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 .
DETAILED ACTION
Status of 18/017,078
Claims 17-20 and 22-31 are currently pending.
Priority
Instant application 18/017,078, filed 1/19/2023, claims priority as follows:
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Receipt of the foreign priority application is acknowledged, and thus, the effective filing date of claims 17-20 and 22-31 is 7/23/2020.
Information Disclosure Statement
All references from the IDS’s submitted on 3/30/2023 and 1/5/2026 have been considered unless marked with a strikethrough.
Objection to the Abstract
The abstract of the disclosure is objected to for minor grammatical informalities. The abstract reads, “invention pertains an inhibitor”, but should read, “invention pertains to an inhibitor”. Additionally, the abstract reads, “an S100 protein” and “an S100A8 or S100A9 protein”, but should read “a S100 protein” and “a S100A8 or S100A9 protein”, and states, “an diagnostic method” but should read “a diagnostic method”. Furthermore, spaces are missing in the words, “orS100A9” and “ortreatment”. Appropriate correction is required.
Objection to Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 1B, 1C, 1D, 2B, 2C, and 2D are not able to be interpreted as they are color coded, yet submitted in black and white. It is unclear what lines and plot points correspond to the labels in the drawings. Furthermore, Figure 4B does not contain a legend for different shaded plot points and is also unable to be interpreted.
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Objection to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 10, line 40. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Election/Restriction
Applicant’s election of the compound tasquinimod, also known as 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethyl)phenyl]-1,2-dihydroquinoline-3-carboxamide:
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with traverse in the reply filed 9/23/2025 is acknowledged. Tasquinimod reads on Formula (I):
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Where R1 is methoxy, R2 is methyl, R3 is trifluoromethyl, and R4 is hydrogen. The traversal argument has been considered but is not found persuasive because the instant application was filed under 35 U.S.C. 371 and is therefore subject to unity of invention analysis, not search burden.
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and no prior art was identified. The Examiner then expanded the scope of the search to encompass all compounds of instant formula (I), and no prior art or double patenting rejections were identified. Thus, the full scope of claims 17-20 and 22-31 are the subject of this Office Action.
Claim Interpretation
Claims 17 and 18 recite “myelofibrosis”, which is not explicitly defined in the disclosure. However, the specification refers to “primary myelofibrosis” and defines the term as, “the prototypic example of progressive development of BM fibrosis” (page 1, lines 17-18). Thus, the term “myelofibrosis” is currently being interpreted as “primary myelofibrosis” or “PMF” in accordance with this definition and the Examples and Results section of the instant specification.
Claim 18 recites the limitation, “a fibrotic phase of the myelofibrosis” and as stated below, the limitation is unclear. However, for examination purposes, the limitation “a fibrotic phase of the myelofibrosis” is currently being interpreted as encompassing both the pre-fibrotic phase of myelofibrosis with absent to minimal fibrosis and the fibrotic phase with marked reticulin or collagen fibrosis found in bone marrow of primary myelofibrosis patients (page 1, lines 30-34).
Claim 27 recites the limitation, “4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethyl)phenyl]-1,2-dihydroquinoline-3-carboxamide”, which is also known in the art as tasquinimod and ABR-215050. Thus, the limitation “4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethyl)phenyl]-1,2-dihydroquinoline-3-carboxamide” is currently being interpreted as any one of these compounds.
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 18-19 and 27 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.
Claim 18 recites the limitation, “a fibrotic phase of the myelofibrosis” in reference to the delaying the onset and/or reducing the progression of myelofibrosis with the inhibitors of the instant claims. However, the instant disclosure does not define what the fibrotic phases of myelofibrosis are and it is not known to one of ordinary skill. In fact, the instant specification defines a singular fibrotic phase with marked reticulin or collagen fibrosis (page 1, lines 30-32) whereas the claim implies there are multiple fibrotic phases. Thus, the limitation is deemed unclear and indefinite. For examination purposes, as stated above, the limitation “a fibrotic phase of the myelofibrosis” is currently being interpreted as encompassing both the pre-fibrotic phase of myelofibrosis with absent to minimal fibrosis and a fibrotic phase with marked reticulin or collagen fibrosis found in bone marrow of primary myelofibrosis patients (page 1, lines 30-34). Dependent claim 19 does not overcome the rejection by defining one of these fibrotic phases. Appropriate correction is required.
Claim 27 recites an instance of parentheses. Specifically, claim 27 recites, “(tasquinimod)” in reference to the compound 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethyl)phenyl]-1,2-dihydroquinoline-3-carboxamide. The phrase within the parentheses is indefinite because it is exemplary language and it is not clear if the contents of the parentheses are required, or just examples of what is required. Appropriate correction is required.
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 19 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 19 recites, “a bone marrow fibrotic phase”, in reference to the fibrotic phase that an inhibitor of the instant claims is delaying the onset and/or reducing the progression in myelofibrosis. However, this claim does not further limit the subject matter recited in claims 17 and 18, from which claim 19 depends, because the specification defines primary myelofibrosis as, “a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material” (page 13, lines 7-9). Thus, the addition of “bone marrow” to the limitation of “fibrotic phase” does not limit the claim because myelofibrosis already occurs in bone marrow.
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.
Close Prior Art
Close prior art identified during the search is Källberg (Källberg, E. et. al. PLOS One. 2012, 7(3), e34207), which discloses the elected species ABR-215050, also known as “tasquinimod”, as a S100A9-binding small molecule (page 2, left column, first paragraph) primarily used for treating prostate cancer. Additionally, Källberg teaches that ABR-215050 inhibits the interaction between S100A9 and TLR4 to inhibit E4 lymphoma growth in mammals (Figure 6) as well as oral administration of ABR-21050 at 30mg/kg/day. However, Källberg fails to teach, alone or in view of the prior art, a nexus between the binding of tasquinimod to S100A9 and treatment of mammals with myelofibrosis. Stated differently, at the time of filing, the prior art does not identify S100A9 as a validated target for treating myelofibrosis and it was unknown if compounds binding S100A9 would produce the desired therapeutic effect in mammals.
Additional close prior art is Björk (Björk, P. et. al. PLOS Biology. 2009, 7(4), e1000097.), which teaches the compound ABR-215757 (Figure 1A):
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that anticipates a compound of instant formula (I):
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when R1 is ethyl, R2 is C2 alkyl, and R3 and R4 are H. The Examiner notes ABR-215757 is also known in the art as paquinimod. Björk teaches S100A9 as the target for compound ABR-215757, and additionally teaches ABR-215757 as able to inhibit acute experimental autoimmune encephalomyelitis in mammals (abstract and page 0807, right hand column). However, Björk does not teach, alone or in combination with the prior art, a nexus between ABR-215757 binding to S100A9 and treatment of mammals with myelofibrosis. Similar to the tasquinimod argument above, the prior art demonstrates that S100A9 was not a validated target in treating myelofibrosis and it was unknown if ABR-215757 binding S100A9 would produce the desired therapeutic effect in mammals.
Claim Objections
Claim 17 recites, “an S100 protein”, but should read “a S100 protein”. Appropriate correction is required.
Claims 20 and 28-31 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 22 recites, “R2” in reference to the substitution of Formula (I), but should recite “R2” to ensure consistency with Formula (I) and variables recited in previous claims.
Claims 23-25 recite, “R3” in reference to the substitution of Formula (I), but should recite “R3” to ensure consistency with Formula (I) and variables recited in previous claims.
Claim 26 recites, “R4” in reference to the substitution of Formula (I), but should recite “R4” to ensure consistency with Formula (I) and variables recited in previous claims.
Conclusion
Claims 18-19 and 27 are rejected. Claims 17, 20, 22-26, and 28-31 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621