explored for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. (See Levy et al Sci Adv. 2020 Jul 22 Abstract; PTO-892). It was known that several factors that likely contribute to their suboptimal clinical outcomes, including heterogeneity in the potency of the MSC product, variable biodistribution and pharmacokinetics with different administration routes, and a limited understanding of the impact the host response has on therapeutic efficacy after administration. Therefore, there was a recognized level of unpredictability with regards to generation and delivery of stem cells and their use for treatments for various ailments.
Due to the lack of teachings in the art regarding specific formulation and guidance regarding their delivery, combinations with appropriate dosages of antioxidants/or other modulators such as NF-kB inhibitors and the recognized unpredictability in the area of cell-based therapeutics, a large amount of guidance and teachings would be necessary in order to be enabling for methods of such.
There is no guidance and teachings provided by Applicants in the instant specification regarding use of stem cells for treatment of microgravity induced bone loss. The Examiner acknowledges that the Office does not require the presence of working examples to be present in the disclosure of the invention (see MPEP §2164.02). However, in light of the state of the art, discussed above, which recognizes a high level of unpredictability in the field of use of stem cells for treatment of various ailments, the Office would require appropriate disclosure to support a method of delivery of NF-kappa B inhibitors using quantum dots. The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Thus, due to the high level of unpredictability in the art, the current specification would have to provide greater amounts of teachings and guidance directed to methods of carrying out the claimed invention.
Therefore, due to the sum of all the aforementioned factors, one of ordinary skill in the art, at the time the invention was made, would not expect success carrying out the claimed method of bone targeting using any stem cell with or without antioxidants and/or other modulators. Given that the art fails to recognize and Applicant has failed to demonstrate the claimed method, the skilled artisan would be faced with the impermissible burden of undue experimentation in order to practice the claimed invention. Accordingly, claims 1-20 are deemed properly rejected.
Prevention of bone density loss:
The claims are drawn to a method for preventing bone density loss
The person of ordinary skill in the art would not have had a reasonable expectation for successfully preventing bone density loss. Prevention of bone density loss, for the purpose of examination, is taken in the absolute sense.
Thus, in order to prevent bone density loss, the bone density loss would entirely stop in all cases at all times. The skilled artisan would view the prevention of bone density loss as highly unlikely since all cases would not be preventable by the administration of stem cells. Thus, it would be highly unpredictable to prevent all cases of bone density loss by the administration of the claimed stem cells.
Applicants have provided no long-term results showing that all cases of bone density loss can be prevented by the administration of [the claimed stem cells, as would be required to support the “prevention” claim. 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. Thus, one of ordinary skill in the art would not have a reasonable expectation of successfully preventing a bone density loss by performing the claimed method. A method for preventing bone density loss is not enabled by the instant specification. Accordingly, claims 1-20 are properly rejected.
Claim 17 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant's specification is not found to be enabling for use of quantum dots for delivery of any and all NF-kappa B inhibitors. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to carry out the method of the invention commensurate in scope with the current claims.
Analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue or unreasonable experimentation. See Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916). The key word is 'undue,' not experimentation.' " (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Applicants' claims are directed to delivery of any NF-kappa B inhibitor using bone targeting quantum dots. The breadth of the claims includes any NF-kappa B inhibitor in any quantum dot regardless of the shell, coating or core.
The specification provides no examples of how to generate or use a quantum dot. At the time the invention was made it was known that quantum dots have to be carefully formulated with considerations of size, compatibility and surface functionalization. (See Zhao, p2-3). Therefore, there was a recognized level of unpredictability with regards to generation and delivery of quantum dots.
Due to the lack of teachings in the art regarding specific formulation and structure of delivery of any and all NF-kappa B inhibitors using quantum dots, and the recognized unpredictability in the area of drug delivery using quantum dots, a large amount of guidance and teachings would be necessary in order to be enabling for methods of such.
There is no guidance and teachings provided by Applicants in the instant specification regarding drug delivery using quantum dots. The Examiner acknowledges that the Office does not require the presence of working examples to be present in the disclosure of the invention (see MPEP §2164.02). However, in light of the state of the art, discussed above, which recognizes a high level of unpredictability in the field of drug delivery using quantum dots, the Office would require appropriate disclosure to support a method of delivery of NF-kappa B inhibitors using quantum dots. The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Thus, due to the high level of unpredictability in the art, the current specification would have to provide greater amounts of teachings and guidance directed to methods of carrying out the claimed invention.
Therefore, due to the sum of all the aforementioned factors, one of ordinary skill in the art, at the time the invention was made, would not expect success carrying out the claimed method of bone targeting using quantum dots to administer NF-kappa B inhibitor. Given that the art fails to recognize and Applicant has failed to demonstrate the claimed method, the skilled artisan would be faced with the impermissible burden of undue experimentation in order to practice the claimed invention. Accordingly, claim 17 is deemed properly rejected.
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.
Claims 1-4 and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) as evidenced by Karchmer (37th AIA A Aerospace Sciences Meeting and Exhibit; Jan 11, 1999; See PTO-892; hereinafter “Karchmer”) and Wuest et al (PLoS One. 2017 Jan 30; hereinafter “Wuest;” See PTO-892).
Regarding claim 1-4 and 9-11: Cazzaniga disclosed use of mesenchymal stem cells in simulated microgravity conditions in a Random Positioning Machine. (See Cazzaniga Abstract). Cazzaniga disclosed that “mesenchymal stem cells (as required by claims 9-10) respond to gravitational unloading by upregulating HSP60, HSP70, cyclooxygenase 2 and superoxide dismutase 2. Such an adaptive response might be involved in inducing the overexpression of some osteogenic transcripts, even though the threshold to induce the formation of bone crystal is not achieved.” (See Cazzaniga Abstract). It is known that RPM provides gravitational forces at 0.1-0.9
×
g
(See Wuest et al, PTO-892, p. 80, col. 2, last para). It is known that “The gravitational attraction of the earth at a typical orbital altitude of 325 km ( approx. 200 miles) is about 90% of the gravitational attraction at the surface of the earth.” (Karchmer, p. 2, col. 1, 2nd para), as required by claim 3. Cazzaniga further disclosed that space-associated osteopenia is “linked to the impaired activity of osteoblasts and the increased function of osteoclasts as the result of gravitational unloading due to microgravity.” (Cazzaniga, p. 181, col. 1-2) as required by claim 4. It is also known that MSCs express beta1 integrins (See evidence in Togaratti Abstract) as required by claim 11.
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 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) in view of Kurpinski et al (Int J Radiat Oncol Biol Phys. 2009 Mar 1; herinafter "Kurpinski;" See PTO-892).
Regarding claims 18-20: The teachings of Cazzainga are set forth above. Cazzaniga taught that “simulated microgravity does not inhibit bMSC osteogenic differentiation in the presence of an osteogenic cocktail.” (See Cazzaniga p. 185, col. 1, para 2). Cazzaniga did not explicitly teach that MSC protect bone loss due to cosmic rays, solar flares and ions (such as those found in Van Allen radiation belt). Kurpinski compared the biological effects of X-rays and of high–linear energy transfer (LET) 56Fe ions on human mesenchymal stem cells (hMSC). Kurpinski taught that “During deep space missions, space crews encounter an elevated radiation environment that includes high-energy–charged (HZE) particles, such as 56Fe ions from the galactic cosmic rays” (See Kurpinski p. 870, col. 1, para 1). Kurpinski taught that “IR, even 1 Gy 56Fe ion irradiation, did not alter the in vitro osteogenic differentiation process of hMSC. Runx2, the master osteogenic transcription factor, is regulated by pErk1/2. Lack of changes in osteogenic differentiation was consistent with our observation that Runx2 expression and Erk1/2 activation did not change in hMSC after exposure to either X-rays or 56Fe ions.” (See Kurpinski p. 876, col. 1, 2nd para).
As such, one of ordinary skill in the art would be motivated to use the MSCs of Cazzaniga in environments such as exposure to particles trapped in the Earth's magnetic field, cosmic rays and solar flares. It is noted that both Cazzaniga and Kurpinski are directed to use of MSC in outer earth environments. It is noted that the combination of prior art would predictably yield a treatment for bone loss caused by microgravity and exposure to particles trapped in the Earth's magnetic field, cosmic rays and solar flares.
Claims 5 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) in view of Zwart et al (J Bone Miner Res. 2010 May; hereinafter "Zwart;" See PTO-892).
Regarding claim 5 and 16: The teachings of Cazzaniga are set forth above. Cazzaniga did not teach administration of NF-kappa B inhibitor prior to, subsequently with, or after administration of regenerative cells. Zwart “investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-kappaB ligand (RANKL) and on activation of NF-kappaB by tumor necrosis factor alpha (TNF-alpha) or exposure to modeled weightlessness.” (See Zwart Abstract). Zwart found that “NF-kappaB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids, inhibitor of NF-kappa B) was associated with reduced loss of bone mineral density after flight (p < .05).” (See Zwart Abstract). As such a person of ordinary skill in the art would have recognized the advantages of combining the complementary approaches to reduce bone density loss caused by microgravity. The person would have recognized that combination of MSC administration and NF-kappa B inhibitor would yield predictable result of reduction in bone density loss. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
It is also pointed out that Zwart taught that “[i]n cell culture models, simulated weightlessness increases TNF-α production,” (See Zwart p. 1054, col. 2, para 2), leading to NF-kappa B activation which is associated with loss of bone mineral density. (See Zwart Abstract), as required by claim 5.
Claims 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) in view ofKiatura et al (Int J Mol Sci. 2020 Jul 21; hereinafter "Kiatura;" See PTO-892).
Regarding claims 6-8: The teachings of Cazzniga are set forth above. Cazzaniga taught that space-associated osteopenia is “linked to the impaired activity of osteoblasts and the increased function of osteoclasts as the result of gravitational unloading due to microgravity.” (Cazzaniga, p. 181, col. 1-2). Cazzaniga did not teach that the increase osteoclast activity is associated with enhanced RANK ligand activity, enhanced interleukin-8 activity or enhanced interleukin-11 activity. However, Kitaura taught that RANKL, IL-8 and IL-11 are osteoclastogenesis-promoting cytokines (See Kitaura, p. 3, 1st para). As such a person of ordinary skill in the art would have recognized the advantages of combining the complementary approaches to reduce bone density loss caused by microgravity and increased osteoclast activity due to increased expression of RANKL, IL-8 and IL-11. The person would have recognized that combination of MSC administration in the bone density loss due to increased osteoclast activity due to increased expression of RANKL, IL-8 and IL-11 would yield predictable result of reduction in bone density loss.
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) in view of Aguirre-Vázquez A et al (Molecules. 2021 Mar 29; hereinafter "Aguirre-Vázquez A;" PTO-892).
Regarding claims 12-14: The teachings of Cazzniga are set forth above. Cazzniga did not teach use of epigenetic molecules for generation of reprogrammed cells as required by the instant claims. Aguirre-Vázquez taught use of “epigenetic molecules 5-aza-2′-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain.” (See Aguirre-Vázquez Abstract). As such it was known that stem cells can be regenerated using DNMT and HDAC inhibitors such as 5-aza and/or valproic acid. As such a person of ordinary skill in the art would have recognized the advantages of combining the teachings of Cazzaniga and Aguirre-Vázquez to use stem cells generated by administration of DNMT and HDAC inhibitors to reduce bone density loss caused by microgravity. The person would have recognized that stem cells can be generated by dedifferentiation can have therapeutic properties for treatment of bone loss.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) in view of Xin et al (Osteoporos Int. 2015 Nov; hereinafter "Xin;" PTO-892).
Regarding claim 15: The teachings of Cazzaniga are set forth above. Cazzaniga did not teach use antioxidants in combination with stem cells for treatment of bone density loss due to microgravity. Xin taught that “Curcumin might be an effective countermeasure for microgravity-induced bone loss but remains to be tested in humans.” (See Xin Abstract). As such a person of ordinary skill in the art would have recognized the advantages of combining the complementary approaches to reduce bone density loss caused by microgravity. The person would have recognized that combination of MSC administration and antioxidants like curcumin would yield predictable result of reduction in bone density loss.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Cazzaniga et al (Biochem Biophys Res Commun. 2016 Apr 22; herinafter "Cazzaniga;" See PTO-892) in view of Lee et al (RSC Adv. 2019 Jan 21; hereinafter "Lee;" PTO-892).
Regarding claim 17: The teachings of Cazzaniga are set forth above. Cazzaniga did not teach use quantum dots for bone targeting. Lee taught “[n]ovel fluorescent carbon dots (CDs) for bone imaging were fabricated via a facile hydrothermal method using alendronate in the absence of a nitrogen-doping precursor to enhance bone affinity.” (See Lee Abstract). Lee demonstrated that “CDs prepared from alendronate (Alen-CDs) bind to live zebrafish skull tissues with high affinity and selectivity, including a strong binding activity for calcium-deficient hydroxyapatite (CDHA) scaffolds, and rat femur.” (ref). Lee indicated that their discovery supporting the use of fluorescent CDs in the treatment of various bone diseases such as osteoporosis, Paget's disease, and metastatic bone cancer. (See Lee Abstract). As such one of ordinary skill in the art would have been motivated to combine small molecule delivery, such as a NF-kappa B inhibitor using a carbon dot as elucidated in Lee.
Conclusion
No claim is free of art.
No claim is allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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 M. 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.
/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633