Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Detailed Action
This application is a divisional application of US application 16/625342, now US patent 11993627, filed December 20, 2019, which is a national stage application of PCT/US2018/040774, filed July 3, 2018, which claims benefit of provisional application 62/528243, filed July 3, 2017. Claims 1-13 are pending in this application and examined on the merits herein. Applicant’s preliminary amendment submitted August 14, 2024, is acknowledged wherein claims 3-13 are amended and claims 14-22 are canceled.
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 12 and 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.
Regarding claims 12 and 13, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Additionally, claim 12 includes the chemical abbreviation NHFTA, which is not clearly defined in the claim or specification. This is likely a typographical error and was intended to be NHTFA, which refers to trifluoroacetamide.
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 12 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 12 depends from claim 1, which describes a method of making a synthetic chondroitin sulfate oligosaccharide This oligosaccharide must by necessity be sulfated. However, claim 12 defines the oligosaccharide in terms of one of a number of structures. In particular, the pentasaccharide structure includes embodiments wherein R1=R2=H, which are not sulfated. Therefore claim 12 fails to include all the limitations of 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, 3, 4, 8, 9, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sugiura et al. (Reference included with PTO-892)
Independent claim 1 is directed to a method of synthesizing a chondroitin sulfate comprising providing a chondroitin backbone, performing elongation steps using KfoC, and/or sulfation using chondroitin sulfate sulfotransferases and PAPS to produce a synthetic chondroitin sulfate oligosaccharide. Dependent claims 3 and 4 require three or four different enzymatic steps. Claims 5, 8, and 9 define the CS oligosaccharide as homogeneous, structurally defined, and unnatural. Claims 6 and 7 specify the length of the oligosaccharide.
Sugiura et al. discloses a library of chondroitin sulfate oligosaccharides having specifically defined length and sulfation patterns, for the study of the molecular interactions of CS. (p. 43391 left column last paragraph – right column first paragraph) The library was constructed by the polymerization of glucuronic acid and N-acetylgalactosamine saccharides onto a chondroitin backbone using the enzyme K4CP, which is the chondroitin polymerase from E. coli K4. (p. 43392 left column last paragraph, see also abbreviations at the bottom of p. 43390, establishing that K4CP is an abbreviation for the same E. coli K4 polymerase recited in the present claims) The backbone was then sulfated using Chondroitin-4-sulfotransferase and chondroitin-6-sulfotransferase enzymes and the sulfate donor PAPS, to form the final oligosaccharides. (p. 43392 right column first paragraph) performing this synthesis using all of these enzymatic steps (see also figure 1 on p. 43394) would anticipate the process of present claims 1 and 3-5. Furthermore because the structures are described as chemically defined the process would anticipate present claim 9. Regarding claim 11, CSA, CSC, CSD, and CSE are all synthesized. (p. 43393 table 1) According to figure 1a on p. 43394, unnatural trisulfated CS is also synthesized.
For these reasons Sugiura et al. 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 5-7, 10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sugiura et al. (Reference included with PTO-892) as applied to claims 1, 3, 4, 8, 9, and 11, further in view of Belot et al. (Reference included with PTO-892)
The disclosure of Sugiura et al. is discussed above. Sugiura et al. does not specifically disclose a method of making a substantially homogeneous oligosaccharide or an oligosaccharide having the specific length recited in present claims 6-7, or the specific structure recited in present claim 12.
Belot et al. discloses that there is a need to make precisely chemically defined chondroitin sulfate oligosaccharides for the study of the various biological activities of these molecules. (p. 88 right column first paragraph) Specific oligosaccharides synthesized include 4-O- and 6-O- sulfated oligosaccharides. (p. 89 figure 1) The 6-O-slufated product would furthermore infringe the embodiment of claim 12 wherein R1=sulfate, R2=H, and R3=NHAc, and a process of producing it by making the backbone and then adding sulfates with a sulfotransferase would infringe the embodiment wherein R1=R2=H and R3=NHAc.
It would have been obvious to one of ordinary skill in the art at the time of the invention to use chemoenzymatic synthesis as described by Sugiura et al. to produce a homogeneous sample of the specific oligosaccharide recited by Belot. One of ordinary skill in the art would have seen the disclosure of Belot as describing a need to make oligosaccharides such as pentasaccharides for the study of the biological activities of chondroitin sulfate, and furthermore would have seen Sugiura as providing a method for reliably making chemically defined oligosaccharides which would be reasonably expected to be useful for making such oligosaccharides.
Regarding claim 10, while the cited references do not specifically describe making a particular amount of oligosaccharide, it would have been obvious to one of ordinary skill in the art at the time of the invention to make any arbitrarily large amount of the pentasaccharide described by Belit et al. One of ordinary skill in the art would have seen the disclosure of Belot as indicating that these oligosaccharides are useful for studying the biological activities of CS and would have been motivated to make as much as is necessary to carry out any relevant experiments for which they are required.
Therefore the invention taken as a whole is prima facie obvious.
Claims 5-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Sugiura et al. (Reference included with PTO-892) as applied to claims 1, 3, 4, 8, 9, and 11, further in view of Matsumoto et al. (Reference included with PTO-892)
The disclosure of Sugiura et al. is discussed above. Sugiura et al. does not specifically disclose a method of making a substantially homogeneous oligosaccharide or an oligosaccharide having the specific length recited in present claims 6-7.
However, Matsumoto et al. discloses a chemically synthesized hexasaccharide fragment of chondroitin sulfate E. (p. 755 left column second and third paragraphs, also figure 1) This hexasaccharide was also administered to an animal model of rheumatoid arthritis. (p. 544 sections 2.4-2.7) The hexasaccharide was seen to inhibit the severity of RA in treated mice. (p. 758 left column first paragraph)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use chemoenzymatic synthesis as described by Sugiura et al. to produce a homogeneous sample of the specific oligosaccharide recited by Matsumoto et al. One of ordinary skill in the art would have seen the disclosure of Matsumoto as describing a need to make oligosaccharides such as the disclosed hexasaccharide as a therapeutic agent for rheumatoid arthritis, and furthermore would have seen Sugiura as providing a method for reliably making chemically defined oligosaccharides which would be reasonably expected to be useful for making such oligosaccharides.
Regarding claim 10, while the cited references do not specifically describe making a particular amount of oligosaccharide, it would have been obvious to one of ordinary skill in the art at the time of the invention to make any arbitrarily large amount of the oligosaccharide described by Matsumoto et al. One of ordinary skill in the art would have seen the disclosure of Matsumoto as indicating that these oligosaccharides are useful for studying the biological activities of CS and would have been motivated to make as much as is necessary to carry out any relevant experiments for which they are required.
Therefore 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 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 11633424 (Cited in PTO-892, herein referred to as ‘424) in view of Sugiura et al. (Reference included with PTO-892).
Claim 1 of ‘424 claims a method of treating histone toxicity in a subject comprising administering to the subject a chondroitin sulfate having a specifically defined backbone, length, and sulfation pattern, being a 19-mer or 13-mer. Dependent claim 4 further defines the oligosaccharide as having the same structure as recited in present claim 13.
The claims of ‘424 do not claim a method of making said oligosaccharides comprising the same steps recited in present claims 1 and 3-4. However, as discussed previously under 35 USC 102 and 103, Sugiura et al. does disclose such a process for making CS oligosaccharides.
It would have been obvious to one of ordinary skill in the art at the time of the invention to use chemoenzymatic synthesis as described by Sugiura et al. to produce a homogeneous sample of one of the specific therapeutic CS oligosaccharides used in the method claimed by ‘424. One of ordinary skill in the art would have seen the claimed method of ‘424 as providing a need to make the disclosed oligosaccharides as a therapeutic agent for histone toxicity, and furthermore would have seen Sugiura as providing a method for reliably making chemically defined oligosaccharides which would be reasonably expected to be useful for making such oligosaccharides.
Regarding claim 10, while the cited references do not specifically describe making a particular amount of oligosaccharide, it would have been obvious to one of ordinary skill in the art at the time of the invention to make any arbitrarily large amount of the oligosaccharide used in the claimed method of ‘424. One of ordinary skill in the art would have seen the claims of ‘424 as indicating that these oligosaccharides are useful for studying the biological activities of CS and would have been motivated to make as much as is necessary to carry out any relevant experiments for which they are required.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
Claims 1 and 3-13 are rejected. Claim 2 is objected to for depending from a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claim and any intervening claims.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 9/1/2026
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