DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election with traverse of Group V in the reply filed on 12/08/2025 is acknowledged. Applicant argues that, “when citing lack of unity of invention in a national stage application, the Examiner has the burden of explaining why each group lacks unity with each other group specifically describing special technical features in each group” (Applicant Arguments, Page 3).
Applicant is directed to Paragraph 3 of the Requirement for Restriction mailed on 10/07/2025, which states the following:
“The inventions listed as Groups I-V do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
The technical feature of Groups I-III is a pulverulent, diastereomerically pure DL/LD-methionylmethionine, whereas the technical feature of Group V is DL/LD-methionine diketopiperazine. As such, Groups I-III do not share a special technical feature with the instant claims of Groups IV-V. Therefore, the claims are not so linked within the meaning of PCT Rule 13.2 so as to form a single inventive concept, and unity between Groups I-V is broken.”
As discussed by MPEP 1850, “[l]ack of unity of invention may be directly evident “a priori,” i.e., before considering the claims in relation to any prior art... For example, independent claims to A + X, A + Y, X + Y can be said to lack unity a priori as there is no subject matter common to all claims”
As clearly articulated in the Requirement for Restriction, there is no technical feature, special or otherwise, shared between all Groups of Invention.
Applicant next argues that “a search of all the claims would not impose a serious burden on the Office” (Applicant Arguments, Page 4).
The argument is not found persuasive. The instant Application is a 371 of PCT/AU2020/050742. As discussed by MPEP 823, “[t]he analysis used to determine whether the Office may require restriction differs in national stage applications submitted under 35 U.S.C. 371”. Significantly, that analysis does not include search burden.
For the same reasons, Applicant’s arguments based on MPEP 806.03 (Applicant Arguments, Page 4) are not found persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election with traverse of a single method in the reply filed on 12/08/2025 is also acknowledged.
The elected species read upon claims 1-6.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kobler et al (CA 2740663 (2010)).
Claim 1 is drawn to a method for the preparation of DL/LD-methionine diketopiperazine having the following formula (I):
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the method comprising:
Reacting a DD/LL-methionylmethionine-containing aqueous solution or suspension having a pH of 4 to 7 measured using a pH electrode at 20oC at a temperature of 150 to 200oC until an aqueous solution or suspension has formed containing at least a proportion of 30 mol% DL/LD-methionine diketopiperazine, based on the total content of DL/LD- and DD/LL-methionine diketopiperazine in the reaction mixture.
Kobler et al teach “DD/LL-methionylmethionine (DD/LL-I) were dissolved together with... KHCO3 in 75 ml of water in a 200 ml Roth laboratory reactor and heated to 160oC while stirring... and, after 6 hours at this temperature, the autoclave was cooled in an ice bath” resulting in a suspension from which bis[2-(methylthio)ethyl]-2,5-piperazinedione (III) was isolated having a “diastereomer ratio: 54:46 (DD/LL-III : meso-III)” (Page 45, Lines 25-31, Example 21).
However, as evidenced by the instant Specification (Pages 12-13, Example 12), the pH of the above process taught by Kobler et al is 9.1 as opposed to 4-7.
Yet, as further taught by Kobler et al, the process can “take place with a base and for a pH of from 7.5 to 14” (Page 22, Lines 4-5).
As discussed by MPEP 2144.05, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists” (citing In re Wertheim, 541 F.2d 257 (CCPA 1976); In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465 (Fed. Cir. 1997)). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (citing Titanium Metals Corp. of America v. Banner, 778 F.2d 775 (Fed. Cir. 1985)).
In the instant case, the instantly claimed pH range of 4 to 7 is considered prima facie obvious over the prior art pH range of 7.5 to 14.
As such, claim 1 is rejected as prima facie obvious.
Claims 2-3 are drawn to the process of claim 1, wherein the aqueous solution or suspension has a pH of 4 to 6 (claim 2) and/or wherein the reacting is at a temperature of 175 to 210oC (claim 3).
As stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454 (CCPA): “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the pH and reaction temperature in a process are clearly a result effective parameter. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal pH and temperature in order to best achieve the desired results.
As such, claims 2-3 are also rejected as prima facie obvious.
Claim 4 is drawn to the process of claim 1, wherein the total concentration of DL/LD- and DD/LL-methionylmethionine equivalents in the form of DL/LD- and DD/LL-methionine diketopiperazine in the reaction mixture at the end of the reaction is in the range from 0.1% to 18% by weight.
Applicant is reminded that the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When, as here, the prior art appears to contain the exact same elements as those instantly claimed, the burden is properly shifted to Applicant to show otherwise. As stated in In re Best, Bolton, and Shaw, “Where… the claimed and prior art products are... produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product" 562 F2d 1252 (CCPA 1977). In the instant case, the claimed and prior art process is substantially identical. As such, absent evidence to the contrary, it is asserted that carrying out the prima facie process of Kobler et al would result in the total concentration of DL/LD- and DD/LL-methionylmethionine equivalents in the form of DL/LD- and DD/LL-methionine diketopiperazine in the reaction mixture at the end of the reaction in the range from 0.1% to 18% by weight. See also In re Fitzgerald 619 F2d 67 (CCPA 1980): the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on.”
As such, claim 4 is also rejected as prima facie obvious.
Claims 5-6 are drawn to the process of claim 1, wherein a DD/LL-methionylmethionine-containing aqueous solution or suspension is used which already contains DL/LD-methionylmethionine (claim 5), more specifically up to a proportion of 30 mol% of DL/LD-methionylmethionine based on its total content of DD/LL- and DL/LD-methionylmethionine (claim 6).
Kobler et al teach, in Example 12, racemization of either DL/LD-methionylmethionine (Page 45, Lines 1-24) or racemization of DD/LL-methionylmethionine (Page 45, Lines 1-24, Example 12) to yield DD/LL/DL/LD-mthionylmethionine (I).
Accordingly, it would have been obvious to use either, or both, in the process of Kobler et al.
And, in doing so, it would have been prima facie obvious to determine the amount of each of said DL/LD-methionylmethionine and DD/LL-methionylmethionine to use therein. As stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454 (CCPA): “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the concentration of starting ingredients in a process utilizing said ingredients is clearly a result effective parameter. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal amount of each of said DL/LD-methionylmethionine and DD/LL-methionylmethionine in order to best achieve the desired results.
As such, claims 5-6 are also rejected as prima facie obvious.
Allowable Subject Matter
The proposed claims would be ALLOWABLE:
A process for the preparation of DL/LD-methionine diketopiperazine represented by formula (I):
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(I),
the process comprising:
reacting a DD/LL-methionylmethionine-containing aqueous solution or suspension at a temperature of 150 to 200oC for 30 to 120 minutes to form an aqueous solution or suspension containing at least 60 mol% of DL/LD-methionine diketopiperazine based on the total content of DL/LD- and DD/LL-methionine diketopiperazine in the reaction mixture;
wherein the DD/LL-methionylmethionine-containing aqueous solution or suspension has a pH of 4 to 7 as measured using a pH electrode at 20oC.
The process according to Claim 1, wherein the DD/LL-methionylmethionine-containing aqueous solution or suspension has a pH of 4 to 6 as measured using a pH electrode at 20oC.
The process according to Claim 1, wherein the reacting is at a temperatulre of 175 to 210oC.
The process according to Claim 1, wherein the total concentration of DL/LD- and DD/LL-methionylmethionine equivalents in the form of DL/LD- and DD/LL-methionine diketopiperazine in the reaction mixture at the end of the reaction is in the range from 0.1% to 18% by weight.
The process according to Claim 1, wherein the DD/LL-methionylmethionine-containing aqueous solution or suspension further comprises DL/LD-methionylmethionine.
The process according to Claim 5, wherein the proportion of DL/LD-methionylmethionine in the DD/LL-methionylmethionine-containing aqueous solution or suspension is up to 30 mol% based on the total content of DD/LL- and DL/LD-methionylmethionine.
As discussed above, the instantly claimed method is prima facie obvious over Kobler et al (CA 2740663 (2010)) which teach related methods of making DD/LL-methionine diketopiperazine differing in the pH of the process, wherein it would have been obvious to modify the pH in said process. Yet, as demonstrated by Applicant, modifying the pH in the process of Kobler et al unexpectedly provides higher yields of DD/LL-methionine diketopiperazine (at least 60 mol%) without byproduct formation, after a one-hour reaction time.
The proposed claims would be ALLOWABLE over Kobler et al because the proposed process is drafted commensurate in scope with the unexpected results.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET. 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, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611