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 .
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 15-20 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 claim 15 and claims dependent thereon, Claim 15 recites the limitation "The N,2,3,6-HS product according to Claims 1, wherein the 2O,3O,6O-HS product is a…". There is insufficient antecedent basis for “the 2O,3O,6O-HS product” in the claim. Claim 15 depends from claim 1 which only refers to a “N-, 2-O, 3-O, 6-O sulfated, heparan sulfate (N,2,3,6-HS) product”. Applicant appears to be using multiple terms to refer to the same product. Amending the claims to consistently refer to the N,2,3,5-HS product would provide clarity.
Claim 18 recites the limitation "the heparin product". There is insufficient antecedent basis for this limitation in the claim. Claim 18 depends from claim 1 which only refers to a “N-, 2-O, 3-O, 6-O sulfated, heparan sulfate (N,2,3,6-HS) product”. Applicant may have meant for this claim to depend from claim 16, as claim 17 has a parallel construction and claim 16 ultimately has antecedent basis for this term.
Regarding claim 18, The term “substantially free” in claim 18 is a relative term which renders the claim indefinite. The term “substantially free” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not know level what constitutes substantially free of the claimed impurities. Further depending on definition, the same composition may fall within or outside of the scope of the claims making it unclear what is being claimed.
Regarding claim 19 and claims dependent thereon, Claim 19 recites the limitation "within the heparin product". There is insufficient antecedent basis for this limitation in the claim. The term Heparin product has not been used prior to this instance. It is therefore unclear what applicant is referring to. If applicant intends that the H,2,3,6-HS product is heparin, making so through introduction of this would provide clarity. Alternatively referring to the H,2,3,6-HS product would provide clarity.
Regarding claim 20, The term “substantially free” in claim 20 is a relative term which renders the claim indefinite. The term “substantially free” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not know level what constitutes substantially free of the claimed impurities. Further depending on definition, the same composition may fall within or outside of the scope of the claims making it unclear what is being claimed.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
The claims recite a “N-, 2-O, 3-O, 6-O sulfated, heparan sulfate product formed by a process”, the recited process utilizes at least one engineered sulfotransferase enzyme, and an arylsulfate donor. A product by process is limited only to the structure implied by the steps, and not to the manipulations recited in the steps, See MPEP 2113, "The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) “. Thus the product claimed is a N,2,3,6 sulfated heparosan polysaccharide. As demonstrated in the instant specification and as evidenced by Chandrajoti (“De novo synthesis of a narrow size distribution low-molecular-weight heparin”, Glycobiology, 2014 Vol. 24, no. 5, 476-486) the action of 2-OST, 3-OST, 6-OST and c5-epimerase produce heparin structures (Figure 3 of Chandrajoti).
The natural products Heparan sulfate including Heparin fall within the scope of the instant claims. As noted throughout the instant specification these are natural products (in particular [0173]-[0174]). As evidenced by Nugent (“Heparin sequencing brings structure to the function of complex oligosaccharides”, PNAS, 2000, Vol. 97, no. 19, 10301-10303), the consensus sequence for the anticoagulant binding sequence of heparin is the claimed structure of claim 15 (Figure 2). This is further evidenced by Choay (“Structure-Activity Relationship in Heparin: A Synthetic Pentasaccharide with High affinity for Antithrombin III and eliciting high anti-factor Xa Activity, Biochemical and Biophysical Research Communications” , 1982, Vol 116, No. 2 492-499), (Figure 1), which more clearly shows the structure with sulfates present at 2,3 and 6 locations as well as the presence of N-acetylated glucosamines.
Claims 2-13 further describe the process by which the product is produced, but do not add any further structure. Claims 1-14 require the process to use at least one step using an aryl sulfate as a donor; however, as the substrate transfers the sulfate, this limitation does not differentiate or limit the product. Regarding claim 14, the presence of at least some acetylation on glucosamines has been shown in heparin by Choay and Nugent above. Regarding claim 15, the structure shown is the AT-III binding pentasacharide motif present in the natural product heparin as evidenced above by Choay and Nugent. Regarding claim 16 the anticoagulant activity of heparin is well established as noted in all three evidentiary references and the instant specification, further as evidenced by Chandrajoti unfractionated heparin has a molecular weight above the claimed level. Claims 17 and 18 further provide for the absence of some impurities; however, the structure of the heparan sulfates/heparin is not altered by purification and thus remain a product of nature.
This judicial exception is not integrated into a practical application because the claims are drawn to the product. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional structure or modification is present which alters the product to something that does not include within its scope products of nature.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by applicant’s admission, see MPEP 2129.
Regarding claim 1 and claims dependent there on, claim 1 recites a product by process , a product by process is limited only to the structure implied by the steps, and not to the manipulations recited in the steps, See MPEP 2113, "The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979)“. In the instant case that is the production of heparosan sulfate poly saccharide with further sulfate groups at the 2-O, 3-O and 6-O positions.
The instant specification states that the products made by the method of the application may have identical chemical structures to known products “[0168] The term, “substantially equivalent,” with respect to polysaccharides utilized as starting materials, formed as intermediates, acting as sulfo group acceptors, and/or synthesized as products according to any of the methods described herein, refers to one or more properties of a polysaccharide sample that are identical to those found in a polysaccharide sample characterized in the prior art. Such properties may include, but are not limited to, chemical structure, sulfation frequency and location, disaccharide unit composition, molecular weight profile, and/or anticoagulant activity. Even if the two polysaccharide samples have additional properties that may be different, such differences do not significantly affect their substantial equivalence. In a non-limiting example, anticoagulant N,2,3,6-HS products synthesized according to methods of the present invention can be substantially equivalent to the United States Pharmacopeia (USP) reference standard (CAS No: 9041-08-1) with respect to chemical structure, molecular weight profile, and/or anticoagulant activity, but can be produced at a different purity than the USP reference standard, which is isolated from natural sources and can contain non-trace amounts of other GAGs in the same sample.”
The specification then lists numerous products of the instant method that are substantially equivalent to known and available N,2,3,6-HS products including, heparin as noted above, multiple low molecular weight heparins, and various derivates ([0341]-[0354], [0365]-[0376]). These compounds have the structure and size claimed. Further these products can be obtained in purified form.
As they compounds are identical in chemical structure, they necessarily have the same properties. See MPEP 2112.01(II).
The instant claims are thus anticipated by the prior art disclosed by applicant.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11629364. Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of ‘364 outline the process by which the product of the instant claims is produced and will thus produce and render obvious the claimed products.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11542534. Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of ‘534 outline the process similar to the process that produces the instant product and will produce N,2,3,6-HS products which fall within the scope of the claimed products. The claims of ‘534 the render obvious the instant claims as they will produce products which fall within the scope of the instant claims.
Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11572550. Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of ‘550 recite a similar process with similar activities and recite the production of a N,2,3,6-HS product, further claiming the instantly claimed structure (claim 7), and further claims that it is equivalent to heparin, and further has the same size as claimed.
The claims of ‘550 thus render the instant claims obvious as they will produce products which fall within the scope of the instant claims.
Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11473068. Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of ‘068 recite a similar process with similar activities and recite the production of a N,2,3,6-HS product, further claiming the instantly claimed structure (claim 7), and further claims that it is equivalent to heparin, and further has the same size as claimed.
The claims of ‘068 thus render the instant claims obvious as they will produce products which fall within the scope of the instant claims.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 7-9 of U.S. Patent No. 11708567. Although the claims at issue are not identical, they are not patentably distinct from each other because the method of ‘567 can included 933 may be include sulfate groups at the 2-O and 3-O position and thus ‘567 and the instant claims include products which fall within the scope of each other.
Claim 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 21-25 of copending Application No. 18096933 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the method and product of ‘933 may be include sulfate groups at the 2-O and 3-O position and thus ‘933 and the instant claims include products which fall within the scope of each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/CHARLES Z CONSTANTINE/Examiner, Art Unit 1657
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657