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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 25, 2026 has been entered.
DETAILED ACTION
3. Claims 12 and 15 – 22 are pending in this application and are examined on the merits herein. Applicant’s Amendment and Remarks, filed March 25, 2026, is entered, wherein claim 12 is amended and claims 1 – 11 and 13 – 14 are canceled.
Priority
This application is a national stage application of PCT/EP2021/068202, filed July 1, 2021, which claims benefit of foreign priority document EP20183661.6, filed July 2, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Rejections
5. The rejection of claims 12 and 15 – 20 in the previous Office Action, mailed December 30, 2025, under 35 U.S.C. 103 as being unpatentable over Senni et al. in view of Colliec-Jouault et al. and Batzios et al. with evidence provided by Martins et al. has been considered and is withdrawn in view of amended claim 12.
The rejection of claims 21 – 22 in the previous Office Action, mailed December 30, 2025, under 35 U.S.C. 103 as being unpatentable over Senni et al. in view of Colliec-Jouault et al. and Batzios et al. with evidence provided by Martins et al. as applied to claims 12 and 15 – 20 above, and further in view of National MPS Society has been considered and is withdrawn in view of amended claim 12.
The rejection of claims 12, 15, and 17 – 19 in the previous Office Action, mailed December 30, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7 of U.S. Patent No. 11219638B2 in view of Senni et al. and Batzios et al. with evidence provided by Martins et al. has been considered and is withdrawn in view of the amended claim 12.
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.
Claim 17 is 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.
a. Regarding claim 17, the phrase "in particular" renders the claim indefinite because it functions as exemplary language in the present claim and it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 15 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 requires that the low-molecular-weight over-sulfated polysaccharide have a molecular weight of between about 5,000 to 16,000 g/mol. Claim 15, however, recites that the low-molecular-weight over-sulfated polysaccharide has a molecular weight of between about 3 kDa and about 7 kDa or between about 4 kDa and about 6 kDa. Since 1 kDa = 1,000 g/mol, the recited range of about 3 kDa to about 7 kDa extends below the lower limit required by claim 12, and therefore does not further limit claim 12. 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 § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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 12 and 15 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Batzios et al. (JMD Reports, 2011, page 59 – 66, cited in the previous Office Action mailed August 5, 2025) in view of Martins et al. (Brain, 2015, Vol. 138, Issue 2, page 336 – 355, cited in the previous Office Action mailed August 5, 2025), Senni et al. (Marine Drugs, 2011, Vol. 9, Issue 9, page 1664 – 1681, cited in the previous Office Action mailed August 5, 2025), Colliec-Jouault et al. (WO2017/055310A1, cited in the previous Office Action mailed August 5, 2025), , and Poupard et al. (Carbohydrate Polymers, 2017, Vol. 166, page 156 – 165, cited in the previous Office Action mailed December 30, 2025).
Regarding claims 12 and 15 – 20, Batzios et al. disclose that mucopolysaccharidosis (MPS) represent a heterogeneous group of hereditary disorders, characterized by accumulation of glycosaminoglycans within the lysosomes. The expression and activity of matrix metalloproteinases (MMPs), such as MMP-2, are being studied in the serum of pediatric patients with MPS. It is found that serum activity and protein levels of MMP-2 are significantly increased in patients with MPS IIIB (Abstract). MMPs have been implicated in various processes usually related to inflammation (page 60, Left Col., para. 3). Batzios et al. also explicitly teach that MMPs involve in numerous neuroinflammatory diseases (page 65, Left Col, para. 3).
However, Batzios et al. do not teach administering the low-molecular-weight over-sulfated polysaccharide with anti-heparanase to treat mucopolysaccharidosis by blocking heparanase and restricting toxic lysosomal accumulation of heparan sulfate and Batzios et al. do not teach the method for obtaining the low-molecular-weight over-sulfated polysaccharide derived from GY785 or HE800.
Martins et al. teach that neuroinflammation is one of the symptoms found in patients with MPS IIIA and IIIB (page 349, Right Col., para. 2).
Senni et al. disclose that marine biosphere offers wealthy flora and fauna living in different unusual ecosystems embracing diverse microbial communities including deep-sea hydrothermal (page 1671, para. 4). Deep-sea microorganisms, bacteria and archaea, or the processes they mediate in situ, and the promise of their primary and secondary products present a great interest to biotechnology and a potential for pharmaceutical applications (page 1671, para. 5). Screenings have been performed mainly on mesophilic bacteria rather than on psychrophilic, thermophilic, or hyperthermophilic strains. Up to date, three main genera of polysaccharide-producing bacteria have been identified (page 1672, para. 1). Senni et al. disclose Alteromonas sp. and Vibrio sp. HE800 EPS is the marine bacterial polysaccharide from Vibrio diabolicus bacterium (page 1672, para. 2). Senni et al. also introduce the low molecular weight (<20 kDa) and sulfated polysaccharide with new properties. This derivative is obtained by first depolymerizing the high molecular weight EPS by a free-radical reaction. Then the newly depolymerized EPS is chemically sulfated with pyridine-sulfur trioxide in DMF. The HE800 EPS derivative is structurally close to heparan sulfate. The effect of this HE800 EPS derivative is tested in proliferation assays. Thus, in two-dimensional culture this derivative is capable of stimulating the proliferation of dermal and gingival fibroblasts. Moreover, this derivative can inhibit the secretion of MMPs, such as MMP-2 (page 1673, para. 2). Senni et al. also modify EPS GY785 from Alteromonas infernus to obtain over-sulfated low molecular weight polysaccharides with the aim of promoting biological activities (page 1674, para. 3), wherein the GY785 EPS derivatives are able to inhibit induction of MMPs by inflammatory cytokines (page 1675, para. 2).
Colliec-Jouault et al. disclose a low molecular weight (15 kDa) over-sulfated expolysaccharide (GYS15) prepared from a marine native exopolysaccharide excreted by a mesophilic marine bacterium from a deep-sea hydrothermal environment, and relates the use of this low molecular weight over-sulfated exopolysaccharide for the prevention or inhibition of metastases formation (Abstract). Colliec-Jouault et al. disclose the method of obtaining the low molecular weight over-sulfated exopolysaccharide comprising (a) a step consisting of free-radical depolymerization of a marine native exopolysaccharide (EPS) from the strain GY785 of the Alteromonas genus so as to obtain a depolymerized EPS having a molecular weight of 5,000 to 100,000 g/mol; (b) a subsequent step consisting of sulfation of the depolymerized EPS to obtain an over-sulfated depolymerized EPS, comprising adding to the depolymerized EPS at least one sulfation agent in an amount sufficient to obtain a sulfated polysaccharide having a degree of sulfate-group substitution of between 10% and 45% by weight relative to the total weight of the over-sulfated depolymerized EPS; and (c) a subsequent step consisting of isolating the over-sulfated exopolysaccharide from the over-sulfated depolymerized EPS. The step of isolation is carried out by fractionation, in particular fractionation performed by size exclusion chromatography (page 8, lines 17 – 30; page 10, line 30). Colliec-Jouault et al. also disclose a pharmaceutical composition comprising a therapeutically effective amount of GYS15 and at least one pharmaceutically acceptable carrier or excipient (page 5, line 5). The disclosed degree of substitution between 10% and 45% is within the claimed range of 10 – 55% rendering the range of claim 1 obvious. The disclosed 15kDa of the low-molecular-weight over-sulfate polysaccharide is also within the claimed 5,000 – 16,000 g/mol, rendering the claimed range obvious. (See MPEP 2144.05 I).
Poupard et al. teach that low molecular weight sulfated polysaccharide can be engineered to retain anti-heparanase activity while exhibiting minimal or negligible anticoagulant activity, and that such properties are achieved by adjusting molecular weight and sulfation characteristics. Poupard et al. disclose the preparation of low molecular weight sulfated polysaccharide derivatives. The candidate LMW glycol-split λ-carrageenan displays major anti-heparanase properties, with an IC50 of 7.32 ng/mL and a close-to-zero anticoagulant activity (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to target the inhibition of MMPs when treating neuroinflammation in patients with mucopolysaccharidosis as taught by Batzios et al. and Martins et al. by administering a low-molecular-weight over-sulfated polysaccharide derived from GY785 or HE800 in view of Senni et al. and as obtained by the process of Colliec-Jouault et al. because Batzios et al. and Martins et al. teach the relevant MPS III disease context, Senni et al. teach the known biological activity of such marine EPS derivative. One would have been motivated to target the inhibition of MMPs when treating neuroinflammation in patients with mucopolysaccharidosis as taught by Batzios et al. and Martins et al. by administering a low-molecular-weight over-sulfated polysaccharide derived from GY785 or HE800 in view of Senni et al. and as obtained by the process of Colliec-Jouault et al. because Senni et al. teach that both derivatives of GY785 and HE800 exhibit the inhibition of MMPs and Batzios et al. and Martins et al. teach that MMPs cause neuroinflammation in patients with MPS IIIA and IIIB. One of ordinary skill in the art would have had a reasonable expectation of success to target the inhibition of MMPs when treating neuroinflammation in patients with mucopolysaccharidosis as taught by Batzios et al. and Martins et al. by administering a low-molecular-weight over-sulfated polysaccharide derived from GY785 or HE800 in view of Senni et al. and as obtained by the process of Colliec-Jouault et al. because Batzios et al. teach that MMP-2 levels are significantly increased in patients with MPS IIIA and IIIB and that MMPs are implicated in neuroinflammatory processes, Martins et al. teach that patients with MPS IIIA and IIIB exhibit neuroinflammation, Senni et al. teach that derivatives of both GY785 and HE800 inhibit MMP activity or secretion. Thus, the applied references would have suggested that administration of the known marine EPS derivatives of Senni et al. would provide a predictable therapeutic benefit in the MPS III patient population as taught by Batzios et al.
It would have been obvious for one of ordinary skill in the art to modify the low-molecular-weight over-sulfated polysaccharides derived from GY785 or HE800 as taught by Senni et al. with the explicitly stated process in view of Colliec-Jouault et al. because Senni et al. teach marine EPS derivatives from both GY785 and HE800 and Colliec-Jouault et al. teach a detail process, which overlaps with Senni et al., for obtaining a low-molecular-weight over-sulfated polysaccharide, including free-radical depolymerization followed by sulfation, such that substitution or combination would have yielded predictable results. Moreover, Poupard et al. teach that low molecular weight sulfated polysaccharides possess anti-heparanase activity while exhibiting minimal or negligible anticoagulant activity. Therefore, a person of ordinary skill in the art would have recognized the low-molecular-weight over-sulfated polysaccharides derived from GY785 or HE800 as taught by Senni et al. and obtained by the process of Colliec-Jouault et al. also exhibit anti-heparanase activity. The disclosure of the applied references meet all structural limitation of the claimed method and would achieve the same intended results, including “blocking heparanase” and “restricting toxic lysosomal accumulation of heparan sulfate”. One of the ordinary skill in the art would have had a reasonable expectation of success to modify the low-molecular-weight over-sulfated polysaccharides derived from GY785 or HE800 as taught by Senni et al. with the explicitly stated process in view of Colliec-Jouault et al. to achieve the claimed low molecular weight over-sulfated polysaccharide from GY785 or HE800 because Senni et al. teach marine EPS derivatives from both GY785 and HE800 and Colliec-Jouault et al. teach an overlapping process for obtaining low-molecular-weight over-sulfated polysaccharides, including free-radical depolymerization followed by sulfation and isolation, such that substitution or combination would have yielded predictable results.
Regarding claims 15 – 16, one would have considered the ranges of the molecular weight and the degree of sulfate-group substitution disclosed by the combination of applied references as a starting point and would have performed a routine experimentation to determine the optimal weight and degree of substitution because Poupard et al. teach that molecular weight and degree of sulfate-group substitution are recognized result effect variables to obtain the desired anti-heparanase activity. (See MPEP 2144.05 IIA).
Claims 21 – 22 are rejected under 35 U.S.C. 103 as being unpatentable over Batzios et al. (JMD Reports, 2011, page 59 – 66, cited in the previous Office Action mailed August 5, 2025) in view of Martins et al. (Brain, 2015, Vol. 138, Issue 2, page 336 – 355, cited in the previous Office Action mailed August 5, 2025), Senni et al. (Marine Drugs, 2011, Vol. 9, Issue 9, page 1664 – 1681, cited in the previous Office Action mailed August 5, 2025), Colliec-Jouault et al. (WO2017/055310A1, cited in the previous Office Action mailed August 5, 2025), , and Poupard et al. (Carbohydrate Polymers, 2017, Vol. 166, page 156 – 165, cited in the previous Office Action mailed December 30, 2025) as applied to claims 12 and 15 – 20 above, and further in view of National MPS Society (A Guide to Understanding MPS III, 2008, cited in the previous Office Action mailed August 5, 2025).
Regarding claims 21 – 22, the references teach the limitations discussed above.
However, these references do not teach the pharmaceutical composition further comprises one or more additional biologically active agents, wherein the additional biological active agent is an anti-seizure medication.
National MPS Society discloses that children with MPS III can have frequent, minor seizures at a later stage of the disease (page 15, Right Col., para. 3). Seizures can usually be prevented or reduced in frequency with conventional anti-seizure medications (page 15, Right Col., para. 5).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical composition comprising the low molecular weight over-sulfated polysaccharide and at least one pharmaceutically acceptable carrier or excipient as taught by Senni et al. and Colliec-Jouault et al. with one or more additional biological active agents, such as anti-seizure medication, in view of National MPS Society because National MPS Society teaches that seizures are common symptom found in patients with MPS III. It would have been obvious for one of ordinary skill in the art to do this because it is well known to combine drugs to treat different symptoms of the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to combine the pharmaceutical composition comprising the low molecular weight over-sulfated polysaccharide and at least one pharmaceutically acceptable carrier or excipient as taught by Senni et al. and Colliec-Jouault et al. with one or more additional biological active agents, such as anti-seizure medication, in view of National MPS Society because it is well known to combine drugs to treat the same disease.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed March 25, 2026, have been fully considered and are found to be not persuasive.
With the newly added limitations “blocking heparanase” and “restricting toxic lysosomal accumulation of heparan sulfate”, Applicant argues that the cited art in combination fail to teach or suggest the claimed invention as a whole and fail to provide a reasonable expectation of success for achieving the claimed structural and functional profile because the combination of references teaches a treatment pathway for reducing symptoms related to mucopolysaccharidosis, but does not teach the claimed treatment pathway, which is reducing toxic lysosomal accumulation. However, these arguments are not persuasive because the current rejection is based on the combined teachings of Batzios et al., Martins et al., Senni et al., Colliec-Jouault et al., and Poupard et al. and not any single reference alone. Senni et al. and Colliec-Jouault et al. teach the claimed low molecular weight over-sulfated marine polysaccharide and the process for obtaining it. Batzios et al. and Martins et al. teach that MPS III patients show abnormal MMP-related inflammatory biology, and MPS IIIA/IIIB are associated with neuroinflammation, which provide the motivation for treating neuroinflammation in patient with mucopolysaccharidosis by administering the low-molecular-weight over-sulfated polysaccharides derived from HE800. Poupard et al. teach that low molecular weight sulfated polysaccharide may be engineered to retain anti-heparanase activity through control of molecular weight and sulfation characteristics. Thus, the combination would have suggested treating MPS with low-molecular-weight over-sulfated polysaccharides derived from HE800 and achieving the same treatment mechanism of “blocking heparanase” and “restricting toxic lysosomal accumulation of heparan sulfate”.
Applicant states that this mechanism is not disclosed in any of the cited documents and experimental evidence is provided in the specification for demonstrating the reduction of toxic lysosomal accumulation using the claimed polysaccharides. Applicant’s reliance on experimental evidence is acknowledged. However, the argument is not persuasive because the combination of the cited references teaches administration of the claimed type of low-molecular-weight over-sulfated polysaccharide having anti-heparanase to the relevant MPS subject. The phrase “restricting toxic lysosomal accumulation of heparan sulfate” is the intended result of administering the recited anti-heparanase composition. Moreover, the evidence in the specification is only viewed as confirming an expected property of the claimed composition. The expectation of success needs only be reasonable, not absolute. Conclusive proof of efficacy is not required. (See MPEP 2143.02 I).
Applicant argues that none of the cited references teaches the polysaccharide with the precise molecular weight and degree of sulfate-group substitution that would achieve the desired biological activity and homogeneity. However, the argument is not persuasive. Colliec-Jouault et al. teach the free-radical depolymerization and sulfation process for obtaining low molecular weight over-sulfated exopolysaccharides, including a molecular weight range of 5000 to 100,000 g/mol and sulfate-group substitution values within the claimed range and Poupard et al. teach that anti-heparanase activity in low molecular weight sulfated polysaccharides depends on molecular weight and sulfation characteristics. Therefore, molecular weight and sulfation level are result-effective variables and selecting workable values within the ranges taught by the art would have been a routine optimization. Applicant may overcome routine optimization rejections by showing that the claimed range is critical. (See MPEP 2144.05 IIIA).
Regarding Poupard et al., Applicant argues that Poupard et al. do not disclose the treatment of mucopolysaccharidosis by blocking heparanase and therefore restricting toxic lysosomal accumulation of heparin sulfate. However, the argument is not persuasive because the rejection does not rely on Poupard et al. alone for that teaching. Poupard et al. is relied upon for the teaching that low molecular weight sulfated polysaccharides possess anti-heparanase activity. As discussed above, Batzios et al. teach that MMP-2 levels are significantly increased in patients with MPS IIIA and IIIB and that MMPs are implicated in neuroinflammatory processes, Martins et al. teach that patients with MPS IIIA and IIIB exhibit neuroinflammation, Senni et al. teach that derivatives of both GY785 and HE800 inhibit MMP activity or secretion. Thus, the combination of Batzios et al. in view of Martins, Senni et al., Colliec-Jouault et al., and Poupard et al. meets all structural limitation of the claimed method and would achieve the same intended results, including “blocking heparanase” and “restricting toxic lysosomal accumulation of heparan sulfate”.
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 12 and 17 – 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7 of U.S. Patent No. 11219638B2 in view of Senni et al. (Marine Drugs, 2011, Vol. 9, Issue 9, page 1664 – 1681, cited in the previous Office Action mailed August 5, 2025) and Batzios et al. (JMD Reports, 2011, page 59 – 66, cited in the previous Office Action mailed August 5, 2025) and Martins et al. (Brain, 2015, Vol. 138, Issue 2, page 336 – 355, cited in the previous Office Action mailed August 5, 2025), and Poupard et al. (Carbohydrate Polymers, 2017, Vol. 166, page 156 – 165, cited in the previous Office Action mailed December 30, 2025).
Regarding claims 12 and 17 – 19, ‘638B2 teaches a method for inhibiting osteosarcoma-induced metastases formation in an osteosarcoma patient, comprising a step of administering to said osteosarcoma patient a therapeutically effective amount of a 15 kDa over-sulfated exopolysaccharide, wherein said 15 kDa over-sulfated exopolysaccharide is obtained by a method comprising the following steps: (a) a step consisting of free-radical depolymerization of a marine native exopolysaccharide (EPS) from the strain GY785 of the Alteromonas genus so as to obtain a depolymerized EPS having a molecular weight of 5,000 to 100,000 g/mol; (b) a subsequent step consisting of sulfation of the depolymerized EPS to obtain an over-sulfated depolymerized EPS, comprising adding to the depolymerized EPS at least one sulfation agent in an amount sufficient to obtain a sulfated polysaccharide having a degree of sulfate-group substitution of between 10% and 45% by weight relative to the total weight of the over-sulfated depolymerized EPS; and (c) a subsequent step consisting of isolating the over-sulfated exopolysaccharide from the over-sulfated depolymerized EPS (claim 1). The step of isolation is carried out by fractionation (claim 2), wherein the fractionation is performed by size exclusion chromatography (claim 6).
However, ‘638B2 does not teach the low molecular weight over-sulfated polysaccharide is being used to treat mucopolysaccharidosis, such as MPS type IIIB. ‘638B2 also does not teach the treatment by blocking heparanase and restricting toxic lysosomal accumulation of heparan sulfate.
The teachings of Senni et al. are as discussed above.
The teachings of Batzios et al. are as discussed above.
The teachings of Martins et al. are as discussed above.The teachings of Poupard et al. are as discussed above.It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to repurpose the derivative of GY785 EPS as taught by ‘638B2 based on its known biological activities, such as the inhibition of the induction of MMPs, in view of Senni et al. to treat mucopolysaccharidosis, further in view of Batzios et al., Martins et al., and Poupard et al. because Batzios et al. teach that protein levels of MMP-2 are significantly increased in patients with MPS III, whereas MMPs are known to be involved in neuroinflammation, Martins et al. teach that patients with MPS IIIA and IIIB exhibit signs of neuroinflammation, and Poupard et al. teach that low molecular weight sulfated polysaccharides possess anti-heparanase activity while exhibiting minimal or negligible anticoagulant activity. Therefore, a person of ordinary skill in the art would have recognized the low-molecular-weight over-sulfated polysaccharides derived from GY785 as taught by ‘638B2 also exhibit anti-heparanase activity. The disclosure of the applied references meet all structural limitation of the claimed method and would achieve the same intended results, including “blocking heparanase” and “restricting toxic lysosomal accumulation of heparan sulfate”. It would have been prima facie obvious for a person of ordinary skill in the art to substitute GY785 as taught by ‘638B2 with HE800 in view of Senni et al. because Senni et al. teach that both GY785 and HE800 are able to inhibit the levels of MMPs. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to repurpose the derivative of GY785 EPS as taught by ‘638B2 based on its known biological activities, such as the inhibition of the induction of MMPs, in view of Senni et al. to treat mucopolysaccharidosis, further in view of Batzios et al., Martins et al., and Poupard et al. and to substitute GY785 as taught by ‘638B2 with HE800 because Batzios et al. and Martins et al. provide the possible reason for the symptom of MPS, ‘638B2 and Senni et al. disclose the process for making the low molecular weight over-sulfated polysaccharides and their therapeutic benefits, and Poupard et al. teach that low molecular weight sulfated polysaccharides possess anti-heparanase activity.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed March 25, 2026, have been fully considered and are not found to be persuasive.
Regarding the rejection, Applicant requests that the Office hold the double patenting rejection in abeyance until such time as the application is otherwise found to be allowable or the double patenting rejection is rendered moot. As no allowable subject matter has been identified, the double patenting rejection is maintained.
Conclusion
No claim is found to be allowable.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SCARLETT GOON can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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