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 Claims
Claims 1 and 8-10 are pending. Claims 2-7 are canceled. Claim 1 is amended.
Claims 1 and 8-10 are examined on their merits in view of the elected species of chitosan and substance P.
Previous Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.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.
Rejections Withdrawn
Claim Rejections - 35 USC § 103
In light of the amendments to the claims the rejection of claims 1 and 8-10 under 35 U.S.C. 103 as being unpatentable over KR 20150006223 (1/16/2015)(5/20/2022 IDS)(“KR 2013”) in view of KR20190040757 (10/11/2017)(2/22/2024 IDS)(“KR 2019”), Kumar et al. US 9526762 (12/27/2016) and KR 20130114968 (10/21/2013) (“KR 2013”) as evidenced by the specification is withdrawn.
New Rejections
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over KR 20150006223 (1/16/2015)(5/20/2022 IDS)(“KR 2013”) in view of KR20190040757 (10/11/2017)(2/22/2024 IDS)(“KR 2019”), Kumar et al. US 9526762 (12/27/2016), KR 20130114968 (10/21/2013) (“KR 2013”) and Pouyani et al. US 5652347 (7/29/1997) as evidenced by the specification.
KR2015 teaches a hydrogel prepared by mixing a cationic substance and an anionic substance by electrostatic attraction and a process for producing the hydrogel. (See Abstract). KR 2015 teaches the adding of an anionic substance to a solvent to form a solution. (See KR2015 pages 1-2 and claim 1.) KR 2015 teaches the adding of a cationic substance to a solvent to form a solution and then mixing the solution containing the anionic substance with the solution containing the cationic substance to form a hydrogel by virtue of crosslinking due to electrostatic attraction force as called for in instant claim 1. (See KR2015 pages 1-2 and claim 1.)
KR2015 teaches that the anionic substance can be hyaluronic acid and the cationic substance can be chitosan. (See Figure 8). Hyaluronic acid is called for in instant claim 1. Chitosan is called for in instant claim 1. A first solution that comprises hyaluronic acid is called for in claim 1 as well. A second solution that comprises chitosan is called for in claim 1 as well. KR2015 teaches a hydrogel formed from chitosan and hyaluronic acid by electrostatic attraction. (See Figure 8). KR 2015 teaches that the hydrogel can be used as an injectable hydrogel. KR 2015 thus teaches an injectable hydrogel as called for in instant claims 9 and 10.
KR2015 teaches that the first solution containing the hyaluronic acid is mixed with the second solution containing the chitosan in a volume ratio of 99:1 to 1 to 99 and are preferably mixed at an equal volume, so a 1:1 ratio is preferred. (See final paragraph on page 5). A 1:1 ratio falls within the 2:1 to 1:2 called for in instant claim 1.
KR2015 does not teach a vascular endothelial cell growth mimetic peptide having the amino acid sequence of SEQ ID No. 1. KR2015 does not teach a vascular endothelial growth factor mimetic peptide being introduced through a carboxylic acid functional group and does not teach its preparation by reacting the vascular differentiation inducing factor and anionic hyaluronic acid in which a carboxylic acid functional group is activated. KR2015 also does not teach substance P. These deficiencies are made up for with KR2013, KR 2019, Kumar et al. and Pouyani et al.
KR2013 teaches a polypeptide with stem cell recruiting activity that can enable effective angiogenesis and tissue regeneration, thus being able to be used as therapeutic agent for treating ischemic diseases. (See Abstract). KR2013 teaches that in its polypeptide having stem cell recruiting activity, substance P is peptide-bonded to a self-assembled peptide. KR2013 teaches that its composition is a synthetic biomaterial that is composed of a hydrogel type fibrin such as chitosan that can be used as a biodegradeable polymer injection type that can repair a certain volume of a wound. (See page 2, 7th paragraph). Substance P is called for in instant claim 1 and it is a stem cell recruitment factor as called for in instant claim 1. KR 2013 teaches that substance P allows for the enhancement of stem cell mobilization activity. (See page 6).
With respect to claim 9’s language of “for tissue regeneration” this is language of intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, as it is in this instance, then it meets the claim.
With respect to claim 10’s language of “for fillers” this is language of intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, as it is in this instance, then it meets the claim.
KR2019 teaches a natural biomaterial and a growth factor mimetic protein introduced through a carboxyl group. (See Abstract and claim 1) KR teaches a method of making the biomaterial in which a first liquid is prepared by introducing a first chemical containing substance into a solution which contains a biomaterial. (See KR claim 5a). The biomaterial of this first solution can be hyaluronic acid. (See Fig. 2 and Experimental Example 6) A second liquid is then prepared which has a second natural biological material in a solution and a second growth factor mimetic protein is introduced and then the first and second liquid are chemically bonded to form a hydrogel. (See KR claim 5).
KR2019 describes the growth factor mimetic protein being introduced through a carboxylic acid functional group. (See KR claim 1 and [0005] on page 1). KR thus teaches that the vascular differentiation inducing factor and hyaluronic acid react via a carboxylic acid functional group as called for in instant claim 4. KR 2019 teaches a hydrogel with a polypeptide with stem cell recruiting activity that can enable effective angiogenesis and tissue regeneration, thus being able to be used a therapeutic agent for treating ischemic diseases. (See Abstract).
Kumar et al. (Kumar) teaches multidomain peptides capable of self-assembly into a nanofibrous hydrogel structure capable of stimulating a robust angiogenesis response. (See Abstract). Kumar discloses Seq ID No. 1: Lys Leu Thr Trp Gln Glu Leu Tyr Gln Leu Lys Tyr Lys Gly Ile (See Kumar Sequence Listing and Table 1). Kumar teaches that its composition containing its disclosed peptides can treat various diseases or condition by administering the composition to a human who has suffered an ischemic wound to promote neovascularization and angiogenesis thereby enhancing healing. (See col. 7, lines 44-56). Seq ID No. 1 is called for in instant claim 1 and it is a vascular endothelial cell growth factor mimic peptide as called for in instant claim 1.
Pouyani et al. teaches a method for producing hyaluronate functionalized with dihydrazide that includes mixing hyaluronate and hihydrazide in aqueous solution then adding carbodiimide so that the hyaluronate and dihydrazide react to form functionalized hyluronate. (See Abstract). Pouyani teaches that the hydrazido-functionalized hyaluronic acid can be crosslinked to form hydrogels. (See col. 8).
Pouvani teaches that the functionalized HA or crosslinked HA may be used as a carrier for a wide variety of releasable biologically active substances including growth factors, etc. (See col. 11). The cross-linked hyaluronate derivatives are pore containing matrices wherein biologically active compounds such as peptides, growth factors, etc. can be physically or chemically incorporated. (See col. 12-13). Peptides are a preferred biologically active substances. (See col. 11).
It would be prima facie obvious before the earliest effective filing date for one of ordinary skill in the art making the KR 2015 hydrogel of electrostatically attracted hyaluronic acid and chitosan to introduce peptide of Seq ID No. 1 taught by Kumar to the carboxylic acid functionality of the hyaluronic acid as taught by KR2019 in order to have a hydrogel with a peptide with stem cell recruiting activity that can enable effective angiogenesis and tissue regeneration, thus being able to be used a therapeutic agent for treating ischemic diseases as taught by KR 2019.
It would be prima facie obvious before the earliest effective filing date for one of ordinary skill in the art making the KR 2015 hydrogel to introduce peptide of Seq ID No. 1 taught by Kumar to the carboxylic acid functionality of the hyaluronic acid as taught by KR2019 using the preparation process taught in Pouyani of reacting the vascular differentiation inducing factor and anionic hyaluronic acid in light of Pouyani’s teaching that the hyaluronic acid can be used as a carrier for chemically incorporated peptides which are taught to be a preferred biologically active substances. There would be a reasonable expectation of success because peptide are taught in Pouvani to be a preferred biologically active substance for the hyaluronic acid.
It would be prima facie obvious before the earliest effective filing date for one of ordinary skill in the art making the KR 2015 hydrogel of electrostatically attracted hyaluronic acid and chitosan to also bind substance P taught by KR 2013 to the peptide of Seq ID No. 1 in order to have a hydrogel with enhanced stem cell recruiting activity as taught by KR 2013. There would be a reasonable expectation of success because KR 2013 teaches that substance P can be bonded to a peptide.
With respect to the storage modulus in claim 8, and the recruitment of endogenous progenitors or stem cells and the induction of vascular differentiation of recruited cells of claim 1, the prior art is silent as to these properties. The prior art of the combined teachings of KR2015 in view of KR2019, Kumar and KR2013, however, teaches all of the claimed components in the same amounts (at the overlap of the ranges). KR2015 in view of KR2019, Kumar and KR2013 teaches an injectable hydrogel that consists of a hydrogel formed by the electrostatic attraction of hyaluronic acid to chitosan containing substance P wherein Seq ID No. 1 is connected to the hyaluronic acid via a carboxylic acid functionality.
As evidenced by Figure 5 of the instant specification, the combination of HA and CH (cationic chitosan and HA) result in a storage modulus between 1-100 Pa. Since KR2015, KR2013, Kumar and KR2019 arrive at an identical composition comprising hyaluronic acid and cationic chitosan, the storage modulus properties would necessarily be the same.
This composition would also necessarily recruit of endogenous progenitors or stem cells and the induction of vascular differentiation of recruited cells as evidenced by the specification at [007] and [0021] and Figure 1.
A composition having the same components as those claimed will necessarily have the same properties as those claimed, See MPEP 2112.01[R-3]: “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” In re Spada, 911 F2d 705, 709, 15 USQPQ2d 1655, 1658 (Fed. Cir. 1990).
Response to Arguments
Applicants’ comments on March 27, 2026 have been fully considered and are found to be unpersuasive for the reasons described below.
Applicants note the amendments to the claims. It appears that support can be found in the claims as originally filed and in paragraph [0065] of the specification.
Applicants maintain that the cited references individually or in combination do not make out a prima facie case of obviousness in that they fail to teach the claimed injectable hydrogel composition and they do not provide a person of ordinary skill in the art any reason motivation to combine the references to arrive at such a composition.
Applicants assert that KR2019 does not teach that incorporating the recited vascular endothelial growth mimetic peptide, stem cell recruitment factor and the recited hydrogel as formed, together in an injectable hydrogel would be achievable with a reasonable expectation of success, let alone with the dramatic effect shown in the Examples.
Kumar teaches the sequence of DEQ ID No. 1. However, Kumar does not teach or suggest preparing a first solution by reacting the vascular differentiation inducing factor and anionic hyaluronic acid in which a carboxylic acid functional group is activated.
KR 2013 is cited for allegedly teaching a polypeptide with stem cell recruiting activity but does not teach or suggest preparing a first solution by reacting the vascular differentiation inducing factor and anionic hyaluronic acid in which a carboxylic acid functional group is activated.
Applicants also assert that the invention demonstrates unexpected results.
Specifically, Applicants assert that the data in the specification demonstrates that chemically introducing vascular endothelial growth factor mimetic peptide (VP) into HA in combination with an exemplary stem cell recruitment factor enhances the angiogenic response in a manner that would not have been reasonably expected based on the cited references. This is compared to the case where only the VP and the hydrogel are mixed, which is prepared by including the stem cell recruitment factor as an additional component as well as chemically linking the hydrogel and the VP results in increased stem cell recruitment and vascular differentiation at a level that would not have been expected or predicted by a skilled artisan based on the cited references.
In light of the amendments to the claims, Applicants argument that the cited references do not teach a preparation process of reacting the vascular differentiation inducing factor and anionic hyaluronic acid is found to be persuasive and a new rejection is applied above.
As described in the new rejection above, it would be prima facie obvious before the earliest effective filing date for one of ordinary skill in the art making the KR 2015 hydrogel of electrostatically attracted hyaluronic acid and chitosan to introduce peptide of Seq ID No. 1 taught by Kumar to the carboxylic acid functionality of the hyaluronic acid as taught by KR2019 in order to have a hydrogel with a peptide with stem cell recruiting activity that can enable effective angiogenesis and tissue regeneration, thus being able to be used a therapeutic agent for treating ischemic diseases as taught by KR 2019.
It would be prima facie obvious before the earliest effective filing date for one of ordinary skill in the art making the KR 2015 hydrogel to introduce peptide of Seq ID No. 1 taught by Kumar to the carboxylic acid functionality of the hyaluronic acid as taught by KR2019 using the preparation process taught in Pouyani of reacting the vascular differentiation inducing factor and anionic hyaluronic acid in light of Pouyani’s teaching that the hyaluronic acid can be used as a carrier for chemically incorporated peptides which are taught to be a preferred biologically active substances. There would be a reasonable expectation of success because peptide are taught in Pouvani to be a preferred biologically active substance for the hyaluronic acid.
Applicants assertion of unexpected results is not found to be persuasive, however. It should be noted that the property of powerful stem cell recruiting activity that can enable effective angiogenesis and tissue regeneration, thus being able to be used a therapeutic agent for treating ischemic diseases is taught in KR2019. KR 2019 teaches a hydrogel with a polypeptide with stem cell recruiting activity that can enable angiogenesis and tissue regeneration. KR2019 describes the growth factor mimetic protein being introduced through a carboxylic acid functional group. (See KR claim 1 and [0005] on page 1). KR thus teaches that the vascular differentiation inducing factor and hyaluronic acid chemical reaction via a carboxylic acid functional group to chemically link the two entities. Therefore, the properties appear to be expected and expressly suggested by the prior art.
See MPEP 716.02(e). The teachings of the prior art are consistent with expected beneficial results. Expected beneficial results are more indicative of obviousness than of unobviousness. “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F2d 535, 538, 152 USPQ 602, 604 (CCPA 1967)(resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentrifice was expected based on the teaching of the prior art). Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). MPEP 716.02(c).
The submission of objective evidence of patentability does not mandate a conclusion of patentability in and of itself. In re Chupp, 816 F.2d 643, 2 USPQ2d 1437 (Fed. Cir. 1987). Facts established by rebuttal evidence must be evaluated along with the facts on which the conclusion of a prima facie case was reached, not against the conclusion itself. In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990). MPEP 716.01(d).
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 SARAH CHICKOS whose telephone number is (571)270-3884. The examiner can normally be reached on M-F 9-6.
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SARAH CHICKOS
Examiner
Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
Prosecution Insights