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 .
Detailed Action
This office action is a response to applicant’s communication submitted June 26, 2026, wherein claim 1 is amended and claims 2 and 6 are canceled. This application is a national stage application of PCT/IB2022/054315, filed May 10, 2022, which claims benefit of foreign application IT102021000012737, filed May 18, 2021.
Claims 1, 3-5, and 7-18 are pending in this application.
Claims 1, 3-5, and 7-18 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted June 26, 2026, with respect to the rejection of claims 1, 2, 6, and 14-16 under 35 USC 102(a)(1) for being anticipated by Liang et al., has been fully considered and found to be persuasive to remove the rejection as Liang et al. has been amended so as to no longer include embodiments wherein the anionic polysaccharide is carrageenan. Therefore the rejection is withdrawn.
The following rejections of record in the previous action are maintained:
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, 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.
Claims 1, 3-5, 7-11, and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al. (Reference of record in previous action) in view of Luyten et al. (Reference of record in previous action) in view of Hashimoto et al. (US pre-grant publication 2013/0203697, of record in previous action)
Independent claim 1 is directed to a composition of a crosslinked polyanionic polysaccharide, comprising a crosslinked polyanionic polysaccharide crosslinked by direct ester bonds or by one of several classes or spacer moieties, and a polyamine saccharide, which is either a chitosan or a functionalized chitosan having at least 20% N-substitution with glycosides.
Dependent claims 3 and 4 further define the polyanionic polysaccharide more narrowly, for example as hyaluronic acid. Dependent claims 7-10 further describe the functionalized chitosan.
Tan et al. discloses biomaterials for use in a cell scaffold for the support of chondrocytes in cartilage repair. (p. 15 left column first paragraph – right column second paragraph) One of the materials tested is chitosan-g-lactose, which is chitosan amino-modified with lactose, resulting in about 66% N-modification. (p. 16 right column first and second paragraph) This material falls within the scope of present claims 7-10. Furthermore the chitosan used has a Mn of 6.2x105, or 620 kDa, which falls within the scope of present claim 11. (p. 16 left column last paragraph) This material was then prepared in a film either alone or in a blend with the polyanionic polysaccharide heparin. (p. 16 left column last paragraph) Tan et al. does not disclose an embodiment wherein the chitosan-g-lactose is blended with a crosslinked anionic polysaccharide.
Luyten et al. discloses the use of autologous chondrocyte implantation in the treatment of osteoarthritis. (p. 292 left column first paragraph – p. 293 right column third paragraph) Therefore one of ordinary skill in the art would have considered the cell scaffolds described by Tan et al. to be useful particularly for autologous chondrocyte transplantation for the treatment of osteoarthritis.
Hashimoto et al. discloses self-crosslinked hyaluronic acid. (p. 1 paragraphs 6-7) Then applied in an injection, this material is capable of providing a curative effect on knee osteoarthritis, even when administered infrequently, as proposed to the result obtained for non-crosslinked HA. (p. 1 paragraph 9) The crosslinked HA is crosslinked by direct esterification, and therefore falls within the scope of crosslinked polyanionic polysaccharides recited in present claims 1-4. (p. 1 paragraph 10) Furthermore it has a molecular weight of about 800 kDa, falling within the scope of claim 5. (p. 1 paragraph 12)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use the chitosan-g-lactose as a scaffold for autologous chondrocyte transplantation specifically for the treatment of osteoarthritis, as recited in claims 17 and 18. One of ordinary skill in the art would have found this to be obvious based on the fact that Tan discloses it is capable of supporting chondrocytes, and Luyten et al. discloses that such chondrocyte scaffolds are useful for treating osteoarthritis. Furthermore it would also have been obvious to administer this material in combination with the crosslinked HA described by Hashimoto et al., in view of the fact that both materials are described as useful for treating the same condition, namely osteoarthritis, and are both administered by injection.
Regarding claim 13, as heparin is further disclosed as a useful component of the compositions of Tan, it would also have been obvious to one of ordinary skill in the art at the time of the invention to include heparin as a further biological substance. Regarding claims 14-15, examples 4 and 5 on pp. 9-10 of Hashimoto suggest preparing aqueous injectable compositions having a pH of 7.0.
Claims 1, 3-5 and 7-18 are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al. (Reference of record in previous action) in view of Luyten et al. (Reference of record in previous action) in view of Leshchiner et al. (US pre-grant publication 2007/0036745, of record in previous action)
Independent claim 1 is directed to a composition of a crosslinked polyanionic polysaccharide, comprising a crosslinked polyanionic polysaccharide crosslinked by direct ester bonds or by one of several classes or spacer moieties, and a polyamine saccharide, which is either a chitosan or a functionalized chitosan having at least 20% N-substitution with glycosides.
Dependent claims 3 and 4 further define the polyanionic polysaccharide more narrowly, for example as hyaluronic acid. Dependent claims 7-10 further describe the functionalized chitosan.
Tan et al. discloses biomaterials for use in a cell scaffold for the support of chondrocytes in cartilage repair. (p. 15 left column first paragraph – right column second paragraph) One of the materials tested is chitosan-g-lactose, which is chitosan amino-modified with lactose, resulting in about 66% N-modification. (p. 16 right column first and second paragraph) This material falls within the scope of present claims 7-10. Furthermore the chitosan used has a Mn of 6.2x105, or 620 kDa, which falls within the scope of present claim 11. (p. 16 left column last paragraph) This material was then prepared in a film either alone or in a blend with the polyanionic polysaccharide heparin. (p. 16 left column last paragraph) Tan et al. does not disclose an embodiment wherein the chitosan-g-lactose is blended with a crosslinked anionic polysaccharide.
Luyten et al. discloses the use of autologous chondrocyte implantation in the treatment of osteoarthritis. (p. 292 left column first paragraph – p. 293 right column third paragraph) Therefore one of ordinary skill in the art would have considered the cell scaffolds described by Tan et al. to be useful particularly for autologous chondrocyte transplantation for the treatment of osteoarthritis.
Leshchiner et al. discloses gels of divinylsuflone (DVS) crosslinked hyaluronic acid. (p. 1 paragraph 4) In particular, Leshchiner discloses injecting these gels for viscosupplementation and treatment of osteoarthritis. (p. 2 paragraphs 10-13) In a preferred embodiment the HA has a molecular weight of 300-400 kDa. (p. 6 paragraph 54) These hyaluronic acids therefore fall within the scope of crosslinked polyanionic polysaccharides as recited in present claims 1 and 3-5.
It would have been obvious to one of ordinary skill in the art at the time of the invention to use the chitosan-g-lactose as a scaffold for autologous chondrocyte transplantation specifically for the treatment of osteoarthritis, as recited in claims 17 and 18. One of ordinary skill in the art would have found this to be obvious based on the fact that Tan discloses it is capable of supporting chondrocytes, and Luyten et al. discloses that such chondrocyte scaffolds are useful for treating osteoarthritis. Furthermore it would also have been obvious to administer this material in combination with the crosslinked HA described by Leshchiner et al., in view of the fact that both materials are described as useful for treating the same condition, namely osteoarthritis, and are both administered by injection.
Regarding claim 13, as heparin is further disclosed as a useful component of the compositions of Tan, it would also have been obvious to one of ordinary skill in the art at the time of the invention to include heparin as a further biological substance. Regarding claim 15-16, these claims are infringed by an aqueous material for intraarticular injection as described by Luyten. Regarding claim 14, p. 4 paragraph 31 and p. 7 paragraph 70 describe that while the composition can be washed with acidic saline, it can then be further washed to physiological pH if necessary.
Still further, regarding claim 12, as discussed previously, Leshchiner et al. discloses providing a hyaluronic acid and carrying out crosslinking with DVS as recited in steps (i) and (ii) of claim 12. Regarding step (iii) the washing step to physiological pH would meet the limitations of this step. Regarding step (iv) of claim 12, combining this composition with the chitosan-g-lactose described by Tan would meet the limitations of this step. Regarding step (v), this step is vague as to the amount of time that the composition is left at room temperature and what if any further modification of the composition occurs as a result of this step. Therefore any time at which the composition is at room temperature would infringe this step, for example preparing it for injection.
For these reasons the invention taken as a whole is prima facie obvious.
Double Patenting
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.
Claims 1, 3-5, 7-11, and 13-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 9, 10, and 13-15 of U.S. Patent No. 11116787 (of record in previous action, herein referred to as ‘787) in view of Hashimoto et al. (US pre-grant publication 2013/0203697, of record in previous action)
Claim 15 of ‘787 is directed to a composition such as an aqueous solution comprising N-lactose chitosan having a degree of lactose substitution of at least 40% and a mw of 200-400 kDa, and a hyaluronic acid having a MW of 1000-1600 kDa. This composition differs from the composition recited in present claims 1-5, 7-11, 15, and 16 only in that the hyaluronic acid is not crosslinked. Claims 1, 8-10, and 13-14 of ‘787 However, these compositions can be used for tissue repair through proliferation of chondrocytes including cartilage and osteoarthritis in claims 13-14. As discussed above under 35 USC 103, Hashimoto et al. discloses that crosslinking improves the properties of hyaluronic acid used for cartilage repair. Therefore one of ordinary skill in the art would have seen Hashimoto et al. as suggesting using crosslinked HA in the compositions recited in the claims of ‘787 in the expectation that their utility for the intended purpose would be improved.
Response to Arguments
Applicant’s arguments, submitted June 26, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. With respect to all rejections still pending, Applicant argues that the incorporation of the limitations of claim 6 into claim 1 renders claim 1 nonobvious. However, as presently written claim 1 describes, in the alternative, either a carboxylated polysaccharide or a sulfated polysaccharide. The incorporated limitations from claim 6 only apply to embodiments wherein the polysaccharide is a sulfated polysaccharide, but not to embodiments wherein it is a carboxylated polysaccharide. Therefore this argument is not persuasive with respect to any of the above rejections, which are based on the embodiment wherein the polyanionic polysaccharide is hyaluronate.
With respect to the rejections under 35 USC 103 (Tan in view of Luyten in view of Hashimoto or Tan in view of Luyten in view of Leshchiner) Applicant further argues that the chitosans disclosed by Tan are crosslinked to heparin and therefore do not fall within the scope of the compositions of claim 1. However, the basis for the rejection is not that the “chitosan-g-heparin” composition described by Tan infringes the claims. Rather the rejection is based on the argument that it would have been obvious to use Tan’s chitosan-g-lactose material as a scaffold for cultured chondrocytes for treating osteoarthritis, and additionally include crosslinked hyaluronic acid in the composition, based on the known benefit of crosslinked HA for treating osteoarthritis, as described by Hashimoto or Leshchiner. It is also noted that based on the disclosure of Tan, the non-cross-linked chitosan-g-lactose is seen to be superior to chitosan-g-heparin in terms of cell attachment, viability, and proliferation. (see p. 19 figure 4, p. 21 figures 8 and 9) Therefore it would be reasonable for one of ordinary skill in the art to prefer chitosan-g-lactose to chitosan-g-heparin when producing a cell culture for therapeutic use.
For these reasons the rejections are deemed proper and maintained.
Conclusion
No claims are allowed in this action. THIS ACTION IS MADE FINAL. 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 ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 8/19/2026
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