DETAILED ACTION
Claims 1, 3, 9-11, 14, 17-19, 23-29 are currently pending. Claims 1, 9-11, 14, 17, 19, 24-26 are currently under examination.
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 .
Withdrawn Rejections
The prior rejection of claim(s) 1-2, 7-8, 17 and 19 under 35 U.S.C. 103 as being unpatentable over WO 2006/135479 is withdrawn in light of Applicant amending instant claim 1 to specify the PHDi is 1,4-DPCA that the ‘479 publication does not teach.
Election/Restrictions
Claims 9-11 are rejoined based on Applicant’s claim amendments. Applicant has elected the single species of small molecules of proline hydrolase inhibitor (PHDi) compound 1,4 dihydrophenonthrolin-4-one-3-carboylic acid (1,4-DPCA). Applicant has amended claims 9-11 to define an additional agent and thus have been rejoined.
Examiner’s Note
Applicant's amendments and arguments filed 07/17/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 07/17/2025, it is noted that claims 1, 14, 17, 19 and 24-26 have been amended and no new matter or claims have been added.
New Rejections:
The following rejections are newly applied based on Applicant’s claim amendments.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 24 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1 is directed to wherein the agent is a small molecule prolyl hydroxylase inhibitor compound (PHDi), wherein the PHDi is 1,4-DPCA. Claim 24, which depends from claim 1, contains the limitation of “small molecule prolyl hydroxylase inhibitor agents are attached…”. Instant claim 1 is limited specifically 1,4-DPCA and does not allow for multiple PHDi, thus claim 24 is broader than instant claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Modified Rejection:
The following rejections have been modified based on Applicant’s claim amendments.
Claim(s) 1, 14, 17, 19 and 24-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0226500 (previously applied) in view of US 2015/0320877 (previously applied), US 4,506,672 (previously applied) and US 5,091,176 (preciously applied).
Regarding claim 1, the limitation of a compristion comprising a wound closure material physically or chemically associated with an agent that reduces scarring and improves the integrity of skin and underlying tissue in a mammalian subject is met by the ‘500 publication teaching sutures used in combination with anti-scarring agents to inhibit fibrosis between sutures and the hose tissue. Compositions are described for use in reducing excessive scarring and surgical adhesion (abstract). The anti-scarring agents can be used by coating or dipping the suture into the solution containing the therapeutic composition ([0697], [0757]) thus teaching physical association. Additionally, the therapeutic composition is taught as covalently linked to the suture material [0798].
Regarding claim 2, the limitation of wherein the agent blocks or inhibits the proline hydroxylase pathway or inhibits any protein in the HIF regulatory pathway is met by the ‘500 publication teaching the fibrosis inhibiting compound is propyl hydroxylase inhibits or HIF agonist from Fibrogen ([0490]-[0492]).
Regarding claim 14, the limitation of wherein the wound closure material is a suture, which is catgut protein suture is met by the ‘500 publication teaching exemplary absorbable sutures include catgut [0802].
Regarding claim 17, the limitation of wherein the wound closure material is dissolvable and wherein the material releases the agent as the material dissolves in situ is met by the ‘500 publication teaching absorbable sutures include catgut, wherein the sutures are absorbable [0802]. The suture is taught to release the agent as the suture dissolves ([0050], [0864]).
Regarding claim 26, the limitation of wherein the agent is infused into the wound closure material during generation of the material is met by the ‘500 publication teaching the anti-scarring agents used in making the sutures as a dipping solution [0697].
The ‘500 publication does not specifically teach proline hydroxylase inhibitor compound specifically 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA) (claims 7-8).
The ‘877 publication teaches compositions for enhancing tissue regeneration or wound repair in mammalian subject comprising proline hydroxylase inhibitor and a carrier composition that is a hydrogel (abstract). The composition being administered is taught to include 1,4-DPCA [0010]. The proline hydroxylase inhibitor/HIF1a increasing drug component is present in the composition in an amount that is at least partially sufficient to produce a regenerative response in the cells of the cellular medium. The contacting step can occur for a time at least partially sufficient to produce a regenerative response [0026]. The therapeutic compound comprising at least one 1,4-DPCA moiety coupled to via a cleavable (e.g. without limitation, hydrolysable) moiety to a polymer component such as a poly(alkylene oxide) component. The compound can comprise such a copolymer coupled to the terminus to a 1,4-DPCA moiety [0043]. 1,4 DPCA and PHDs is inhibition of collagen hydroxylation leading to reduced scarring and increased degradation [0080]. The composition is taught as implantable [0090].
The combination of references does not specifically teach wherein the chemical association is covalent formed between the agent and the wound closure material (claim 19).
The combination of references wherein the wound closure material is a catgut suture having multiple amino acid side chains to which small molecule or peptide agents are attached via covalently bonds (claim 24) to which 1,4-DPCA molecular are attached via covalent bonds (claims 25).
The ‘672 patent teaches catgut suturing filament that contains a coating on the catgut filament with isocyanate capped polyhydroxylated polyesters (abstract). The sheath is bonded to the catgut core by urea or urethane links wherein the bond is a covalent bond (claims 9-10) wherein the polyesters are taught to include hydroxyl groups and diacids (claims 1-7).
The ‘176 patent teaches biocompatible polymer derived from isocyanate capped high molecular weight are covalently linked to drugs. The polymer modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, long dime residence time in circulation and enhanced potency of the drug (abstract). Covalently binding the drugs to hydrophilic isocyanate end capped prepolymers with having isocyanate-reactive groups such as hydroxyl and carboxyl groups. The enhanced biological and pharmacological activities of the polymer-modified drugs include increased circulating half-life, decreased immunogenicity and increased potency (column 1, lines 10-25).
It would have been obvious to one of ordinary skill in the art to substitute a first anti-scarring agent as taught by the ‘500 patent with a second anti-scarring agent, i.e., 1,4-DPCA moiety, as taught by the ‘877 publication with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use 1,4 DPCA as taught by the ‘877 publication on the sutures taught by the ‘500 publication because the ‘500 publication teaches the use of antiscarring agents and the ‘877 publication teaches 1,4-DPCA reduces scarring. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use 1,4-DPCA on the sutures of the ‘500 publication as the ‘500 publication teaches the use of anti-scarring agents prolyl hydroxylase inhibitors including HIF agonist and the ‘877 publication teaches the use of a specific combination of the proline hydroxylase inhibitor/HIF1a increasing drug component is present in the composition in an amount that is at least partially sufficient to produce a regenerative response in the cells of the cellular medium, thus teaching it is known to use HIG agonists and PHI inhibitors in combination for anti-scarring wherein the ‘500 publication teaches the desire for anti-scarring.
It would have been prima facie obvious to one ordinary skill in the art before the filing date of the claimed invention to covalently attach the anti-scarring agent to the suture taught by the combination of the ‘500 publication and the ‘877 publication using isocyanate compound as the ‘672 patent teaches that it is known to bond acid function a groups to catgut sutures using isocyanate compounds and the ‘176 patent teaches bonding drugs polymers using isocyanate compounds. One of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation of success as the ‘877 publication teaches 1,4 DPCA containing a carboxylic acid group and the ‘176 publication teaches isocyanate compounds bound to COOH groups of active agent and the ‘672 publication teaches isocyanate groups bound to catgut sutures thus teaching that it was known to use isocyanate groups to bond to active agents and isocyanate groups are taught to bond active agents to catgut sutures. One of ordinary skill in the art before the effect filing date of the claimed invention would be motivated to bond the anti-scarring agent to the catgut suture because the ‘500 publication teaches the therapeutic composition is taught as covalently linked to the suture material [0798] and the ‘176 patent teaches the enhanced biological and pharmacological activities of the polymer-modified drugs include increased circulating half-life, decreased immunogenicity and increased potency.
Claim(s) 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0226500, US 2015/0320877, US 4,506,672 and US 5,091,176 as applied to claims 1, 14, 17, 19 and 24-26 above, and further in view of WO 2013/119551 (Applicant provided).
As mentioned in the above 103(a) rejection, all of the limitations of claims 1, 14, 17, 19 and 24-26 are taught by the combination of the ‘500 publication, the ‘877 publication, the ‘672 patent and the ‘176 patent.
The combination of references does not specifically teach further comprising an additional agent which is a protein or peptide such as PAR1 agonist (claims 9-10) and additional agent which is DNA or RNA sequences of an siRNA or a miRNA (claim 11).
The ‘551 publication teaches compositions related to wound healing e.g. repair of wounds and/or tissue defects (abstract). The fibers are taught to include silk fibroin and chitin. The compristion may further include an agent [0006]. The therapeutic agent can include DNA, RNA, siRNA, viruses, anti-inflammatory agents [0058]. The composition may further include hemostatic agents such as thrombin [0063], wherein the instant specification teaches PAR1 agonist is thrombin (page 11, last paragraph to page 12, first paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to include siRNA and thrombin in the sutures taught by the ‘500 publication because the ‘551 publication teaches that it was known to include siRNA and thrombin on fibers for wound healing. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘500 publication teaches sutures comprising anti-scarring agents using various therapeutic agents and the ‘551 publication teaches active agents to be used on fibers for wound healing. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use siRNA and thrombin as additionally agents on the sutures taught by the ‘500 publication because the ‘551 publication teaches thrombin is a hemostatic agent and siRNA can be further agents included on fibers for wound healing and the ‘500 publication teaches the sutures to be used for wound healing without scaring ([0016], [0051]).
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
Applicant argues in the response to Restriction Requirement applicant elected wound-closure material is suture and did not specifically elect “cat gut suture” and as amended recite the suture corpses an additional agent in addition to the PHDI, claim 9-11 do not recite a separate and apart from the elected PHDI and are encompassed by the species election. Further the linkers recited in claim 23 are encompassed by the election of covalently linking the material with the agent.
In response, in the reply filed 11/15/2024 Applicant specifically elected 1) the material has multiple amino acid side chains to which the agent molecules are attached via covalently bonds (claims 24-25), 2) PHDI compound is 1,4-dihydrophenonthrolin-4-one-3-carbcy acid (1,4-DPCA) and 3) the wound closure material is a cat gut suture. Thus Applicant has specifically elected cat gut suture. Amended claims 9-11 to include additional ingredients, and thus are rejoined based on Applicant’s claim amendments.
103:
Applicant argues the ‘500 publication teaches over 100 pages and recites over 250 classes of agents but does not teach 1,4-DPCA whatsoever. The ‘877 publication teaches a drug delivery system wherein1,4-DPCA is a drug component as part of a hydrogel, not a suture. None of the cited reference disclose compositions comprising a wound-closure material associated with an agent that is a small molecule proline hydrolase inhibit, including 1,4-DPCA. Applicant argues impermissible hindsight.
In response, the ‘500 publication teaching sutures used in combination with anti-scarring agents to inhibit fibrosis between sutures and those tissue. Compositions are described for use in reducing excessive scarring and surgical adhesion (abstract). The anti-scarring agents can be used by coating or dipping the suture into the solution containing the therapeutic composition ([0697], [0757]) thus teaching physical association. Additionally, the therapeutic composition is taught as covalently linked to the suture material [0798]. The ‘500 publication teaching the fibrosis inhibiting compound is propyl hydroxylase inhibits or HIF agonist from Fibrogen ([0490]-[0492]). The ‘877 publication teaches compositions for enhancing tissue regeneration or wound repair in mammalian subject comprising proline hydroxylase inhibitor and a carrier composition that is a hydrogel (abstract). The composition being administered is taught to include 1,4-DPCA [0010]. The proline hydroxylase inhibitor/HIF1a increasing drug component is present in the composition in an amount that is at least partially sufficient to produce a regenerative response in the cells of the cellular medium. 1,4 DPCA and PHDs is inhibition of collagen hydroxylation leading to reduced scarring and increased degradation [0080]. The composition is taught as implantable [0090]. Thus the ‘500 publication teaches the desire to prevent scarring and the ‘877 publication teaches 1,4 DPCA PHDs is inhibition of collagen hydroxylation leading to reduced scarring and increased degradation [0080]. This is not hindsight reasoning and motivation is found in the prior art.
Applicant argues there is no teaching or suggestion in either the ‘672 or ‘176 patent of 1,4-DPCA no teaching of covalently linking.
In response, the ‘500 publication teaches the desire for the antiscarring agent to be covalently bound to the suture material [0798]. The ‘672 patent teaches catgut suturing filament that contains a coating on the catgut filament with isocyanate capped polyhydroxylated polyesters (abstract). The sheath is bonded to the catgut core by urea or urethane links wherein the bond is a covalent bond (claims 9-10) wherein the polyesters are taught to include hydroxyl groups and diacids (claims 1-7). The ‘176 patent teaches biocompatible polymer derived from isocyanate capped high molecular weight are covalently linked to drugs. The polymer modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, long dime residence time in circulation and enhanced potency of the drug (abstract). Covalently binding the drugs to hydrophilic isocyanate end capped prepolymers with having isocyanate-reactive groups such as hydroxyl and carboxyl groups. The enhanced biological and pharmacological activities of the polymer-modified drugs include increased circulating half-life, decreased immunogenicity and increased potency (column 1, lines 10-25). One of ordinary skill in the art would have been motivated to covalently link the antiscarring agent to the suture based on the teachings of the ‘500 publication, wherein the 1,4-DPCA is rendered obvious as discussed above. It would have been prima facie obvious to one ordinary skill in the art before the filing date of the claimed invention to covalently attach the anti-scarring agent to the suture taught by the combination of the ‘500 publication and the ‘877 publication using isocyanate compound as the ‘672 patent teaches that it is known to bond acid function a groups to catgut sutures using isocyanate compounds and the ‘176 patent teaches bonding drugs polymers using isocyanate compounds. One of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation of success as the ‘877 publication teaches 1,4 DPCA containing a carboxylic acid group and the ‘176 publication teaches isocyanate compounds bound to COOH groups of active agent and the ‘672 publication teaches isocyanate groups bound to catgut sutures thus teaching that it was known to use isocyanate groups to bond to active agents and isocyanate groups are taught to bond active agents to catgut sutures.
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.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613