DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-10 are pending in the instant invention. According to the In The Claims, filed July 3, 2023, claims 1-8 were amended and claims 9 and 10 were added.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/IB2022/051461, filed February 18, 2022, which claims priority under 35 U.S.C. § 119(a-d) to IT 102021000003887, filed February 19, 2021.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, with traverse, in the reply filed on December 2, 2025, is acknowledged: Group II - claims 1-4, 9 and 10. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
Similarly, the inventor or joint inventor should further note that the traversal is on the grounds that a search and examination of all the claims would not place a serious burden on the Examiner. This is not found persuasive because the multiple inventions in the instant invention are independent or distinct for the reasons disclosed in the Requirement for Restriction / Election of Species, mailed on October 2, 2025.
Likewise, the inventor or joint inventor should further note that there would be a serious burden on the examiner if restriction was not required because the inventions have acquired a separate status in the art due to their divergent subject matter and would require a different field of search.
Next, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Moreover, the inventor or joint inventor should further note that claims 5-8 were withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to a nonelected or cancelled invention, there being no allowable generic or linking claim.
Thus, a first Office action and prosecution on the merits of claims 1-4, 9 and 10 is contained within.
Specification Objection - Disclosure
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the inventor’s or joint inventor’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility invention should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase Not Applicable should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR
DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A
COMPACT DISC.
(f) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art (including information disclosed under 37 CFR 1.97
and 1.98).
(g) BRIEF SUMMARY OF THE INVENTION.
(h) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(i) DETAILED DESCRIPTION OF THE INVENTION.
(j) CLAIM OR CLAIMS (commencing on a separate sheet).
(k) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(l) SEQUENCE LISTING (See MPEP § 2424 and 37 CFR 1.821-1.825).
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(b) above and 37 CFR 1.77(c). Revisions should particularly include and/or address: a) section headings (b-i), where applicable; and b) bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Title
The inventor or joint inventor is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive and should contain fewer than 500 characters. See 37 CFR 1.72(a) and MPEP § 606.
The title of the invention is not technically accurate and descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. In the revised title, the examiner suggests identifying Larotrectinib sulfate of the formula I.
The following title is suggested: PROCESS FOR PEPARING LAROTRECTINIB SULFATE.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
A process for preparing Larotrectinib sulfate of the following formula:
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wherein the process comprises the following steps:
(a) reacting Larotrectinib chloride of the following formula:
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with a base selected from the group consisting of an alkali metal hydroxide and an alkali earth metal hydroxide in the presence of a chlorinated hydrocarbon solvent, to obtain Larotrectinib of the following formula:
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;
(b) reacting the Larotrectinib obtained in step (a) above with sulfuric acid in the presence of methyl ethyl ketone and water, to obtain Larotrectinib sulfate of the following formula:
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; and
(c) filtering the Larotrectinib sulfate obtained in step (b) above.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (a), the alkaline metal hydroxide or alkaline earth metal hydroxide is sodium hydroxide or potassium hydroxide.
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (b), the reaction is performed by dropwise addition of a 40% by weight aqueous sulfuric acid solution into a solution of Larotrectinib in methyl ethyl ketone and demineralized water.
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 3, wherein the ratio of methyl ethyl ketone to demineralized water is 95:5.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (a), the chlorinated hydrocarbon solvent is dichloromethane.
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 2, wherein in step (a), the alkaline metal hydroxide or alkaline earth metal hydroxide is sodium hydroxide.
Appropriate correction is required. See MPEP § 2173.02.
Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claims 1-4, 9 and 10 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 1 recites the functional limitation and/or physicochemical property, A process for preparing Larotrectinib sulfate,... wherein a content of S-Larotrectinib (3-O-sulfo-Larotrectinib) in the Larotrectinib sulfate is less than 0.10% by weight, in lines 1-10 of the claim.
Similarly, the inventor or joint inventor should further note that the aforementioned functional limitation and/or physicochemical property renders the instant invention ambiguous, vague, incoherent, opaque and/or otherwise unclear to the examiner and fails to meet the statutory requirements of 35 U.S.C. § 112(b), since the limitation merely states a functional limitation and/or physicochemical property (i.e. purity) without providing any clarity regarding how the functional limitation and/or physicochemical property is imparted.
Likewise, the inventor or joint inventor should further note that the instantly recited purity functional limitation and/or physicochemical property does not appear to emanate from and/or does not appear to be an inherent or salient property of the instantly recited Larotrectinib sulfate.
Next, the inventor or joint inventor should further note that the examiner is uncertain whether the instantly recited process for preparing Larotrectinib sulfate, requires an additional unrecited component to be admixed therewith, such as a stabilizer or solvent, to impart the purity functional limitation and/or physicochemical property.
Consequently, the inventor or joint inventor should further note that since the instantly recited process for preparing Larotrectinib sulfate incorporates the aforementioned ambiguous, vague, incoherent, opaque and/or otherwise unclear purity functional limitation and/or physicochemical property, the instantly recited process for preparing Larotrectinib sulfate is rendered indefinite under 35 U.S.C. § 112(b), since one of ordinary skill in the art may not reasonably determine the metes and bounds of the instantly recited process for preparing Larotrectinib sulfate, due to an inability to establish the metes and bounds encompassed by the purity functional limitation and/or physicochemical property.
Then, the inventor or joint inventor should further note that [A] claim which omits matter disclosed to be essential to the invention, as described in the specification or in other statements of record, may also be rejected under 35 U.S.C. § 112(a), as not enabling. {See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976); and MPEP § 2164.08(c)}.
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claims 1, 3, 4 and 9 are further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, base, in claim 1, with respect to step (a), is a relative term which renders the claim indefinite. The term, base, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, on page 3, uses open language, such as preferably, to defines the term, base, as an alkaline or alkaline earth hydroxide; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for preparing Larotrectinib sulfate has been rendered indefinite by the use of the term, base, with respect to step (a).
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The examiner is also available on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624