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 the Claims
Claims 1-3, 13-20 and 22 are pending in a response of 04/13/2026.
Withdrawn rejections:
Applicant's amendments and arguments filed 04/13/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
The following rejection and/or objection are either reiterated or newly applied. They constitute the complete set of rejection and/or objection presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 depends from canceled claim 12. No claim depends from a canceled claim because it is not clear which claim it is supposed to depend from.
Appropriate correction is requested.
New Grounds of Rejection --- as necessitated by amendment
Claim Rejections - 35 USC §103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
As indicated above, the present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-3, 13-20 and 22 are rejected under 35 USC 103 as being obvious over Gravett et al. (US2014/0328926A1) in view of Kuo et al., “Chemical modification of hyaluronic acid by carbodiimide”, Bioconjugate Chem. 1991, vol. 2, pp. 232-241. Xu et al., “Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks”, Soft Matter, 2012, vol. 8, pp. 3280-3294.
Applicant claims including the below claim 1 filed on 04/13/2026:
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Determination of the scope and content of the prior art
(MPEP 2141.01)
Gravett teaches that hydrophilic/water soluble hydrogel composition is formed by reaction (2-(vinylsulfonyl)ethoxy)1-10%hyaluronic acid (HA) with a thiol crosslinker having two or more thiol groups (e.g.,. [0009], Example 2 and claim 1 of prior art) which reads on the claimed hydrogel containing one HA derivative and thiol crosslinker, and vinylsulfonyl reads on the claimed modification; 2-(vinylsulfonyl)ethoxy)1-10%hyaluronic acid (HA) has a molecular weight ranging from about 700 to about 3 million Daltons (e.g., [0008] and [0111]) and the reaction time depends on degree of modification ranging from 4-20% (e.g., Table 1 – [0165]); the said crosslinker includes crosslinker having thiol (e.g., PEG-dithiol) or acrylate group (e.g., [0113]); the HA aqueous solution is added to the hydrogel in an amount of about 0.3% (=3mg/ml) to about 4% (=40mg/ml) ([0132]) or from about 0.5% (=5mg/ml) to about 2% (=20mg/ml) or at least 0.1mg/ml ([0134]), and final HA content in the hydrogel composition is about 0.05 to 5% (=0.5mg/ml to 50mg/ml) ([0132]) which overlaps the claimed range of about 0.3 to about 5 mg/ml and relative amounts of hyaluronic acid to crosslinked (e.g., (2-vinylsulfonyl)ethoxy)hyaluronic acid/PEG-dithiol) hydrogel particles in the composition fall within a range from about 10:1, or about 5:1 or about 3:1 or about 1:1 (see entire document including e.g., claims 1, 5 and 8, [0084], [0113], [0132], and Example 8 of prior art). MPEP 2144.05 states that [I]n the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); the said reaction reads on the claimed condition enabling formation of the hydrogel of instant claim 19; and the hydrogel containing HA or its derivatives are used in tissue engineering, wound healing, etc. (e.g., [0003], [0058], [0067])(instant claims 1 & 17-20 (in part); and claims 2, 3 & 13-16).
However, Gravett does not expressly teach intrinsic viscosity of hydrogel forming polymer (e.g., HA) of instant claims 1, 17, 20 and 22. The deficiency is cured by Xu and Kuo.
Xu discloses hyaluronic acid (HA)-based hydrogels are effective for tissue repair and regeneration (abstract); and HA-based hydrogels can be obtained by varying molecular weight, the degree of modification, and the concentration of the reactive HA precursors (page 3281, right column).
Kuo discloses sodium hyaluronic acid (HA) having a molecular weight of e.g., 1 million possesses intrinsic viscosity of 3000 mL/g (=30 dL/g) which absorbs water, cushions cells, and lubricates the soft tissue of joints (page 232, left column, first para.); chemical modification of HA with vinyl sulfone, formaldehyde, which modifications have been used to crosslink HA to produce highly swollen gels (=hydrogel) wherein the said intrinsic viscosity overlaps the instant range of at least 3dL/g or 20dL/g; and such chemically modified HA is thought to have surgical and medical value as long-lasting biomaterials, and as potential drug delivery vehicles (page 232, left column, second paragraph); HA has 1.5 to 2 million molecular weight (page 233, first para.); in particular crosslinking of NaHA with biscarbodiimide has been useful as potential candidates for replacement of soft tissue or for other biomedical applications (page 239, right column, section “crosslinking of NaHA with Biscarbodiimides); NaHA cross-linking with aromatic biscarbodiimide was performed at two molar equivalent ratios of the biscarbodiimides and HA being 0.1-0.18, and crosslinked HA showed gel-like properties in which gel could be diluted to 0.5mg/mL for intrinsic viscosity measurement (page 240, second para.) and intrinsic viscosity of NaHA/carbodiimide has 2866mL/g (=28.66 dL/g), 2730 ml/g (27.30dL/g), 2534mL/g (=25.34dL/g), etc. (page 235, e.g., HA derivatives 7a, 7b, 4a, 4b, 4c, 11a, 11b, etc.) which overlaps the instant range of at least 3dL/g. For the overlapping ranges, please see MPEP2144.05 noted above. And the carbodiimide-modified NaHA suggests that such chemical modification has altered the conformational structure of NaHA to a more rigid and extended one, thus increasing the hydrohynamic volume of the macromolecules (see page 240, right column, conclusion).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
1. The difference between the instant application and Gravett is that Gravett does not expressly teach intrinsic viscosity of hydrogel forming polymer of instant claims 1, 17, 20 and 22. The deficiency is cured by Xu and Kuo.
2. Gravett in view of Xu and Kuo do not expressly teach the claimed rheological properties of complex viscosity/storage & loss modulus/ yield strain of instant claims 1 and 18-20.
Level of Ordinary Skill in the Art
(MPEP 2141.03)
The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The examiner must ascertain what would have been obvious to one of ordinary skill in the art at the time the invention was made, and not to the inventor, a judge, a layman, those skilled in remote arts, or to geniuses in the art at hand. Environmental Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 218 USPQ 865 (Fed. Cir. 1983), cert. denied, 464 U.S. 1043 (1984).
The level of ordinary skill will often predetermine whether an implicit suggestion exists to modify the prior art. Persons of varying degrees of skill not only possess varying bases of knowledge, they also possess varying levels of imagination and ingenuity in the relevant field, particularly with respect to problem-solving abilities. If the level of skill is low, for example that of a mere technician, then it may be rational to assume that such an artisan would not think to combine references absent explicit direction in a prior art reference. If, however, the level of skill is that of a relevant research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from medical, pharmacy, physiology and chemistry— without being told to do so.
Indeed, MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). This is because “The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the time of the invention.” (MPEP 2141.03(1)) and an artisan must be presumed to know something about the art apart from what the references disclose. See In re Jacoby, 309 F.2d 513, 516 (CCPA 1962). “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418, 82 USPQ2d at 1396. (MPEP 2141.03 (I)). “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07). In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(11)).
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of the skilled in the art to further define hydrogel forming polymer such as modified hyaluronic acid (HA) of Gravett with higher intrinsic viscosity as taught by Xu/Kuo or to select certain intrinsic viscosity of Xu/Kuo for forming intended hydrogel used in medical tissue/wound engineering field.
One of the skilled in the art would have been motivated to do so because it is well known that HA or its derivatives is useful in pharmaceuticals as taught by Gravett/ Xu/Kuo; in particular Xu discloses whether hydrogel formation with desired properties depends on molecular weight, degree of modification, concentration of HA; and Kuo teaches chemically modified HA is thought to have surgical and medical value as long-lasting biomaterials, and as potential drug delivery vehicles (page 232, left column, second paragraph of Kuo), and therefore, the significant increase of the intrinsic viscosity and the further line broadening of the NMR spectra of the carbodiimide-modified NaHA appears to suggest that such chemical modification has altered the conformational structure of NaHA to a more rigid and extended one, thus increasing the hydrodynamic volume of the macromolecules (see conclusion on page 240); thus, it would have been obvious to combine the applied references in order to enhance the properties including intrinsic properties of hydrogel containing HA derivative with more rigid extended structure useful for tissue engineering purpose, as taught by Xu/Kuo.
Gravett in view of Kuo/Xu would implicitly achieve the claimed rheological properties of complex viscosity/storage and loss modulus/ yield strain. That is, Gravett discloses hydrogel containing overlapping range of HA; Gravett/Kuo/Xu disclose overlapping molecular weight of HA or its derivative (up to 7 million Da); Kuo teaches overlapping intrinsic viscosity of HA derivatives and its significant; Xu teaches significance of chemical modification, and accordingly, instantly claimed hydrogel and its rheological properties would be implicit in the absence of evidence to the contrary and that is, those rheological properties are natural result of the combination of elements. In this regard, please see Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008). (inherency is limited when applied to obviousness and is present only when the limitation at issue is the “natural result” of the combination of prior art elements; quoting In re Oelrich, 666 F.2d 578, 581 (CCPA 1981)). See also In Sandoz Inc. v. EKR Therapeutics, LLC, IPR2015-00008, slip. op. at 6 (Apr. 24, 2015), the Board found that "Petitioner's inherency argument also fails," and cited Par for the proposition that "[(Inherency may supply a missing claim limitation in an obviousness analysis" only if "the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments have been fully considered, but moot of newly applied references. However, the Examiner would like to address the followings:
Applicant argues that Gravett teaches hydrogel formed by reaction of a HA derivatives having divinyl sulfone with thiol-functionalized HA; and the specification including the Examples demonstrated unexpected results of spreading across a surface with claimed concentration and intrinsic viscosity.
The Examiner responds that Gravett teaches one derivatives of HA (see Example 2) as noted above; the applicant did not provide a fair comparison between the claimed invention and the closest art; and instant Samples F and H form hydrogel within the claimed concentration and intrinsic viscosity (see Examples 3.2, 3.3, 4.2 and 4.4). However, Xu teaches whether the formation of hydrogel depends on molecular weight of HA or its derivative, chemical modification, concentration of HA, and Kuo teaches overlapping intrinsic viscosity of chemically modified HA derivatives, and Gravett discloses overlapping concentration and general range of molecular weight of HA or its derivative. Therefore, alleged unexpected results of rheological properties in hydrogel would be expected. See also Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008) noted above. Lastly, even data of instant Examples (Samples F and H) is not commensurate with scope of instant claim 1 because instant claim 1 does not require the molecular weight and degree of modification (DM) of HA or its derivative, while the data do.
Thus, applicant’s arguments are not persuasive.
Conclusion
All examined claims are rejected.
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 KYUNG S CHANG whose telephone number is (571)270-1392. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Yong (Brian-Yong) S Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYUNG S CHANG/Primary Examiner, Art Unit 1613
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