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 .
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.
This office action is a response to applicant’s response to election submitted October 1, 2025. The claims filed January 28, 2022 are examined herein wherein claims 3-5, 7-15, and 18 were preliminarily amended, claim 2 was cancelled, and claims 19-41 were added. This application is a 371 of PCT/US2020/044449 filed July 31, 2020 and claims benefit of US provisional applications 63/032,680 05/31/2020 filed May 31, 2020, 62/910,738 filed October 4, 2019, and 62/881,307 filed July 31, 2019.
Claims 1 and 3-41 are pending in this application.
Election
Applicant’s election without traverse of the following E-selectin inhibitor:
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and the condition “a transplant recipient” in the reply filed on October 1, 2025 is acknowledged. In the election requirement, Applicant was supposed to specify a hematological disease chosen from malignant and non-malignant diseases, however in order to facilitate compact prosecution, Applicant’s election of transplant recipient is found to be sufficient.
Claims 12, 19-21, 29-31, and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 1, 2025.
Claims 1, 3-11, 13-18, 22-28, 32-34, and 36-41 are encompassed by the elected species and examined herein.
Claim Interpretation
Claim 25 recites “The method according to claim 22, wherein the method further comprises inhibiting sinusoidal obstruction syndrome (SOS) in the subject.” Claim 26 recites “The method according to claim 25, wherein the SOS is a hepatic veno-occlusive disease.”. Bonifazi (Front. Immunol., 2020, cited on PTO-892), Hepatic veno-occlusive disease (VOD) is also known as sinusoidal obstruction syndrome (SOS) (pg. 1, para. 1). The instant specification also recites this (pg. 246, para. 0489). Thus, wherein a prior art teaches the inhibition of either VOD or SOS, both are encompassed.
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.
Claim 26 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.
Regarding claim 26: Claim 26 which depends from claim 25 recites, “wherein the SOS is a hepatic veno-occlusive disease”. However, according to Bonifazi (Front. Immunol., 2020, cited on PTO-892), Hepatic veno-occlusive disease (VOD) is also known as sinusoidal obstruction syndrome (SOS) (pg. 1, para. 1). The instant specification also recites this (pg. 246, para. 0489). Thus, wherein claim 25 recites wherein SOS is inhibited, it necessarily limits wherein VOD is inhibited, given that the two are synonymous. In short, claim 26 does not further limit claim 25 by use of synonyms.
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 22-24 and 27-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Winkler (Blood, 2014, IDS filed February 13, 2023) as evidenced by Li (Cell Chemical Biology, 2018, cited on PTO-892).
Regarding claims 22-24 and 27-28: Winkler teaches the therapeutic blockade of E-selectin in vivo specifically augments the mobilization of HSC with highest self-renewal potential following G-CSF administration and markedly improves subsequent engraftment and reconstitution in mice (pg. 2, para. 1). Winkler teaches the administration of E-selectin inhibitor GMI-1271 (pg. 2, para. 2). Li discloses that GMI-1271 has the following structure:
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, which is identical to the elected species (pg. 501, figure 2A). Winkler teaches that administration of the E-selectin antagonist with G-CSF during HSC mobilization to improve short- and long-term engraftment, thus accelerate recovery in transplant recipients (pg. 3, para. 2).
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, 3-11, 13-18, 22-24, 27-28, 32-34, and 36-41 are rejected under 35 U.S.C. 103 as being unpatentable over Magnani (US 9,867,841, IDS filed February 13, 2023) in view of Winkler (Blood, 2014, IDS filed February 13, 2023), and Winkler (Nature Medicine, 2012, IDS filed February 13, 2023) as evidenced by Li (Cell Chemical Biology, 2018, cited on PTO-892).
Regarding claims 1, 3-8, 10-11, 13-18, 22-24, 27-28, 33-34, and 36-41: Magnani teaches methods for use of E-selectin antagonists for mobilizing cells, such as hematopoietic cells, hematopoietic stem cells and progenitor cells, white blood cells, and malignant cells, and hematopoietic tumor cells from the bone marrow (abstract). More specifically, methods are provided for using E-selectin antagonists including, for example, glycomimetic compounds, antibodies, aptamers, and peptides for mobilizing cells from the bone marrow to the peripheral vasculature and tissues (abstract). Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the peripheral blood or the bone marrow and used for repopulating hematopoiesis (col. 1, lines 25-31). The methods and E-selectin antagonists described herein are therefore useful for treating hematologic malignancies and metastatic disease, particularly in combination or as an adjunct therapy with chemotherapy and/or radiation therapy (col. 39, lines 39-43). The phrase treatment necessarily improves overall survival of the subject (col. 41, lines 16-50). Administration of compound 25 results in improved mobilization in the blood (col. 56, lines 5-10). Compound 25 has the following structure:
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, which is identical to the elected species (Drawings pg. 4, figure 1D).
Magnani does not specifically teach a method of administering the e-selectin antagonist to a subject for increasing survival, engraftment, reconstitution, and quiescence in a subject undergoing HSC transplantation.
However Magnani suggests the method of mobilizing stem cells and progenitors cells can be utilized to treat a recipient subject (i.e. transplant recipient) with Hodgkin lymphoma or aplastic anemia (col. 39, 44-65, col. 40). Winkler (Blood, 2014) discloses the therapeutic blockade of E-selectin in vivo specifically augments the mobilization of HSC with highest self-renewal potential following G-CSF administration and markedly improves subsequent engraftment and reconstitution in mice (pg. 2, para. 1). Winkler (Blood, 2014) teaches the administration of E-selectin inhibitor GMI-1271 (pg. 2, para. 2). Li discloses that GMI-1271 has the following structure:
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, which is identical to the elected species (pg. 501, figure 2A). Winkler (Blood, 2014) discloses the therapeutic blockade of E-selectin in vivo specifically augments the mobilization of HSC with highest self-renewal potential following G-CSF administration and markedly improves subsequent engraftment and reconstitution in mice (pg. 2, para. 1). Winkler (Nature Medicine, 2012) teaches that bone marrow transplant recipients that are pretreated with E-selectin antagonists increase the self-renewal capacity of HSCs (pg. 1654, col. 2, para. 1). Winkler (Nature Medicine, 2012) teaches that e-selectin antagonists promotes HSC quiescence and chemoresistance (pg. 1656, col. 1, para. 2).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to apply the method of mobilizing HSCs of Magnani to a subject undergoing HSC transplantation. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as HSC transplantation is a known technique for treating diseases, such as Hodgkin lymphoma or aplastic anemia, and E-selectin antagonists would be beneficial in improving self-renewal, thereby improving the efficacy of the treatment, improving overall survival. Given that the art establishes e-selectin antagonists results in increasing engraftment, reconstitution, and quiescence, wherein the art establishes it would have been obvious to administer to HSC transplant recipients, these properties flow naturally as a result of practicing the method.
Regarding claims 9 and 32: As discussed above, the prior art renders obvious the methods of claims 7 and 27 above.
Magnani does not teach wherein the subject has depleted and/or compromised bone marrow.
However, Winkler (Nature Medicine, 2012) teaches that chemotherapy-induced bone marrow suppression (i.e. compromised bone marrow) remains a clinical problem and reducing the myelosuppressive effective of chemotherapy could result in less infection and a less of a requirement for blood product and hospital support (pg. 1656, col. 2, para. 3). Winkler (Nature Medicine, 2012) suggests E-selectin antagonism as a treatment for protection of HSCs, improving self-renewal, during chemotherapy or irradiation, thereby overcoming bone marrow suppression (abstract, pg. 1653, col. 1, para. 1).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Magnani for the treatment of subjects with compromised bone marrow as suggested by Winkler (Nature Medicine, 2012). A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as e-selectin antagonists are recognized as improving HSC self-renewal which is a known approach to overcoming bone marrow suppression (i.e. compromised bone marrow) as a result of repeated rounds of chemotherapy or irradiation in patients.
Claims 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Magnani (US 9,867,841, IDS filed February 13, 2023) Winkler (Blood, 2014, IDS filed February 13, 2023), Winkler (Nature Medicine, 2012, IDS filed February 13, 2023), and Li (Cell Chemical Biology, 2018, cited on PTO-892), as applied to claims 1, 3-11, 13-18, 22-24, 27-28, 32-34, and 36-41 above, further in view of Oancea (Gastroenterology, 2016, IDS filed February 13, 2023) and Oancea (Gut, 2013, IDS filed February 13, 2023).
Regarding claims 25-26: As discussed above, Winkler teaches the method of claim 22.
Winkler does not teach or suggest wherein the method further comprises inhibiting SOS or hepatic veno-occlusive disease (VOD). The Examiner notes that as discussed above in the claim interpretation section above, these are synonymous terms.
However, Oancea (Gastroenterology, 2016) teaches that E-selectin antagonist GMI-1271 (i.e. the claimed compound) alleviates acute liver injury caused by drug induced toxicity that increases surface expression of E-selectin (pg. S-1029, col. 2, abstract 358). Oancea (Gut, 2013) teaches that antileukemic drugs can cause hepatic veno-occlusive disease/sinusoidal obstructive syndrome (abstract). Oancea (Gut, 2013) teaches that inhibition of E-selectin expression can reduce SOS by abrogating the influx and activation of inflammatory cells into the liver, suggesting a therapeutic approach to alleviation of SOS-VOD due to anti-leukemic drugs (pg. 604, col. 1, para. 3).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to apply the method of Winkler for the inhibition of SOS or VOD as suggested by Oancea (Gastroenterology, 2016) and Oancea (Gut, 2013). A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that the art establishes a correlation between the inhibition of E-selectin with a reduction in these conditions. A person of ordinary skill in the art would have the motivation to reduce these conditions as a result of hepatoxicity resulting from patients undergoing treatment with anti-leukemic drugs.
Conclusion
No claims are allowed in this action.
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/S.L.G./Examiner, Art Unit 1693
/ERIC OLSON/Primary Examiner, Art Unit 1693