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 .
Status of Application
Applicants' arguments/remarks filed 10/28/2025 are acknowledged. Claims 1, 5-6, 8, 11, 41 and 59 are amended. Claims 4, 7, 9-10 and 12-15 are newly canceled. Claims 1, 5-6, 8, 11, 17-18, 41 and 59 are examined on the merits within and are currently pending.
Withdrawn Rejections
With applicants' amendment filed 05/19/2025 and with respect to the objection:
The rejection of Claim(s) 4, 7, 9-10 and 12-15 under 35 U.S.C. 103 has been withdrawn due to the cancelation of these claims.
The rejection of Claim(s) 1, 4-15 and 17-18 under 35 U.S.C. 103 over Green et al., Hoh and Scott, et al., (Monocyte Chemotactic Protein-1…), Friedlander et al., Hoh and Osaka et al., (Estrogen Deficiency…), Le et al., and Brenner et al., Zhu et al., Patel et al. and Hosaka et al. has been withdrawn due to the amendment of claim 1.
The rejection of Claim 41 under 35 U.S.C. 103 over Green et al., Hoh and Scott, et al., (Monocyte Chemotactic Protein-1…), Friedlander et al., Hoh and Osaka et al., (Estrogen Deficiency…), Le et al., and Brenner et al., Zhu et al., Patel et al. and Friedlander et al. has been withdrawn due to the amendment of claim 41.
Modified 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 non-obviousness.
A lesion is an area of abnormal or damaged tissue caused by injury, infection, or disease. A lesion can occur anywhere in or on the body, such as the skin, blood vessels, brain, and other organs. Examples of lesions include wounds, ulcers, abscesses, sores, cysts, and tumors. A lesion may be benign (not cancer) or malignant (cancer). (Common knowledge). ((https://www.cancer.gov/publications/dictionaries/cancer-terms/def/lesion).
"Aneurysm coil at the lesion site" means that the small metal coils used to treat an aneurysm have been successfully placed directly within the weakened area of the blood vessel (the "lesion") where the aneurysm is located, effectively blocking blood flow to that spot and preventing it from rupturing; this is the intended outcome of an endovascular coiling procedure.
Claims 1, 5-6, 8, 11 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Friedlander et al. (WO 2011065968 A1), Green et al. (US 2019/0030122 Al) and Hoh and Osaka et al. (Hoh and Osaka et al., Estrogen Deficiency Promotes Cerebral Aneurysm Rupture by Upregulation of Th17 Cells and Interleukin-17A Which Downregulates E-Cadherin. J Am Heart Assoc. 2018;7:e008863), in view of Hoh and Scott et al. (Hoh and Scott, et al., Monocyte Chemotactic Protein-1 Promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms via a Macrophage Inflammatory Protein-1α and Macrophage Inflammatory Protein-2-Dependent Pathway. Circulation. 2011 November 15; 124(20): 2243–2252) and Patel et al. (Patel et al., Inflammation in murine aneurysm healing: The role of CXCL1. JNIS 2019;11(Suppl 1):A1–A134) and further in view of Zhu et al. (Zhu et al., Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization. 2015 John Wiley & Sons Ltd, Immunology, 147, 414-428) and Le et al. (US 20130295058 A),
Claims 1,
Friedlander et al. teach methods and related compositions for repairing retinal vascular injury and for treating or preventing ocular vascular disorders. The methods entail administering to a subject in need of treatment a pharmaceutical composition that contains an effective amount of a monocyte chemoattractant compound. The pharmaceutical composition is preferably administered by intravitreal injection (Abs), MCP-1 (CCL2), which recruit monocytes and macrophages to treat or ameliorate symptoms of ocular vascular diseases or degenerative disorders. (0021). MCP-1 is the 1st therapeutic agent. (Googled: M2 macrophages are a subtype of macrophages, characterized by their anti-inflammatory and tissue repair functions. They are distinct from the classically activated M1 macrophages, which are pro-inflammatory. While M2 macrophages are primarily associated with promoting wound healing, both M1 and M2 macrophages play crucial roles in the process, but at different stages. M1 macrophages initiate the inflammatory response, clearing debris and pathogens, while M2 macrophages are crucial for tissue repair and resolution of inflammation).
Friedlander et al. teach a monocyte chemoattractant compound MCP-1/CCL2 (0021) or CX3CL1 (0009), but do not teach CXCL1.
Green et al. teach cytokine modulation (title) and the use of hemichannel blockers to
modulate cytokine levels in a subject to the use ofhemichannel blockers to reduce or level cytokine activity, including in conditions characterized in whole or in part by angiogenesis and/or vessel leak. (Abs). The cytokines to be modulated include IL-6, MCP-1. (0002) and more specifically, IL-6 receptor blockers, as well as other regulators, and regulators of other cytokines and/or their receptors, including MCP-1. (0014). IL-6 is the second therapeutic agent.
Hoh and Hosaka et al. teach IL-17A inhibition was shown to prevent aneurysm formation and rupture. Secondly, estrogen deficiency upregulates T helper 17 cells and IL-17A and promotes aneurysm rupture. Estrogen-deficient mice had more ruptures than control mice. Estradiol supplementation or IL-17A inhibition decreased the number of ruptures in estrogen-deficient mice. Thirdly, IL-17A-blockade protects against aneurysm formation and rupture by increased E-cadherin expression. (Abs).
Friedlander et al., Green et al. Hoh and Hosaka et al.do not teach positioning an aneurysm coil at the aneurysm, nor the coil comprising a polymer coating a first therapeutic agent and a second therapeutic agent, and the polymer is capable of controlled release of the first therapeutic agent and/or the second therapeutic agent.
Hoh and Scott et al. teach coils with a PLGA coating that released MCP-1 and performed a dose-response study for effect on intra-aneurysmal tissue healing in a murine carotid aneurysm model. MCP-1-releasing coils promote significantly greater aneurysm tissue ingrowth. MCP-1-recruited fibroblasts and macrophages are derived from the bone marrow. MCP-1-mediated vascular inflammatory repair. (Abs, Methods and Results). The three different doses of MCP-1-releasing coils were micro-surgically implanted into fully developed murine carotid aneurysms. (pg. 3, 2nd par.). MCP-1 promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms (Title) is administered in coated coils which slowly release MCP-1 over 21 days and implanted them in our murine carotid aneurysm model. PLGA coating to slowly release protein available in various compositions so that the rate of release can be varied as needed. (pg. 5, 1st par.).
Patel et al. teach using murine aneurysm healing model, were implanted with either poly(lactic-co-glycolic acid)(PLGA)+CXCL1 – coated coils or PLGA only - coated coils. (A55, left col., Methods). CXCL1 decreases murine aneurysm healing after coil implantation. Therapeutic intervention with CXCL1 neutralizing antibody appears to increase aneurysm healing after coil implantation. (pg. A55, Conclusion).
Hoh and Scott et al. and Patel et al. teach positioning an aneurysm coil at the aneurysm, and Hoh and Scott et al. teach the coil comprising a polymer coating a first therapeutic agent and Patel et al. teach a second therapeutic agent, and the polymer is capable of controlled release of the first therapeutic agent. Friedlander et al. teach MCP-1 (CCL2), which recruit monocytes and macrophages to treat or ameliorate symptoms of ocular vascular diseases or degenerative disorders.
Friedlander et al., Green et al. Hoh and Scott et al. and Patel et al. do not teach an inhibitor of IL-17A, CXCL 1, or IL-6 effective to promote polarization of an amount of the macrophages to M2 macrophages at the lesion site.
Zhu et al. teach Interleukin-17A neutralization alleviated ocular neovascularization
by promoting M2 and mitigating M1 macrophage polarization. (Abs). M2 macrophages
secreted endothelial cell growth and angiogenic factors such as VEGF and CXCL1 and were considered to promote wound repair and NV. (pg. 425, right col., 3rd par.).
Le et al. teach cutaneous wound healing represents a highly coordinated process to achieve tissue homeostasis, which involves complex interactions of different types of resident cells and infiltrating immune cells as well as their secreted soluble mediators. The repair process involves three distinct but overlapping phases: inflammation, tissue formation, and remodeling. Upon tissue insult, the immediate inflammatory response is characterized by infiltration and activation of leukocytes, whereas a delayed or excessive inflammatory response may lead to abnormal wound healing in diabetic patients, scarring and fibrotic diseases. Aside from leukocytes which act as the principal cellular component of the early inflammatory response, macrophages contribute to all stages of wound repair. Particularly, several studies have shown that M2 macrophages can produce mediators essential in the resolution of inflammation and tissue modeling, thus promoting wound repair. (0004). Specific blocking of IL-6 and GM-CSF inhibited the induction of M2-like macrophages (FIG. 5A, 5B), indicating that both IL-6 and GM-CSF could contribute to GMSC-induced polarization of M2 macrophages. (0054).
Friedlander et al. teach that the observed repair effect is mediated by macrophages that are recruited into the retina in response to these chemotactic factors. (0067). Chemotactic factors such as MCP-1 are first therapeutics during inflammation phase.
Friedlander et al. and Le et al. teach MCP-1 should be released first, so MCP-1 should be in the outside coating layer, while CXCL1 is inside of coating layer.
It would have been obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to treat a lesion by administering to a subject in need of treatment a pharmaceutical composition that contains an effective amount of a monocyte chemoattractant compound, MCP-1 (CCL2), which recruit monocytes and macrophages to treat or ameliorate symptoms of ocular vascular diseases or degenerative disorders, taught by Friedlander et al., by modulating MCP-1 and IL-6 blocker levels, taught by Green et al., IL-17A inhibitor prevent aneurysm, taught by Hoh and Hosaka, by administering MCP-1 promoting macrophage at the lesion area, by a device, a polymer for controlled release, taught by Hoh and Scott et al., while by administering a compound to inhibit the expression or activity of CXCL1 helping wound healing and reducing aneurysm rupture, taught by Patel et al., since "Aneurysm coil at the lesion site" means that the small metal coils used to treat an aneurysm have been successfully placed directly within the weakened area of the blood vessel (the "lesion") where the aneurysm is located, effectively blocking blood flow to that spot and preventing it from rupturing; this is the intended outcome of an endovascular coiling procedure. Hoh and Scott et al. and Patel et al. have proven aneurysm coil to coat with MCP-1 and CXCL1 work, so one of ordinary skill in the art could combine MCP-1 and CXCL1 in coil. And Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization. to promote wound repair and NV, taught by Zhu et al. and Le et al., and Friedlander et al. and Le et al. teach MCP-1 should be released first, so MCP-1 should be in the outside coating layer, while CXCL1 is inside of coating layer, as they have proven they are steps should be included for aneurysm treatments.
With regard to claim 5, Hoh and Scott et al. teach three different doses of MCP-1-releasing coils (100 μg/mL, 1 mg/mL, and 10 mg/ mL) were microsurgically implanted into 3-week fully developed murine carotid aneurysms. Coil implantation was performed by microsurgically inserting coils via a distal portion of the aneurysm and advancing into a proximal saccular part of the aneurysm. Implanted aneurysms were harvested three weeks later to analyze. (pg. 3, 2nd par.).
With regard to claims 6, 8 and 11,
Patel et al. teach aneurysms were implanted with either poly(lactic-co-glycolic acid)(PLGA)+CXCL1 – coated coils or PLGA only - coated coils. Three weeks after coil implantation, aneurysms were harvested for histological quantification of aneurysm healing. (pg. A55, left col., Methods, 2nd par.). animals treated with PLGA+CXCL1 - coated coils had significantly less aneurysm healing than those treated with PLGA only - coated coils (21.8% ± 3.87 versus 39.8% ± 8.02, respectively; p = 0.048). In the second experiment, animals treated with CXCL1 neutralizing antibody had significantly increased aneurysm healing compared to those treated with IgG control (63.8% ± 3.69 versus 42.4% ± 3.55, respectively; p = 0.00012).
Conclusion: Our findings suggest CXCL1 decreases murine aneurysm healing after coil implantation. Therapeutic intervention with CXCL1 neutralizing antibody appears to increase aneurysm healing after coil implantation. (pg. A55, left col., Results and Conclusion, 3rd and 4th pars.).
With regard to claim 17,
Patel et al. teach using murine aneurysm healing model, were implanted with either poly(lactic-co-glycolic acid)(PLGA)+CXCL1 – coated coils or PLGA only - coated coils. (A55, left col., Methods). CXCL1 decreases murine aneurysm healing after coil implantation. Therapeutic intervention with CXCL1 neutralizing antibody appears to increase aneurysm healing after coil implantation. (pg. A55, Conclusion).
Hoh and Hosaka et al. teach IL-17A inhibition was shown to prevent aneurysm formation and rupture. Secondly, estrogen deficiency upregulates T helper 17 cells and IL-17A and promotes aneurysm rupture. Estrogen-deficient mice had more ruptures than control mice. Estradiol supplementation or IL-17A inhibition decreased the number of ruptures in estrogen-deficient mice. Thirdly, we found that IL-17A-blockade protects against aneurysm formation and rupture by increased E-cadherin expression. IL-17-inhibited mice had increased E-cadherin expression. (Abs).
With regard to claim 18,
Patel et al. teach using murine aneurysm healing model, were implanted with either poly(lactic-co-glycolic acid)(PLGA)+CXCL1 – coated coils or PLGA only - coated coils. (A55, left col., Methods). CXCL1 decreases murine aneurysm healing after coil implantation. Therapeutic intervention with CXCL1 neutralizing antibody appears to increase aneurysm healing after coil implantation. (pg. A55, Conclusion).
Hoh and Hosaka et al. teach IL-17A inhibition was shown to prevent aneurysm formation and rupture. Secondly, estrogen deficiency upregulates T helper 17 cells and IL-17A and promotes aneurysm rupture. Estrogen-deficient mice had more ruptures than control mice. Estradiol supplementation or IL-17A inhibition decreased the number of ruptures in estrogen-deficient mice. Thirdly, we found that IL-17A-blockade protects against aneurysm formation and rupture by increased E-cadherin expression. IL-17-inhibited mice had increased E-cadherin expression. (Abs).
Le et al. teach several studies have shown that M2 macrophages can produce mediators essential in the resolution of inflammation and tissue modeling, thus promoting wound repair. (0004). Specific blocking of IL-6 and GM-CSF inhibited the induction of M2-like macrophages (FIG. 5A, 5B), indicating that both IL-6 and GM-CSF could contribute to GMSC-induced polarization of M2 macrophages. (0054).
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Friedlander et al. (WO 2011065968 A1), Green et al. (US 2019/0030122 Al), Hoh and Scott et al. (Hoh and Scott, et al., Monocyte Chemotactic Protein-1 Promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms via a Macrophage Inflammatory Protein-1α and Macrophage Inflammatory Protein-2-Dependent Pathway. Circulation. 2011 November 15; 124(20): 2243–2252), Hoh and Osaka et al. (Hoh and Osaka et al., Estrogen Deficiency Promotes Cerebral Aneurysm Rupture by Upregulation of Th17 Cells and Interleukin-17A Which Downregulates E-Cadherin. J Am Heart Assoc. 2018;7:e008863), Zhu et al. (Zhu et al., Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization. 2015 John Wiley & Sons Ltd, Immunology, 147, 414-428), Le et al. (US 20130295058 A), Patel et al. (Patel et al., Inflammation in murine aneurysm healing: The role of CXCL1. JNIS 2019;11(Suppl 1):A1–A134) and further in view of Friedlander et al. (WO 2011065968 A1).
Friedlander et al. teach methods and related compositions for repairing retinal vascular injury and for treating or preventing ocular vascular disorders. The methods entail administering to a subject in need of treatment a pharmaceutical composition that contains an effective amount of a monocyte chemoattractant compound. The pharmaceutical composition is preferably administered by intravitreal injection (Abs), MCP-1 (CCL2), which recruit monocytes and macrophages to treat or ameliorate symptoms of ocular vascular diseases or degenerative disorders. (0021). MCP-1 is the 1st therapeutic agent. (Googled: M2 macrophages are a subtype of macrophages, characterized by their anti-inflammatory and tissue repair functions. They are distinct from the classically activated M1 macrophages, which are pro-inflammatory. While M2 macrophages are primarily associated with promoting wound healing, both M1 and M2 macrophages play crucial roles in the process, but at different stages. M1 macrophages initiate the inflammatory response, clearing debris and pathogens, while M2 macrophages are crucial for tissue repair and resolution of inflammation).
Friedlander et al. teach a monocyte chemoattractant compound MCP-1/CCL2 (0021) or CX3CL1 (0009), but do not teach CXCL1.
Green et al. teach cytokine modulation (title) and the use of hemichannel blockers to
modulate cytokine levels in a subject, including the angiogenic cytokine, VEGF, and their production, secretion and/or release, and to the use of hemichannel blockers to reduce
or level cytokine activity, including in conditions characterized in whole or in part by angiogenesis and/or vessel leak. (Abs). The cytokines to be modulated include IL-6, MCP-1. (0002) and more specifically, IL-6 receptor blockers, as well as other regulators, and regulators of other cytokines and/or their receptors, including MCP-1. (0014).
Hoh and Scott et al. teach MCP-1 promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms (Title) is administered in coated coils which slowly release MCP-1 over 21 days and implanted them in our murine carotid aneurysm model. PLGA coating to slowly release protein available in various compositions so that the rate of release can be varied as needed.
(pg. 5, 1st par.).
Friedlander et al. teach that the observed repair effect is mediated by macrophages that are recruited into the retina in response to these chemotactic factors. (0067). Chemotactic factors such as MCP-1 are first therapeutics during inflammation phase.
Hoh and Hosaka et al. teach IL-17A inhibition was shown to prevent aneurysm formation and rupture. Secondly, estrogen deficiency upregulates T helper 17 cells and IL-17A and promotes aneurysm rupture. Estrogen-deficient mice had more ruptures than control mice. Estradiol supplementation or IL-17A inhibition decreased the number of ruptures in estrogen-deficient mice. Thirdly, IL-17A-blockade protects against aneurysm formation and rupture by increased E-cadherin expression. (Abs).
Patel et al. teach using murine aneurysm healing model, were implanted with either poly(lactic-co-glycolic acid)(PLGA)+CXCL1 – coated coils or PLGA only - coated coils. (A55, left col., Methods). CXCL1 decreases murine aneurysm healing after coil implantation. Therapeutic intervention with CXCL1 neutralizing antibody appears to increase aneurysm healing after coil implantation. (pg. A55, Conclusion).
Zhu et al. teach Interleukin-17A neutralization alleviated ocular neovascularization
by promoting M2 and mitigating M1 macrophage polarization. (Abs). M2 macrophages
secreted endothelial cell growth and angiogenic factors such as VEGF and CXCL1 and were considered to promote wound repair and NV. (pg. 425, right col., 3rd par.).
Le et al. teach cutaneous wound healing represents a highly coordinated process to achieve tissue homeostasis, which involves complex interactions of different types of resident cells and infiltrating immune cells as well as their secreted soluble mediators. The repair process involves three distinct but overlapping phases: inflammation, tissue formation, and remodeling. Upon tissue insult, the immediate inflammatory response is characterized by infiltration and activation of leukocytes, whereas a delayed or excessive inflammatory response may lead to abnormal wound healing in diabetic patients, scarring and fibrotic diseases. Aside from leukocytes which act as the principal cellular component of the early inflammatory response, macrophages contribute to all stages of wound repair [23-25]. Particularly, several studies have shown that M2 macrophages can produce mediators essential in the resolution of inflammation and tissue modeling, thus promoting wound repair. (0004). Specific blocking of IL-6 and GM-CSF inhibited the induction of M2-like macrophages (FIG. 5A, 5B), indicating that both IL-6 and GM-CSF could contribute to GMSC-induced polarization of M2 macrophages. (0054).
Second therapeutics such as IL-17A, CXCL1 or IL-6 promote wound repair with M2 macrophages.
It would have been obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to treat a lesion, which include tetinal vascular injury, taught by Friedlander et al., by modulating MCP-1 and IL-6 blocker levels, taught by Green et al, by administering MCP-1 promoting macrophage at the lesion area, by a device, a polymer for controlled release, taught by Hoh and Scott et al., while by administering a compound to inhibit the expression or activity of CXCL1 helping wound healing and reducing aneurysm rupture, taught by Patel et al. since "Aneurysm coil at the lesion site" means that the small metal coils used to treat an aneurysm have been successfully placed directly within the weakened area of the blood vessel (the "lesion") where the aneurysm is located, effectively blocking blood flow to that spot and preventing it from rupturing; this is the intended outcome of an endovascular coiling procedure. Hoh and Scott et al. and Patel et al. have proven aneurysm coil to coat with MCP-1 and CXCL1 work, so one of ordinary skill in the art could combine MCP-1 and CXCL1 in coil. And Friedlander et al. and Le et al. teach MCP-1 should be released first, so MCP-1 should be in the outside coating layer, while CXCL1 is inside of coating layer.
Claim 59 is rejected under 35 U.S.C. 103 as being unpatentable over Hoh and Scott et al. (Hoh and Scott, et al., Monocyte Chemotactic Protein-1 Promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms via a Macrophage Inflammatory Protein-1α and Macrophage Inflammatory Protein-2-Dependent Pathway. Circulation. 2011 November 15; 124(20): 2243–2252) in view of Sanes et al. (WO 2019036331 A1), and Hosaka et al. (Hosaka et al., Monocyte Chemotactic Protein-1–Interleukin-6–Osteopontin Pathway of Intra-Aneurysmal Tissue Healing. Stroke, pg. 1052-1060, April 2017).
Hoh and Scott et al. teach MCP-1 promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms (Title) is administered in coated coils which slowly release MCP-1 over 21 days and implanted them in our murine carotid aneurysm model. PLGA coating to slowly release protein available in various compositions so that the rate of release can be varied as needed. It has been used in other implantable devices that have been cleared by the FDA for human use in several applications, and a significant background literature is available on expected behavior in
vivo. (pg. 5, 1st par.).
Hoh and Scott et al. do not teach polymer coating osteopontin in a second portion.
Sanes et al. teach osteopontin (OPN) as a treatment for neuronal lesions. (Title). The invention described herein relates to a method of treating neuronal lesion in the central nervous system. (0074). In one embodiment, administering of the pro-regenerative OPN fragment to a subject occurs within a recent time frame of the injury. Examples of such time frames, include, without limitation, contacting within 12 hours following the injury. Other such time frames are contacting the neuron within 24, 36, and 48 hours of the injury. Other such time frames are contacting the neuron within 1, 2, 3, 4, 5, 6, and 7 days of the injury. Administering at a later point following the injury may also have some benefit. (0075).
Hosaka et al. teach the local delivery of monocyte chemotactic protein-1 (MCP-1) via an MCP-1–releasing poly(lactic-co-glycolic acid)–coated coil promotes intra-aneurysmal tissue healing. Osteopontin is downstream mediators in the MCP-1–mediated aneurysm-healing pathway and osteopontin-releasing coil significantly promotes intra-aneurysmal healing.
It would have been obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to treat a lesion, which include wounds, ulcers, abscesses, sores, cysts, and tumors, by administering MCP-1 promoting macrophage at the lesion area, taught by Hoh and Scott et al., during up to 21 days, and by administering cytokine MCP-1 with osteopontin, taught by Sanes, for up to 7 days or longer, and osteopontin significantly promotes intra-aneurysmal healing and is downstream mediators in the MCP-1–mediated aneurysm-healing pathway, taught by Hosaka et al., since they have been proven so and it would be obvious that MCP-1 should be in the outermost layer and released first and osteopontin should be in a second portion and released after MCP-1. Hoh and Scott et al. and Patel et al. teach positioning an aneurysm coil at the aneurysm, and Hoh and Scott et al. teach the coil comprising a polymer coating a first therapeutic agent and Patel et al. teach a second therapeutic agent, and the polymer is capable of controlled release of the first therapeutic agent.
Response to Arguments
Regarding rejection under 35 USC 103
Claims 1, 4-15. 17 and 18 and 41
Applicant argues that the amendments obviate this rejection. Claim 1 has been amended to incorporate the positioning of an aneurysm coil comprising the elements of claim 41. Claim 41 is not rejected on these grounds. Therefore, logically, the amendments to claim 1 obviate this rejection with respect to claim 1 and dependent claims 5, 6, 8, 11, 17, and 18. Reconsideration and withdrawal of this rejection is requested.
and Claim 41: Applicant argues that The combination of references simply does not teach a device comprising a polymer incorporating a first therapeutic agent and a second therapeutic agent therein, wherein the polymer is capable of controlled release of the first therapeutic agent and the second therapeutic agent. In addition, the prior art does not teach such a polymer
that has MCP-1 and/or osteopontin in an outermost layer and an inner layer comprising
an inhibitor of at least one of IL-17 A, CXCL 1, or IL-6. With the cited art being silent with
respect to these and other elements, claim 41 is not obvious.
Applicant's arguments have been fully considered and they are persuasive according to previous office action, however, this office action modified rejections of these claims to respond to the amendments so that arguments have been fully considered and they are not persuasive. Please see the modified rejections above.
Applicant's arguments have been fully considered and they are persuasive according to previous office action, however, this office action modified rejections of these claims to respond to the amendments so that arguments have been fully considered and they are not persuasive according to modified rejection of this office action. Please see the modified rejections above. Similarly to the rejection of both claims 1 and 41, Friedlander et al. teach methods and related compositions for repairing retinal vascular injury and for treating or preventing ocular vascular disorders, which is a specific type of retinal vascular injury, often leading to hemorrhage and so, retinal aneurysm is a form of retinal vascular injury, causing aneurysm; the aneurysm itself is the underlying vascular problem. Also, similar to modified rejections of claim 1, Green et al. teach cytokine modulation of two types of therapeutics IL-6 and MCP-1; one with skill in the art would learn that these two groups of therapeutics help treating aneurysm. And Le et al. teach the repair process involves three distinct but overlapping phases: inflammation, tissue formation, and remodeling; Zhu et al. teach Interleukin-17A neutralization alleviated ocular neovascularization
by promoting M2 and mitigating M1 macrophage polarization to promote wound repair and NV, so one with skill in the art would learn to improve inflammation first with first group of therapeutics and then to promote tissue formation, and remodeling with second group of therapeutics, but they are overlapping phases, so one with skill in the art would learn to have the first group of therapeutics outside to release first and second group of therapeutics inside to release next, and somewhat overlapping.
Claim 59,
Applicant argues the cited references do not teach all of the elements recited in claim 59. None of the references discuss a composition that comprises both MCP-1 and osteopontin. Further still, none of the cited references teach a composition where the MCP-1 and osteopontin are combined with the pharmaceutically effective carrier such that MCP-1 is released for a first
predetermined duration of time and osteopontin is released for a second predetermined duration of time beginning after the start of the first predetermined duration of time, wherein, optionally, the first predetermined duration is 1-14 days and, optionally, the second predetermined duration is 1-14 days.
Applicant's arguments have been fully considered and they are not persuasive because each prior art teaches one kind of therapeutic: Hoh and Scott et al. teach MCP-1 promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms (Title) is administered in coated coils which slowly release MCP-1 over 21 days; Sanes et al. teach osteopontin (OPN) as a treatment for neuronal lesions and other such time frames are contacting the neuron within 1, 2, 3, 4, 5, 6, and 7 days of the injury, also administering at a later point following the injury may also have some benefit.; Hosaka et al. teach Osteopontin is downstream mediators in the MCP-1–mediated aneurysm-healing pathway and osteopontin-releasing coil significantly promotes intra-aneurysmal healing, so one with skill in the art would learn to improve inflammation first with first group of therapeutics and then to promote tissue formation, and remodeling with osteopontin as downstream mediator in aneurysm healing, but they are overlapping phases, so one with skill in the art would learn to have the first group of therapeutics outside to release first and second group of therapeutics inside to release next, and somewhat overlapping.
Conclusion
No claim is allowed.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615