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 application is a divisional application of US application 14/469028, currently pending, filed August 26, 2026, which claims benefit of provisional application 61/871352, filed August 29, 2013. Claims 1-13 are pending in this application and examined on the merits herein.
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.
Claims 1-13 are 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.
Base claim 1 is directed to a method for treating inflammation with a therapeutic agent that is described as a conjugate of a glycosaminoglycan and an active compound. However, claim 1 further contains a limitation that the active compound “consists of anti-inflammatory drug, anti-allergy drug, and steroid.” It is unclear how this listing is meant to modify the term “active compound.” For example, it could mean that the single active compound is selected from one of the three classes of drugs recited in the claim. Alternately, it could require three different active agents, one selected from each of the three types of compounds described. Finally, it could require that the active agent be a single compound having all three of the listed activities. Therefore independent claim 1 and dependent claims 2-13 are indefinite. A similar issue also arises in claim 5, which refers to a steroid and requires that the steroid is both budesonide and prednisolone, which could be interpreted as referring to a single steroid that is either budesonide or prednisolone, or a mixture of both of these steroids.
For the sake of the present action, the claims will be interpreted as if the aforementioned listings required only one of the listed options. (i.e. the active compound is selected from a group consisting of an anti-inflammatory drug, an anti-allergy drug, and a steroid)
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 11 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 11 depends form claim 1 which is directed to a method for treating inflammation. However claim 11 has as its sole additional limitation the requirement that the inflammation is either acute or chronic. Since a condition such as inflammation must by necessity be either acute or chronic, listing both alternatives in claim 11 therefore fails to further limit 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 6, and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bilkova et al. (Reference included with PTO-1449)
Independent claim 1 is directed to a process comprising administering to a subject in need thereof a conjugate of a glycosaminoglycan and an active compound, which can include a steroid. Dependent claims 6, 9, and 10 further describe the structural characteristics of the glycosaminoglycan and the covalent linkage.
Bilkova et al. discloses that prednisolone and methylprednisolone are anti-inflammatory agents used to treat a wide variety of conditions including inflammatory and autoimmune conditions, which suffer from systemic side effects. (p. 3577 left column first paragraph) Bilkova et al. further discloses the use of conjugates, including polymeric conjugates, to overcome these problems. (p. 3577 left column last paragraph) One of the specific conjugates described is a direct ester conjugate of methylprednisolone to hyaluronic acid, which is a steroid conjugate according to claim 1 and meets the limitations of dependent claims 6 and 9. (p. 3587 right column last paragraph, p. 3588 scheme 17) Regarding claim 10, this conjugate is described as using a HA having a molecular weight of 500-750 kDa. Regarding claim 11, any condition must be either acute or chronic.
Therefore Bilkova et al. anticipates the present claims.
Claims 1, 2, 7, and 9-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Foreign publication EP2497785A2 to Sekigaku Corporation. (Reference included with PTO-1449, herein referred to as Sekigaku)
Independent claim 1 is directed to a process comprising administering to a subject in need thereof a conjugate of a glycosaminoglycan and an active compound, which can include a steroid. Dependent claims 2, 7, 9, and 10 further describe the structural characteristics of the anti-inflammatory drug, glycosaminoglycan and the covalent linkage.
Sekigaku discloses hyaluronic acid derivatives introduced with NSAIDs which can be used to treat pain and inflammation in arthritis. (p. 3 paragraph 10) Such a method of administering a HA attached to an anti-inflammatory agent would necessarily anticipate claims 1, 9, and 11. Regarding claim 2, Sekigaku discloses conjugates comprising the anti-inflammatory agent diclofenac which is also a COX-2 inhibitor. (p. 38 paragraph 237 p. 39 paragraph 238) Regarding claim 7, Sekigaku discloses a conjugate of HA and the anti-inflammatory agent having a covalent spacer linked to the carboxylate by an amide bond. (p. 3 paragraph 12) Regarding claim 10, Sekigaku disclose a HA-aminopropanol-diclofenac conjugate wherein the HA has a molecular weight of 65 kDa. (p. 31 paragraphs 173-174) Regarding claims 12 and 13, Sekigaku discloses a method of treating rheumatoid arthritis. (p. 14 paragraph 90)
For these reasons Sekigaku anticipates the present claims.
Claims 1, 2, 5, and 7-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Miyamoto et al. (US pre-grant publication 2009/0118348, cited in PTO-892)
Independent claim 1 is directed to a process comprising administering to a subject in need thereof a conjugate of a glycosaminoglycan and an active compound, which can include a steroid. Dependent claims 2, 7, and 9 further describe the structural characteristics of the glycosaminoglycan and the covalent linkage.
Miyamoto et al. discloses a conjugate of a drug with a photocrosslinked hyaluronic acid. (p. 1 paragraph 12) In a specific embodiment the drug is bound to the HA through a spacer having two or more functional groups, such as amine and carboxylate, and can preferably be bound through an amide bond to the carboxyl of the hyaluronic acid. (p. 2 left column, e.g. elements 2 and 9) These conjugates can specifically be administered locally, for example to treat chronic inflammatory disease such as rheumatoid arthritis, wherein the active agent id for example a non-steroidal anti-inflammatory drug. (p. 3 paragraph 15) The linkers can include for example amino acids or peptides as recited in claim 8. (p. 4 paragraph 29) Drugs that can be administered in this manner include for example nonsteroidal anti-inflammatory drugs, antihistamines, and steroids including prednisolone. (p. 5 paragraph 33) Regarding claim 10, Miyamoto discloses a preferred range of 600-1500 kDa for the molecular weight of the HA. (p. 3 paragraph 22) Therefore Miyamoto anticipates the present claims.
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, 5, 6, and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Bilkova et al. (Reference included with PTO-1449)
The disclosure of Bilkova et al. is discussed above. While it is concluded that the disclosure of Bilkova et al. anticipates the present claims, even assuming for the sake of argument that the disclosure of Bilkova does not literally anticipate a method comprising administering the disclosed methylprednisolone-HA ester to a subject suffering from an inflammatory, allergic, or autoimmune disease, it would have been obvious to one of ordinary skill in the art at the time of the invention to administer this conjugate to this patient population, in view of the discussion by Bilkova (p. 3587 section 3.3) of these specific conjugates describing them as having been developed for the purpose of treating inflammatory and/or degenerative arthropathies such as rheumatoid arthritis, by intraarticular injection. This disclosure would specifically have motivated one of ordinary skill in the art to administer this conjugate by intraarticular injection to a patient suffering from rheumatoid arthritis, thereby infringing the claimed invention.
Furthermore regarding claim 5, while the conjugates described by Bilkova specifically include methylprednisolone as the steroid, Bilkova et al. discloses polysaccharide conjugates of prednisolone (p. 3586 scheme 14) and describes both prednisolone and methylprednisolone as anti-inflammatory glucocorticoids. (p. 3577 left column first paragraph) Therefore one of ordinary skill in the art at the time of the invention would have seen these two compounds as equivalents usable for the same purpose, and found it to be obvious to use prednisolone in a HA conjugate in place of methylprednisolone.
Regarding claims 12 and 13, the reference to inflammatory arthropathy on p. 3598 section 3.3, combined with the reference to rheumatoid arthritis (p. 3577 left column first paragraph) would have suggested to one of ordinary skill in the art to use the disclosed steroid-HA conjugate specifically for the purpose of treating this particular disease.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Sekigaku as applied to claims 1, 2, 7, and 9-13 above, and further in view of McCormack. (Reference included with PTO-892)
The disclosure of Sekigaku is discussed above. Sekigaku does not disclose an embodiment wherein the COX-2 inhibitor is celecoxib. However, McCormack discloses that celecoxib is a selective COX-2 inhibitor. (p. 2458 first paragraph) Celecoxib is further disclosed to be effective for treating rheumatoid arthritis. (pp. 2467-2469 section 3.2)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use celecoxib as the anti-inflammatory agent in the conjugates described by Sekigaku. Specifically, the disclosure of McCormack would lead one of ordinary skill in the art to see diclofenac and celecoxib as equivalents usable for the same purpose of treating rheumatoid arthritis.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Sekigaku as applied to claims 1, 2, 7, and 9-13 above, and further in view of Prestwich et al. (US patent 5874417, cited in PTO-1449)
The disclosure of Sekigaku et al. is discussed above. Sekigaku does not disclose a conjugate wherein the linker is adipic dihydrazide. However, Prestwich discloses that conjugation of hyaluronic acid is known in the art to be useful for drug delivery but is complicated by the fact that the chemical treatments necessary to produce the conjugates leads to alterations in the physical and chemical characteristics of the hyaluronic acid. (column 1 lines 43-67) Prestwich et al. further discloses hyaluronic acid functionalized with a dihydrazide which can be further coupled to biologically active materials. (column 3 lines 29-35, 55-61) These conjugates can be produced under mild conditions that do not disrupt the integrity of the HA. (column 3 line 62 – column 4 line 16) Adipic dihydrazide is disclosed as one of the useful embodiments of a dihydrazide linker. (column 8 lines 46-55) Drugs that can be conjugated in this manner include carboxylate-containing anti-inflammatory agents and steroids. (column 13 lines 25-50)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use adipic dihydrazide as the linker in the conjugates described by Sekigaku. One of ordinary skill in the art would have seen the disclosure of Prestwich as suggesting that the use of adipic dihydrazide would represent an improvement over the aminopropanol linker described by Sekigaku, as it could be introduced under mild conditions that would be less disruptive to the integrity of the hyaluronic acid.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Bilkova as applied to claims 1, 5, 6, and 9-13 above, and further in view of Prestwich et al. (US patent 5874417, cited in PTO-1449)
The disclosure of Bilkova et al. is discussed above. Bilkova does not disclose a conjugate wherein the steroid is attached to the HA by an adipic dihydrazide linker. However, Bilkova does disclose the use of linkers to attach steroids to other polymers elsewhere in the reference. (p. 3584 scheme 11, p. 3586 scheme 14, p. 3588 scheme 16, p. 3589 scheme 18)
Prestwich discloses that conjugation of hyaluronic acid is known in the art to be useful for drug delivery but is complicated by the fact that the chemical treatments necessary to produce the conjugates leads to alterations in the physical and chemical characteristics of the hyaluronic acid. (column 1 lines 43-67) Prestwich et al. further discloses hyaluronic acid functionalized with a dihydrazide which can be further coupled to biologically active materials. (column 3 lines 29-35, 55-61) These conjugates can be produced under mild conditions that do not disrupt the integrity of the HA. (column 3 line 62 – column 4 line 16) Adipic dihydrazide is disclosed as one of the useful embodiments of a dihydrazide linker. (column 8 lines 46-55) Drugs that can be conjugated in this manner include carboxylate-containing anti-inflammatory agents and steroids. (column 13 lines 25-50)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use adipic dihydrazide as the linker in the conjugates described by Bilkova. One of ordinary skill in the art would have seen the disclosure of Prestwich as suggesting that the use of adipic dihydrazide would represent an improvement over the other linkers described by Bilkova, as it could be introduced under mild conditions that would be less disruptive to the integrity of the hyaluronic acid.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Miyamoto et al. as applied to claims 1, 2, 5, and 7-13 above, and further in view of Kozlowski et al. (US pre-grant publication 2011/0171716, cited in PTO-892)
The disclosure of Miyamoto et al. is discussed above. Miyamoto et al. does not specifically disclose an embodiment wherein the antihistamine is fexofenadine. However, Kozlowski et al. discloses a different mechanism for derivatizing a water-soluble polymer in order to conjugate a drug moiety as a drug delivery vehicle. (p. 1 paragraph 8 – p. 2 paragraph 32) Agents that can be administered in this manner include the antihistamine fexofenadine. (p. 14 paragraph 203)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use fexofenadine as the antihistamine agent in the conjugates disclosed by Miyamoto. One of ordinary skill in the art would have found this to be obvious based on the fact that Kozlowski discloses that this antihistamine can be covalently attached to a drug delivery polymer, and furthermore because Miyamoto discloses conjugation of antihistamines generally to HA.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Miyamoto et al. as applied to claims 1, 2, 5, and 7-13 above, and further in view of McCormack. (Reference included with PTO-892)
The disclosure of Miyamoto et al. is discussed above. Miyamoto et al. does not specifically disclose an embodiment wherein the anti-inflammatory agent is celecoxib. However, McCormack discloses that celecoxib is a selective COX-2 inhibitor. (p. 2458 first paragraph) Celecoxib is further disclosed to be effective for treating rheumatoid arthritis. (pp. 2467-2469 section 3.2)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use celecoxib as the anti-inflammatory agent in the conjugates described by Miyamoto. Specifically, the disclosure of McCormack would lead one of ordinary skill in the art to see diclofenac and celecoxib as equivalents usable for the same purpose of treating rheumatoid arthritis.
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, 2, 6, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 11643431. (Cited in PTO-892, herein referred to as ‘431) Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘431 claims a method for treating pulmonary inflammation comprising administering to a subject in need thereof a conjugate of hyaluronic acid with at least one molecular of the anti-inflammatory COX-2 inhibitor nimesulide attached to a HA carboxylate by an amide linkage. Administering this conjugate therefore anticipates present claims 1, 2, 6, and 9. Regarding claim 10, claim 3 of ‘431 recites a molecular weight range of 10-2000 kDa, falling within the 5-200 kDa range recited by present claim 10. Regarding present claims 11 and 12, claim 1 of 431 specifically recited an embodiment wherein the inflammation is from acute lung injury, falling within the scope of these claims.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 10/2/2026
