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
Claims 1, 3, 21-23 and 27-28 are pending and presented for examination.
Election/Restrictions
Applicant elected
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without traverse in the reply filed on 4/3/2024. Claim 21 was amended to add several structurally and chemically different compounds that are distinct from elected compound C0105M except for
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, which is considered to be a an obvious variant of C0105M and is also considered and searched for examination on the merits.
Priority
This application claims priority from application Serial No. 63/109,213, filed on 11/3/2020.
Information Disclosure Statement
No Information Disclosure Statement filed was filed with Applicant’s recent reply.
Withdrawn Claim Objections/Rejections
Claim 3 was objected to due to an informality that was fixed by amendment. Therefore, the objection is hereby withdrawn.
Response to Arguments
Applicant’s arguments with respect to claim(s) 3/13/22026 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 103
New rejection, necessitated by amendment
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.
Maintained - Claims 1, 3, 21-23 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over
Barbier et al. (US PG-PUB 2011/0105481 – previously cited) in view of
Han et al. (Folia Neuropathol. 2020; 58 (1): 57-69 DOI: https://doi.org/10.5114/fn.2020.94007 - previously cited) and
Strela et al. (Life Sciences, Volume 241, 2020 Jan 15, 117098, ISSN 0024-3205, https://doi.org/10.1016/j.lfs.2019.117098. (https://www.sciencedirect.com/science/article/pii/S0024320519310252).
Claimed invention
The claims are drawn to inhibiting an immune response mediated by one or more of TLR2, RAGE, CCR5, CXR4 and CD4 cell surface receptors in a subject having a hyperinflammatory syndrome (e.g., hypotensive shock), the method comprising administering to the subject an effective amount of a compound such as
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in the absence of a mu opioid receptor (MOR)-binding effective amount of a separate MOR agonist or antagonist.
Prior art
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
Barbier does not expressly teach RAGE, TLR2 or treating hypotensive shock.
However, it was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
Double Patenting
New rejections, necessitated by amendment
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
A. New rejection - Claims 1, 3, 8, 9, 21-23, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 8,614,324 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims are drawn to compounds of formula II which include compounds such as
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which is a species of the instant formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference specification at col. 5:57 to col. 6:2. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
B. New rejection - Claims 1, 3, 8, 9, 21-23 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10,017,736 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference Abstract; see also col. 67:~22-25. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
C. New rejection - Claims 1, 3, 8, 9, 21-23, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,760,052 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference Abstract; see also col. 68:~49-52. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
D. New rejection - Claims 1, 3, 21-23, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,661,580 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference Abstract; see also col. 69:~49-57. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
E. New rejection - Claims 1, 3, 21-23, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,370,791 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference specification, col. 1:~14-38; see also col. 17:~59-65. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
F. New rejection - Claims 1, 3, 21-23 and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 12,065,440 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference, col. 1:~16-40; see also col. 17:~48-54. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
G. New rejection - Claims 1, 3, 21-23 and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,391,693 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference Title; Abstract; see also col. 17:~48-52. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
H. New rejection - Claims 1, 3, 21-23 and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 9,354,223 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference Abstract; see also paragraph bridging columns 64 and 65. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide-activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
I. New rejection - Claims 1, 3, 21-23 and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,500,640 B2 (reference) in view of Barbier et al., Han et al. and Strela et al. (each cited above).
The reference claims teach compounds of a formula that include compounds such as
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which is a species of the instant claimed formula. The utility of the compound is to bind to FLNA and thereby inhibit inflammation. See reference Abstract; see also col. 67:~18-31. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of each claim set have the same utility of binding FLNA and inhibiting cell motility and inflammation.
The claim sets differ because the reference claims do not expressly teach RAGE, TLR2 or treating hypotensive shock.
Barbier teaches a method of reducing one or both of inflammation and pain in a host mammal by administering a composition containing a compound of Formula A
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such as
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(C0105M) and
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(C0114M) (or a pharmaceutically acceptable salt thereof). See Barbier, Claim 21 and Claim 46; see also 0312. The compound binds to filamin A (FLNA). See 0002, 00023. FLNA controls cell motility by controlling the cycle of actin polymerization and depolymerization, allowing cells to move and to migrate. As actin depolymerization is linked to the inflammatory response, binding to FLNA suppresses inflammation by slowing actin polymerization and cell motility. See Barbier, 0004. Femtomolar amounts of compounds known to bind FLNA (naloxone and its inactive isomer) have been shown to reduce the microglial inflammatory response, i.e., pro-inflammatory factors and reactive oxygen species, of lipopolysaccharide -activated microglial cells. See 0004.
It was already known that microglial cells are immune cells with TLR2 and RAGE receptors. Han teaches microglia are the immune effector cells of the central nervous system (CNS) after being activated. Microglia are involved in brain diseases such as brain injury, inflammation, multiple sclerosis, Alzheimer’s disease and recurrent seizures. Appropriate inhibition of microglial cell activation at the early stage can reduce the pathological damages caused by its activation. See 1st par., p. 57. Microglial cells express RAGE and TLR2 and have an increased expression of RAGE, TLR2, and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 when activated. See p. 62-64; see figures; and ‘Discussion’ at pp. 65-67.
Strela teaches that LPS activates TLR4 in vascular smooth muscle cells, upregulating pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and impairing contractility in hypotensive septicemia, i.e., hypotensive shock. See ‘Introduction’ at p. 1-2; see title and abstract also.
A person of ordinary skill in the art (POSA) would have found it obvious to treat hypotensive shock by inhibiting immune response mediated by RAGE, TLR2, and TLRZ4 using a FLNA-binding compound such as
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(C0105M) and
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(C0114M) because Han teaches these receptors mediate LPS-induced pro-inflammatory cytokines in microglial cells and Strela teaches these same cytokines induce vascular smooth muscle dysfunction in hypotensive septic shock while Barbier teaches FLNA-binding compounds suppress inflammation. The POSA would have reasonably expected FLNA-binding compounds, including C0105M and C0114M, to inhibit microglial activity. Because these compounds exhibit anti-inflammatory efficacy against LPS-induced cytokine release, they would be expected to block the microglial activation driven by RAGE and TLR2 overexpression. In turn, this prevents the downstream surge of pro-inflammatory cytokines – such as TNF-α, IL-1β, and IL-6 – that are known to induce hypotensive septicemia.
Claim 3 limits Claims 1, wherein said compound or pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition, wherein the compound is dissolved or dispersed in a pharmaceutically acceptable diluent. Barbier teaches effective amount of a compounds of the invention may be dissolved or dispersed in a physiologically tolerable carrier. See Claim 43.
Claim 21 limits Claim 1, wherein said administration is carried out a plurality of times. Claim 22 limits Claim 1, wherein said administration is carried out daily. Claim 23 limits Claim 22, wherein said administration is carried out multiple times daily. Barbier teaches that the compounds of Formula A may be administered in a composition a plurality of times over a period of days (see Claim 48) or a plurality of times in one day (see Claim 49).
Claim 27 and Claim 28 narrow the structure to
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and
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(C0114M), respectively. Barbier teaches both C0105M and C0114M. See Claim 21 and Claim 46 for C0105M; see 0312 for C0114M.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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, James H. Alstrum-Acevedo can be reached on (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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