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 .
This is the first action on the merits.
Election/Restrictions
Applicant's election without traverse of Group (III) in the reply filed on June 3, 2026 is acknowledged. Group (III), drawn to a method of synthesizing ruxolitinib phosphate utilizing the compound of formula (14), embraced by claims 1-13 was elected by Applicant. Applicant has not pointed to any errors in the Examiner’s analysis of the different inventions. The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claim 5 is objected to because of the following informalities: the term “novel” should be removed from b). Appropriate correction is required.
Claims 6 and 7 are objected to because of the following informalities: the term “and” should be added between the two steps. Appropriate correction is required.
Claims 7 and 9 are objected to because of the following informalities: the term “or” should be added between the last two groups in claim 7, step b); and claim 9, step d), step d), step f) and step h). Appropriate correction is required.
Claim 11 is objected to because of the following informalities: a period is missing at the end of the claim. Appropriate correction is required.
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 6 and 9 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 pre-AIA the applicant regards as the invention.
Regarding claim 6, the phrase “the organic solvent” in step a) lacks antecedent basis.
In claim 9, the phrase “the organic solvent” in step e) lacks antecedent basis since this should be a mixture based on claim 5.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 5-13 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Zhou et al. (US 8410265) in view of Zhou et al. (WO 2010083283) and Rajan et al. (WO 2016063294).
The present application claims a method of making ruxolitinib phosphate of formula (I),
PNG
media_image1.png
222
233
media_image1.png
Greyscale
by the following sequence of reactions:
[AltContent: textbox ([img-media_image2.png])][AltContent: textbox (SEM-Cl,
Base, solvent)][AltContent: arrow]a)
PNG
media_image3.png
110
152
media_image3.png
Greyscale
PNG
media_image4.png
95
99
media_image4.png
Greyscale
[AltContent: arrow][AltContent: textbox (Pd catalyst,
aq organic solvent)]b)
PNG
media_image4.png
95
99
media_image4.png
Greyscale
PNG
media_image5.png
140
90
media_image5.png
Greyscale
[AltContent: arrow][AltContent: textbox (Acid,
base)]c)
PNG
media_image5.png
140
90
media_image5.png
Greyscale
PNG
media_image6.png
143
144
media_image6.png
Greyscale
[AltContent: textbox (Base, organic solvent)][AltContent: textbox ([img-media_image7.png])][AltContent: arrow]d)
PNG
media_image6.png
143
144
media_image6.png
Greyscale
PNG
media_image8.png
159
85
media_image8.png
Greyscale
[AltContent: textbox (1)DBTA,
2)crystallization)][AltContent: arrow]e)
PNG
media_image8.png
159
85
media_image8.png
Greyscale
PNG
media_image9.png
219
143
media_image9.png
Greyscale
[AltContent: textbox (Boron trifluoride etherate, organic solvent)][AltContent: arrow]f)
PNG
media_image9.png
219
143
media_image9.png
Greyscale
PNG
media_image10.png
183
105
media_image10.png
Greyscale
[AltContent: textbox (1)base,
2)DBTA)][AltContent: arrow]g)
PNG
media_image10.png
183
105
media_image10.png
Greyscale
PNG
media_image11.png
199
153
media_image11.png
Greyscale
[AltContent: textbox (phosphoric acid,
solvent)][AltContent: arrow]h)
PNG
media_image11.png
199
153
media_image11.png
Greyscale
PNG
media_image1.png
222
233
media_image1.png
Greyscale
i) purification of the compound of formula (I); and
[AltContent: arrow][AltContent: textbox (Repeat steps d)-h))]j) found in claim 11-13,
PNG
media_image9.png
219
143
media_image9.png
Greyscale
+ the (S) enantiomer
PNG
media_image6.png
143
144
media_image6.png
Greyscale
.
Zhou et al. teaches a method of making ruxolitinib phosphate of formula (I), wherein step a) is found in column 157.
The Suzuki coupling of step b) is found in column 158 and is done with a different boronic compound, as shown here
PNG
media_image12.png
93
376
media_image12.png
Greyscale
. However, the reference in column 14 teaches the equivalency of the boronic compounds, see the small genus of formula (XIII). Moreover, this reaction is done in a base where the boronic compound may form a salt in situ. Thus, the compounds are similar with similar properties.
Rajan et al. also teaches a method of making ruxolitinib phosphate of formula (I), with a Suzuki coupling reaction:
PNG
media_image13.png
205
491
media_image13.png
Greyscale
, see page 48.
This also shows the equivalency of the boronic compounds.
Zhou further teaches step c) in column 158; step d) in columns 159-160; and step e) column 162.
The reference further teaches step f) without the DBTA salt, see column 144. There is no evidence in the specification that the product from step e), the DBTA salt, survives the lewis acid treatment with BF3-etherate, which is not characterized as noted on page 24 of the present specification. Since the product from step e) is not isolated, step e) seems to increase the number of steps for the synthesis, especially since a base and DBTA treatment follow in step g).
Step g) is found in column 144, but not as the DBTA salt, where the same rationale above applies here for the DBTA salt; and this step is similar to step e) for the DBTA step, found in column 162 of the reference.
Rajan teaches the conversion of the chiral acid salt to the phosphoric acid final product:
PNG
media_image14.png
481
342
media_image14.png
Greyscale
, see page 48.
Step i) is found in column 152 of the Zhou reference, provides a purification step.
The ‘283 reference provides many of the steps discussed above, see pages 15, 224, 227, 230 and scheme 14. The reference also shows step h) on page 184, where the free compound (not DBTA salt) is converted to the phosphoric acid salt.
Rajan et al. teaches a similar reaction found in claim 11:
PNG
media_image15.png
272
330
media_image15.png
Greyscale
PNG
media_image16.png
79
279
media_image16.png
Greyscale
PNG
media_image17.png
238
325
media_image17.png
Greyscale
, see page 48, Scheme II, and pages 60-61, compound 17, where the group on the pyrazole ring is removed with and acid/base treatment. The differences are 1) the methyl group versus Applicant’s cyclopentyl; and 2) the SO2-phenyl-4-methyl group versus Applicant’s H. Neither of these two groups participate in the reaction. The use of analogous reactants in a known process is prima facie obvious. In re Durden, 226 USPQ 359 (1985). Once the general reaction has been shown to be old, the burden is on Applicants to present reasons or authority for believing that a group on the starting material would take part in or affect the basic reaction and thus alter the nature of the product or the operability of the process.
Recycling and recovering materials during a manufacturing process is always a consideration since businesses are always trying to find ways to reduce waste and save money.
In looking at the instant claimed process as a whole, as stated in In re Ochiai, 37 USPQ 2d 1127 (1995), the claimed process would have been suggested to one skilled in the art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached on 571-272-9023. 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.
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
Prosecution Insights