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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on October 2, 2025 has been entered.
Information Disclosure Statement
The IDS filed December 10, 2025 has been reviewed.
Status of Claims
Claims 1-6 and 15-28 are pending. Claims 7-14 are canceled. Claim 28 is newly added.
Claims 1-6 and 21-25 are withdrawn as being directed to a non-elected species, there being no allowable linking claim.
Claims 15-20 and 26-28 are examined on their merits.
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Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.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 objects 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Rejections Withdrawn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
Upon further consideration the rejection of claims 15-18 and 26-27 under 35 U.S.C. 103 as being unpatentable over CN 102399295 (4/4/2012)(9/8/2021 IDS) in view of JP 2007/520589 (7/26/2007) and Ren et al. CN 101759881 (6/20/2010) is withdrawn.
Upon further consideration the rejection of claims 19-20 under 35 U.S.C. 103 as being unpatentable over CN 102399295 (4/4/2012)(9/8/2021 IDS) in view of JP 2007/520589 (7/26/2007) and Ren et al. CN 101759881 (6/20/2010) as applied to claims 15-18 and 26-27 and further in view of CN 102070791 (5/25/2011) is withdrawn.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 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 15, 18 and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over CN 102399295 (4/4/2012)(9/8/2021 IDS) in view of JP 2007/520589 (7/26/2007) and Liu et al. Biocompatibility and stability of disulfide-crosslinked hyaluronan films, Biomaterials Vol. 26, Issue 23, August 2005, pp 4737-4746.
CN ‘295 teaches a low modification-biocompatible high molecular sulfhydrylation modified derivatives. While biocompatible, the in-vivo dissolubility of the derivatives is reduced, so the materials well satisfy the requirements of clinical medical applications. (See Abstract). CN ‘295 teaches a disulfide bond cross-linked hyaluronic acid sulfhydryl derivative that is a gel formed from a solution having a concentration of 5 mg/ml. (See Example 3). CN ‘295 teaches the use of the gel disulfide bond cross-linked hyaluronic acid sulfhydryl derivative to prevent adhesion between tissues. (See claim 19).
CN ‘295 teaches the use of the gel disulfide bond cross-linked hyaluronic acid sulfhydryl derivative to prevent adhesion between tissues but does not expressly teach the placing of it in the pelvis. CN ‘295 does not teach 3 mg/mL. These deficiencies are made up for with the teachings of JP 2007/520589 and Liu et al.
JP 2007/520589 “JP 2007” teaches cross-linked hyaluronic acid that is placed in a pelvis during a pelvic procedure to prevent adhesion of tissues in the pelvis. (See [0134] and [0285-287] See Example 6). The composition prevented adhesions very successfully. (See Example 6 and Figure 20). This reads on the method of reducing tissue surrounding a site of the abdominal operation by applying a gel of disulfide crosslinked hyaluronic acid to tissue surrounding a site of the abdominal operation as called for in instant claim 15. The procedure is a pelvic procedure as called for in instant claim 26. JP 2007 teaches that the prevention of tissue adhesions is described to avoid future complications. (See [0235], [0285-0287]). The composition can be a gel. (See [0096], [0254], [281]).
Liu et al. (Liu) teaches a cross-linked thiolated hyaluronic acid that is a gel formed from a solution having a concentration of 3% w/v (3 mg/mL). (See page 4738 in Materials and Methods. The 3 mg/ml content of the cross-linked hyaluronic acid falls within the from 3 to 4.5 mg/mL called for in instant claim 15 and is the actual 3 mg/mL called for in instant claim 27. Liu teaches that the cross-linked thiolated HA hydrogel prevents post-surgical adhesion formation in a rat uterine horn model. (See page 4738).
Claims 18 contains limitations regarding how the compositions are made. However, the compositions are not limited to the manipulation of the process of making the product. “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Furthermore, “[b]ecause validity is determined based on the requirement of patentability, a patent is invalid of a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” Amgen Inc. v. F. Hoffman-La Roche Ltd. 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009); Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733.
It would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the gel disulfide bond cross-linked hyaluronic acid sulfhydryl derivative of CN ‘295 to apply a gel of disulfide crosslinked hyaluronic acid to tissue surrounding a site of a pelvic procedure as taught by JP 2007 in light of JP 2007’s teachings that exemplified that the gel crosslinked hyaluronic acid successfully prevented tissue adhesions and in light of CN’295’s teachings that its gel disulfide bond cross-linked hyaluronic acid sulfhydryl derivative also prevented tissue adhesions. The success of both references composition in preventing tissue adhesions would also provide a reasonable expectation of success of this method.
It would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the gel disulfide bond cross-linked hyaluronic acid sulfhydryl derivative of CN ‘295 to apply 3% of a gel of disulfide crosslinked hyaluronic acid to tissue surrounding a site of a pelvic procedure in light of Liu’s teaching that 3% cross-linked thiolated hyaluronic acid is effective for preventing tissue adhesions.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over CN 102399295 (4/4/2012)(9/8/2021 IDS) in view of JP 2007/520589 (7/26/2007) and Liu et al. Biocompatibility and stability of disulfide-crosslinked hyaluronan films, Biomaterials Vol. 26, Issue 23, August 2005, pp 4737-4746 as applied to claims 15, 18 and 26-27 and further in view of Burns et al. Prevention of tissue injury and postsurgical adhesions by precoating tissues with hyaluronic acid solutions. J Surg Res. 1995; 59:644-52.
The teachings of CN ‘295 in view of JP 2007 and Liu are described supra. CN295 in view of JP 2007 and Liu do not expressly teach 4 mg/mL content of hyaluronic acid. This deficiency is made up for with the teachings of Burns et al.
Burns et al. (Burns) teaches the effectiveness of preventing surgical adhesions by coating tissues with low concentrations of hyaluronic acid. Burns teaches that the percentage of animals with no cecal adhesions from 11% to 50% in the 0.4% (4 mg/ml) hyaluronic acid treatment group. (See Abstract). Burns teaches that treating tissue with low concentration hyaluronic acid solutions limits formation of postsurgical adhesions. (See Abstract). 4 mg/ml is called for in instant claim 16 and is very close to 4.5 mg/ml called for in instant claim 17.
Given that CN teaches 5 mg/mL, 4.5 mg/mL is close enough that it would be expected to have the same properties as 5 mg/mL which is taught in CN. A person of ordinary skill in the art would likely expect that given that the amounts are so close, one skilled in the art would have expected them to have the same properties. Indeed, a prima facie case of obviousness usually exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.") See MPEP 2144.05
Additionally, CN ‘295 teaches that the amount of the disulfide crosslinked hyaluronic acid is a results-effective variable and it would be no more than routine experimentation to experiment to arrive at the amount of disulfide crosslinked hyaluronic acid in the gel called for in claim 17. A person of ordinary skill in the art would have been motivated to experiment with amounts that were close to 5 mg/mL in light of CN’s teaching that 5 mg/mL was effective for the prevention of tissue adhesions.
It would have been prima facie obvious for one of ordinary skill in the art following the CN ‘295 in view of JP 2007 and Liu method to apply 4% of a gel of disulfide crosslinked hyaluronic acid to tissue surrounding a site of a pelvic procedure in light of Burn’s teaching that 4% hyaluronic acid is effective for preventing tissue adhesions.
There would have been a reasonable expectation of success in using 4% of a gel of disulfide crosslinked hyaluronic acid to preventing tissue adhesions in light of CN ‘295’s teaching that using 5% gel of disulfide crosslinked hyaluronic acid successfully prevents adhesions.
Claims 19-20 and 28 under 35 U.S.C. 103 as being unpatentable over CN 102399295 (4/4/2012)(9/8/2021 IDS) in view of JP 2007/520589 (7/26/2007) and Liu et al. Biocompatibility and stability of disulfide-crosslinked hyaluronan films, Biomaterials Vol. 26, Issue 23, August 2005, pp 4737-4746 as applied to claims 15, 18 and 26-27 and further in view of CN 102070791 (5/25/2011).
The teachings of CN ‘295 in view of JP 2007 and Liu are described supra. CN ‘295 in view of JP 2007 and Liu do not expressly teach an amount of thiol groups. This deficiency is made up for with the teachings of CN ‘791.
CN ‘791 teaches a cross-linked hyaluronic acid/polyvinyl alcohol film that can function as a medicine carrier. (See Abstract). CN’ 791 teaches that the thiolated hyaluronic acid has a thiol group content of 10-500 µmol/g. (See [0013]). Thiol group content of 10-500 µmol/g overlaps with the from 10 to 100 µmol/g in claim 19 and the from 20 to 70 µmol/g in claim 20. Thiol group content of 10-500 µmol/g overlaps with the from 24 to 57 µmol/g in claim 28. CN ‘791 teaches that the thiolated hyaluronic acid are biodegradable and have good biological compatibility. (See [0016]).
It would have been prima facie obvious for one of ordinary skill in the art following the CN ‘295 in view of JP 2007 and Liu method of implanting a crosslinked disulfide hyaluronic acid gel in in a pelvis and to have the thiol content be 10-500 µmol/g in order to have a thiolated hyaluronic acid that is biodegradable and that has good biological compatibility as taught by CN ‘791.
Response to Arguments
Applicants’ arguments of December 10, 2025 and the December 10, 2025 Affidavit of Xiaozheng Shu have been fully considered and are not found to be persuasive.
Applicants note the new claim added and state that support can be found throughout the specification and claims as originally filed. It is noted that support for new claim 28 can be found at paragraph [0029] of the specification.
Applicants argue that the combination of CN ‘295 and JP 2007 does not teach or suggest a method according to claim 15. Neither reference teaches or suggests the use of a gel in which the content of disulfide crosslinked hyaluronic acid in the gel is from 3 to 4.5 mg/mL. Applicants note that the hyaluronic acid gel of JP 2007 as having been placed in a pelvis to prevent adhesion, is a hydrogel film and not disulfide crosslinked. Thus, a person of ordinary skill in the art would not have been motivated to use the gel of CN ‘295 in a method according to amended claim 15, particular wherein the content of disulfide crosslinked hyaluronic acid the gel is from 3 to 4.5 mg/mL.
Applicants argue and the Affidavit of Xiaozheng Shu attests that a person of skill in the art would not have expected that a low concentration (e.g. 3 to 4.5 mg/mL) disulfide crosslinked hyaluronic acid gel would be suitable to prevent adhesions after an abdominal operation in a method according to amended claim 15. As described in the instant application because the strength of the crosslinked hyaluronic gel is known to increase with concentration, a gel with higher disulfide crosslinked hylauronic acid content would be expected to physically isolate tissue and be better for preventing adhesion. Thus, Applicants argue and the Affidavit of Xiaozheng Shu attests that the common knowledge in the field taught away from the use of a gel with low crosslinked hyaluronic gel content according to the amended claims. See Yang et al, cited in the application on page 3.
However, contrary to this expectation, Applicants assert that a gel with a content of disulfide crosslinked hyaluronic acid from 3 to 4.5 mg/mL demonstrates unexpectedly improved properties over gels with a higher content of disulfide crosslinked hyaluronic acid, as seen in Examples 8 and 9. The applied references do not teach or suggest the use of a gel with a low content of disulfide crosslinked hyaluronic acid.
The obviousness arguments and the Affidavit of Xiaozheng Shu are not found to be sufficiently persuasive. The primary reason that the obviousness arguments are not found to be persuasive is that the newly applied prior art of Liu and Burns does teach the success of lower concentrations of hyaluronic acid in preventing surgical adhesions. Additionally, CN teaches the effectiveness of a gel formed from a solution having a concentration of 5 mg/ml and this is only 0.5 mg/mL away from the range of amounts that Applicants are claiming.(3 mg/mL to 4.5 mg/mL).
Specifically, Liu teaches a cross-linked hyaluronic acid that is a gel formed from a solution having a concentration of 3 mg/ml. (See [0015]). The 3 mg/ml content of the cross-linked hyaluronic acid falls within the from 3 to 4.5 mg/mL called for in instant claim 15 and is the actual 3 mg/mL called for in instant claim 27. Burns et al. (Burns) teaches the effectiveness of preventing surgical adhesions by coating tissues with low concentrations of hyaluronic acid. Burns teaches that the percentage of animals with no cecal adhesions from 11% to 50% in the 0.4% (4 mg/ml) hyaluronic acid treatment group. (See Abstract). Burns teaches that treating tissue with low concentration hyaluronic acid solutions limits formation of postsurgical adhesions. (See Abstract). 4 mg/ml is called for in instant claim 16 and is very close to 4.5 mg/ml called for in instant claim 17.
Given that CN teaches 5 mg/mL, the claimed amounts of 4.5 mg/mL are close enough that they would be expected to have the same properties as 5 mg/mL which is taught in CN. A person of ordinary skill in the art would likely expect that given that the amounts are so close, one skilled in the art would have expected them to have the same properties. Indeed, a prima facie case of obviousness usually exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.") See MPEP 2144.05
It would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the gel disulfide bond cross-linked hyaluronic acid sulfhydryl derivative of CN ‘295 to apply 3% of a gel of disulfide crosslinked hyaluronic acid to tissue surrounding a site of a pelvic procedure in light of Liu teaching that 3% cross-linked hyaluronic acid is effective for preventing surgical adhesions.
Respectfully, the assertion in the Affidavit that the prior art teaches away from the use of lower concentrations and does not provide a reason to believe that lower concentrations would perform as effectively as the higher concentration commonly used in the field is not found to be sufficiently persuasive because it is contradicted by some of the earliest prior art in the area. The earliest citations for using 4 mg/mL (0.4%) hyaluronic acid to prevent surgical adhesions are found in the mid 1990s. Research in this area established hyaluronic acid as an effective bioresorbable physical barrier. In 1995 Burns et al. evaluated 4 mg/mL in a rat cecal abrasion model, finding that it prevented tissue damage and significantly increased the percentage of animals with no adhesions from 11% to 50%. (See Burns Abstract).
Respectfully, the prior art suggests the use of low amounts of thiolated hyaluronic acid specifically for the successful prevention of adhesion following pelvic procedures. (See Liu et al. Biocompatibility and stability of disulfide-crosslinked hyaluronan films, Biomaterials Vol. 26, Issue 23, August 2005, pp 4737-4746.) Liu et al. teaches that as early as 2005, low concentrations of crosslinked thiolated hyaluronic acid specifically were being suggested for the successful prevention of adhesion following surgical pelvic procedures. (See page 4738 and the use of thiolated hyaluronic acid hydrogels successfully preventing post-surgical adhesion in a rat uterine horn model). Liu teaches a cross-linked thiolated hyaluronic acid that is a gel formed from a solution having a concentration of 3% w/v (3 mg/mL). (See page 4738 in Materials and Methods.) Liu teaches that the cross-linked thiolated HA hydrogel prevents post-surgical adhesion formation in a rat uterine horn model. (See page 4738). Liu teaches that thiolated hyaluronic acid films have surface smoothness which endows thiolated HA films with considerable potential as barriers to prevent the formation of post-operative adhesions. (See page 4742). Liu concluded that thiolated hyaluronic acid films have good biocompatibility and have considerable potential for clinical applications, including the prevention of post-operative surgical adhesions.
The CN reference teaches that 5 mg/mL is entirely effective to prevent tissue adhesion, Liu teaches that 3 mg/mL is effective to prevent tissue adhesion in pelvic procedures and Burns teaches as early as 1996 that 4% hyaluronic acid is effective to prevent tissue adhesion. A teaching away must be clear. See MPEP Sec. 2143 (VI). CN does not criticize, discredit or otherwise discourage the solution claimed. CN expressly teaches 5 mg/mL itself is effective, so there would appear to be a suggestion that at least an amount so close to an effective amount, as 4.5 mg/mL is, may also be successful.
Applicants’ assertion that a gel with a content of disulfide crosslinked hyaluronic acid from 3 to 4.5 mg/mL demonstrates unexpectedly improved properties over gels with a higher content of disulfide crosslinked hyaluronic acid is not found to be persuasive. The higher content of disulfide crosslinked hyaluronic acid that is in Applicants’ specification is 10 mg/mL. Example 9 in the instant specification states that in Figure 4, the disulfide crosslinked hyaluronic acid gels tested all had adhesion prevention effects, and the gels with contents of 3 mg/mL, 4 mg/mL, 4.5 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL and 8 mg/mL had a better adhesion prevention effect than the gel with a content of 10 mg/mL. However, CN teaches that gels with contents of 5 mg/mL are effective at adhesion prevention effect. Therefore, the prior art did teach that gels with contents of 3 mg/mL, 4 mg/ml and 5 mg/mL (amounts that Applicants are characterizing as lower amounts) are effective at adhesion prevention. Respectfully, an effect does not appear to be that unexpected when it is taught or suggested in the prior art.
Conclusion
No claims are allowed.
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SARAH CHICKOS
Examiner
Art Unit 1619
/SARAH ALAWADI/Primary Examiner, Art Unit 1619