DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 13 February 2026 in which claims 52 was canceled, claims 51, 53, 59-61, 63-66 and 72 were amended to change the scope and breadth of the claims, and 77 was newly added.
Claims 51 and 53-77 are pending in the current application. Claims 54-55 remain withdrawn as being drawn to a non-elected invention. Claims 51, 53, and 56-77 are examined on the merits herein.
The Declaration of Dr. Guillermo Franco Rodriguez, submitted by Applicant on 13 February 2026 under 37 CFR §1.132 are acknowledged and will be further discussed below.
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 .
Withdrawn Rejections
Applicant’s amendment, filed 13 February 2026, with respect to the objection of claims 51-53 and 56-76, has been fully considered and is persuasive because the claims have been amended to replace “mol.” with “mol”. The objection is hereby withdrawn.
Applicant’s amendment, filed 13 February 2026, with respect to the rejection of claims 52, 53, 59, 60, 61, 63, 66 and 72 under 35 U.S.C. § 112(b), second paragraph, for indefiniteness, has been fully considered and is persuasive.
Claim 52 has been canceled.
Claim 53 has been amended to depend from claim 51.
Claims 59, 61, 63, 66 and 72 have been amended to delete all instances of “at least”.
Claim 60 has been amended to depend from claim 57.
The rejections are hereby withdrawn.
Applicant’s amendment, filed 13 February 2026, with respect to the rejection of claims 51, 56-61 and 65-76 under 35 U.S.C. § 102(a)(1)/(a)(2) as being anticipated by Rodriguez et al., has been fully considered and is persuasive.
Claims 51 and 65 has been amended to recite “exhibiting a 1,6-anhydro residue content of about 1-15% at the reducing terminus of its oligosaccharide chains”, and “a molar ratio of 1,6-anhydroglucosamine residues:1,6-anhydromannosamine residues that is greater than or equal to about 1:1”. These features are not expressly disclosed by Rodriguez et al., and it is not clearly an inherent feature of the products obtained by Rodriguez et al.
The rejection is hereby withdrawn.
Applicant’s amendment, filed 13 February 2026, with respect to the rejection of claims 51, 53, 56-61 and 65-76 under 35 U.S.C. § 102(a)(1) as being anticipated by Xu et al., has been fully considered and is persuasive.
Claims 51 and 65 has been amended to recite “exhibiting a 1,6-anhydro residue content of about 1-15% at the reducing terminus of its oligosaccharide chains”, and “a molar ratio of 1,6-anhydroglucosamine residues:1,6-anhydromannosamine residues that is greater than or equal to about 1:1”. These features are not expressly disclosed by Xu et al., and it is not clearly an inherent feature of the products obtained by Xu et al.
The rejection is hereby withdrawn.
Applicant’s amendment, arguments and Declaration, filed 13 February 2026, with respect to the rejection of claims 51-53 and 56-76 under 35 U.S.C. § 103 as being unpatentable over Rodriguez et al. in view of Jeske et al. and Guan et al.; and the rejection of claims 51-53 and 56-76 under 35 U.S.C. § 103 as being unpatentable over Rodriguez et al. in view of Xu et al., Jeske et al. and Guan et al., has been fully considered and is persuasive.
Independent claims 51, 62, 65 and 77 recite “exhibiting a 1,6-anhydro residue content of about 1-15% at the reducing terminus of its oligosaccharide chains”, and “a molar ratio of 1,6-anhydroglucosamine residues:1,6-anhydromannosamine residues that is greater than or equal to about 1:1”.
These features in combination with the other limitations claimed, are not expressly disclosed by Rodriguez et al. or Xu et al. On pages 10-11 of the remarks filed 13 February 2026, Applicant argues the teachings of Rodriguez, Jeske and Guan and the teachings of Rodriguez, Xu, Jeske and Guan would be improper to combine.
Applicant argues Rodriguez et al. require a phosphazene base or guanidine-base for depolymerization. This argument is true, and in fact, upon further consideration, it is noted Rodriguez et al. teach away from using Triton B, a quaternary ammonium hydroxide base because it resulted in the formation of a heparin product having lower activity than heparin prepared from a phosphazene or guanidine base (see example 4 of Rodriguez et al.). Additionally, it resulted in a product having a MW outside the range presently claimed.
Applicant also argues Jeske et al. is silent about the base used to produce a product having 1,6-anhydromannosamine and/or 1,6-anhydroglucosamine. Thus, one of ordinary skill in the art would not have known how to modify the alkaline conditions of Jeske et al. to arrive at a heparin having 1-15% 1,6-anhydro content with a reasonable expectation of success.
Applicant argues Guan et al. requires sodium hydroxide, and that one of ordinary skill in the art would not have replaced the sodium hydroxide of Guan et al. with the phosphazene base or guanidine-derived base of Rodriguez, because doing so would be contrary to the teaching of Guan et al. Applicant also argues the skilled artisan would not have been motivated to replace the phosphazene base or guanidine-derived base of Rodriguez et al. with the sodium hydroxide of Guan et al., because doing so would be contrary to the teaching of Rodriguez et al.
The above arguments are found persuasive. Rodriguez et al. expressly studied the effect of a phosphazene base, a guanidine-derived base, and a quaternary ammonium hydroxide base and found the quaternary ammonium hydroxide base resulted in an inferior heparin product. It is also important to note, that the molecular weight of the heparin prepared from the quaternary ammonium hydroxide base is outside the range of the present claims, and it is not clear how one would have modified the reaction parameters using the quaternary ammonium hydroxide base to arrive at the claimed product having the structural features presently claimed.
The teaching of the prior art as a whole shows the reaction conditions, including the base used, affects the product prepared. One of ordinary skill in the art would not have been motivated to substitute the sodium hydroxide of Guan et al. with a phosphazene base or guanidine-derived base with a reasonable expectation of success in arriving at a heparin product having the claimed weight average MW, amount and molar ratio of 1,6-anhydroglucosamine, and 1,6-anhydromannosamine.
The rejections are hereby withdrawn.
New & Modified Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on 13 February 2026, where the limitations in pending claims 51, 53, 59-61, 63-66 and 72 as amended now have been changed and claim 77 has been newly added. Therefore, rejections from the previous Office Action, dated 16 September 2025, have been modified and are listed below.
Claim Rejections - 35 USC § 112(b)
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 56, 57, 59, 60, 67, 69-71 and 73-76 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.
Claims 57, 59, 60, 70, 74, 75 and 76 contains the trademark/trade name “Triton B”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982).
The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a reagent used to prepare the claimed LMWH, accordingly, the identification/description is indefinite.
The recitation “said treating” in claim 56 renders the claim herein indefinite. Claim 56 depends from claim 51, which as amended recites “the step of treating quaternary ammonium hydroxide” (in line 6), and “prepared by three treatments of benzalkonium heparin salt” (in line 9). Since claim 51 recites two different treating steps, it is not clear which limitation claim 56 is referring to and further limiting.
Independent claim 65 also recites the term “treatments” and “treating” in two different steps.
Dependent claims 57, 59, 67, 69, 70, 71, 73, and 75 are indefinite for similar reasons as claim 56. These claims depend from claim 51 or 65, both of which recite two different treating steps, such that it is not clear which treating steps the dependent claims are further limiting.
The recitation “depolymerizing heparin to form said depolymerized heparin salt” in claim 57 renders the claim herein indefinite. The “benzalkonium heparin salt” described in independent claim 51 is not described as depolymerized. Instead, it appears the “benzalkonium heparin salt” is depolymerized after it is treated with “a portion of methanol solution of quaternary ammonium hydroxide”.
The recitation “wherein the process further comprises…b) preparing an aqueous solution of heparin sodium” in claim 57 renders the claim herein indefinite. While claim 51 describes preparing a benzalkonium heparin salt, there is no recitation of sodium. And claim 57 does not describe the source of the sodium. It’s not clear how or where “heparin sodium” is formed.
The use of the term “salt” in claim 57, particularly steps b and f are confusing. It’s unclear if this is a heparin sodium salt or benzalkonium heparin salt.
The recitation “the ratio of benzalkonium chloride to heparin sodium is in the range of about 3-6% w/v” in claim 60 renders the claim herein indefinite. A ratio is usually a unitless value, and is not expressed as a percentage. The recitation “3-6% w/v” is a concentration, which could either represent the amount of benzalkonium chloride or heparin sodium”. However, it’s not clear what it encompasses as written.
The recitation “iii) the benzalkonium chloride is present as an about 50% w/v aqueous solution that is added to the solution of step a)” in claim 60 renders the claim herein indefinite. Claim 60 depends from claim 57, and claim 57 step a) does not require adding benzalkonium chloride to the solution of step a. Rather, benzalkonium chloride is added to “an aqueous solution of heparin sodium” in step b.
The recitation “for step d), the temperature is maintained for about 24 hours or more” and “x) the temperature of step d) is maintained at about 25-35°C” in claim 60 renders the claim herein indefinite. Claim 57 step d) does not specify any temperature. It is not clear if Applicant meant to further limit a different step. It is also noted claim 60 uses the step “x)” two different times (see limitation about the amount of hydrogen peroxide in water).
The parenthesis “(about 33% w/v in water)” recited two times in claim 71 renders the claim herein indefinite, because it is not clear if this limitation is required by the claim. The entire phrase should be deleted, or the parenthetical markers should be deleted.
Claim Rejections - 35 USC § 112(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.
Claims 60, 61, 63, 64, 66, 67 and 72 are 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.
The recitation “x) the H-2O2 solution comprises about 30-35% w/v of H2O2 in water” in claim 60 fails to further limit the claims, because claim 51 already requires using H2O2 “which is about 30-35% w/v in water”.
Similarly, the recitation “xi) for each portion of H-2O2 solution added, about 0.04-1.0 liters of the solution is added per Kg of benzalkonium heparinate” in claim 60 fails to further limit the claims, because claim 51 already requires the “depolymerized heparin” which is “benzalkonium heparin salt” be treated with “about 0.04-1 L of H2O2, per Kg of heparin salt”.
The recitation “wherein a) the weight average molecular weight of the LMWH is in the range of about 3-3.8 KDa” in claims 61, 63, 66, and 72 fails to further limit the claims, because claims 51, 62 and 65 already requires LMWH has a weight average MW in the range of about 3-3.8 KDa”.
The recitation “b) the LMWH exhibits a 1,6-anhydro residue content of about 1-15%” in claims 61, 63 and 66 fails to further limit the claims, because claims 51, 62 and 65 already require this feature.
The recitation “c) the LMWH exhibits a molar ratio of 1,6-anhydroglucosamine residues:1,6-anhydromannosamine residues that is greater than or equal to about 1:1” in claims 61, 63, 66 and 72 fails to further limit the claims, because claims 51, 62 and 65 already require this feature.
The recitation “the content of 1,6-anhydroglucosaine residues in the LMWH is less than about 1.1 %mol or in the range of about 0.1-1.1% mol” and “the content of 1,6-anhydromannosamine residues in the LMWH is less than about 1.2% mol or in the range of about 0.05-1.2% mol” in claims 61, 63, 64, 66 and 72 fails to include all the limitations upon which it depends, because it includes values below the range of claims 51, 62 and 65.
Claim 67 fails to further limit claim 65, because it recites all the same limitations in claim 65.
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.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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