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 04/27/2026 are acknowledged. Claims 1 is amended. Claims 1, 5-6, 8, 11, 17-18, 41 and 59 are examined on the merits within and are currently pending.
Maintained 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 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). 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).
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. 5. 6. 8. 11. 17 and 18
Applicant argues that Applicant acknowledges the withdrawal of the previous 103 rejection based on Friedlander, Green, Hoh and Hosaka, Hoh and Scott, Patel, Zhu and Le.
However, the Examiner now rejects claims 1, 5, 6, 8, 11, 17 and 18 based on a reduced
subset of these same cited references, and states that the rejection is modified.
Applicant's arguments have been fully considered and they are not persuasive since the modified rejection based on a different set of prior arts: Green, Hoh and Scott, Friedlander, Hoh and Osaka, Le, Brenner, Zhu, Patel and Hosaka.
Applicant argues that nowhere do any of the previous cited references, or the newly presented combination of already cited references, describe the presentation of a first therapeutic agent, comprising MCP-1 and/or osteopontin and a second therapeutic agent comprising an inhibitor of at least one of IL-17A, CXCL 1, or IL-6. Friedlander may teach repairing retinal vascular injury for treating or preventing ocular vascular disorders but one skilled in the art would not be led to apply this teaching to an aneurysm coil. Retinal vascular disorders are not treated with aneurysm coils, and indeed, doing so would be catastrophic and lead to blindness. There is simply no motivation to apply the teachings of Friedlander to other references related to aneurysms treated with a coil. It is well known in the art that aneurysm coils are used to treat aneurysms in the brain.
Applicant's arguments have been fully considered and they are not persuasive since Friedlander teaches MCP-1 (CCL2), Green teaches IL-6, Hoh and Hosaka and Zhu teach IL-17A and Patel teaches CXCL1. Friedlander teaches retina vascular diseases, but 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. 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. Previous claims do not have limitations of retina and current claims have limitations of brain aneurysm.
Applicant argues that Green teaches the administration of a hemichannel blocker for purposes of reducing certain cytokines for treatment of many different conditions, such as diabetic retinopathy, cancer, muscular dystrophy, and inflammatory diseases, but it is silent with respect to the treatment of brain aneurysms. Green provides no teaching for use of any compounds for treating aneurysms and is not relevant to an aneurysm coil. Reference to a vessel leak in Green relates to capillary leakage which is a leakage of small vessels in the retina often due to diabetic retinopathy, and is not related to aneurysms. Therefore, one skilled in the art would not be motivated to somehow combine the teachings of Green with another reference related to treating aneurysms. Hoh and Hosaka does discuss IL-17A inhibition, but as the Examiner acknowledges, is silent regarding an aneurysm coil. Hoh and Scott teach aneurysm coils coated with PLGA coating that releases MCP-1, but is silent regarding a second therapeutic agent, much less a coating that would sequentially release a second therapeutic agent. Patel et al. teach implanting an aneurysm coil coated with CXCL 1. Patel is silent on the sequential release of two different agents for treating an aneurysm, and consequently cannot suggest a unique coating for an aneurysm coil that provides sequential release. Zhu’s reference is limited to ocular neovascularization and is silent regarding the healing mechanisms involved with healing a large lesion such as a brain aneurysm. Le’s reference looks at cutaneous wound healing and is completely silent with respect to aneurysms such as brain aneurysms.
Applicant's arguments have been fully considered and they are not persuasive since the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things. A lesion can occur anywhere in or on the body, such as the skin, blood vessels, brain, and other organs. 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. (Common knowledge). Green et al. teach cytokine modulation. The cytokines to be modulated include IL-6, MCP-1. Hoh and Hosaka et al. teach IL-17A inhibition was shown to prevent aneurysm formation and rupture. Hoh and Scott et al. and Patel et al. teach positioning an aneurysm coil at the aneurysm. 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 41,
Applicant argues that for all of the reasons provided above, a combination of cited references simply does not teach or suggest an aneurysm device comprising a polymer incorporating a first therapeutic agent and a second therapeutic agent therein, claim 41 is not obvious.
Applicant's arguments have been fully considered and they are not persuasive since all explanations above. The rejection of claim 41 is maintained.
Claim 59,
Applicant argues that for Claim 59 the cited references do not teach all of the elements recited in claim 59. Sanes is related to treating neuronal lesions not aneurysms. Hosaka is related to treatment of aneurysms but not neurons. One skilled in the art would not be led to combine an agent related to neuronal tissue repair with another agent that is involved with vascular repair, or vice versa. Specifically, 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 since again the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things. Claim 59 is rejected by Hoh and Schott, Sanes and Hosaka. Especially, 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. 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). "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. Sanes teaches osteopontin (OPN) as a treatment for neuronal lesions. Administering of the pro-regenerative OPN fragment to a subject occurs within a recent time frame of the injury, which includes, without limitation, contacting within 12-48 hours following the injury or within 1-7 days of the injury. Administering at a later point following the injury may also have some benefit. Claim 59 is taught and the rejection is maintained.
Conclusion
Applicants' 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 extension fee 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 date of this final action.
Correspondence
No claim is allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGOC-ANH THI NGUYEN whose telephone number is (571)270-0867. The examiner can normally be reached Monday - Friday 8:00 am.
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, Robert A Wax can be reached on 571-272-0623. 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.
/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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