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 .
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 08/03/2026 are acknowledged.
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the previous rejection is maintained and modified to address claim amendments. Please see the examiners response to applicants below.
Response to Arguments
Applicants argue that the Examiner cannot assume that because a compound shows some effect on mouse burrowing behavior, it would necessarily improve specific human cognitive parameters (inhibitory control and impulsivity) as measured by a specific human cognitive assessment (anticue task). This appears to be impermissible hindsight reconstruction using Applicant's own disclosure as a roadmap.
It may be a different methodology to measure the desired parameters. However, the root mechanism is same from the teachings of cited art, which is administration of subtilisin A hydrolysate of lysozyme in both cases.
Applicants argue that in the present application, the inventors "surprisingly found in a randomized double- blind, placebo controlled, cross-over study that administering a composition comprising a protein lysate to human subjects resulted in improved cognitive functioning." See e.g. paragraph [0047] of the present specification. This unexpected result in humans cannot be predicted from Jonker's mouse studies, even if combined with Adam.
It appears that applicants failed to explain why the shown data or unexpected results in humans cannot be predictable. In fact, in the drug discovery, first step is testing the drug in vitro, then in vivo and then in animal models, such as mouse or rat, monkey etc., before testing on humans in clinical trials, which is a common practice in the art.
Applicants argue that the Jonker reference does not teach an effective amount for improving inhibitory control or impulsivity.
The term “effective amount” is a functional limitation, and it refers to a quantity of an active ingredient sufficient to achieve a stated therapeutic or functional effect, but it is not a fixed numerical value unless the disclosure defines it. In this case, example 9 of Jonker, quantity of active ingredients is being administered to get functional tests. This amount is interpreted as an effective amount.
Applicants argue that the claimed "effective amount" is not a result-effective variable that could be optimized through routine experimentation because Jonker provides no starting point or guidance for what amount would be effective for improving inhibitory control or impulsivity in humans Jonker only tested mice for burrowing behavior related to neurodegenerative disease progression.
Jonker recognized the property of subtilisin A hydrolysate of lysozyme and also exemplified with a quantity of active ingredients in example 9. Concentrations of active ingredients depend on the condition(s) of composition or formulation, because of solvent(s) or other components in the composition may alter the property of active agents. So, a skilled person in the art would determine suitable concentration range of active agent through a routine experimentation, until it achieves a recognized results or property.
Claim Rejections - 35 USC § 103
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 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.
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 of this title, 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 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 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, 5, 12-14 and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Jonker (WO 2017/144443 A1) in view of Adam (Acta Psychologica, 2015, 161, 137-144).
For claim 1:
Jonker teaches a functional test on male mice by administering NWT-03 (aka subtilisin A hydrolysate lysozyme) by using burrowing test [see Examples 8 and 9], wherein the test comprising the following:
The mice were habituated to the procedure a week prior to the test by placement of the burrow tube into the home cage. After two baseline measurements the burrow test was performed. The mouse was placed in a cage with the burrow tube containing 200 g of food pellets. The difference between the burrowing behavior at the start (t = 9 weeks) and the end (t = 21 weeks) of the treatment was determined.
It was found that the mice fed with a high fat diet (group 1) and those fed with a high fat diet in combination with NWT-02 burrowed substantially the same amount of material (-2.1 gram and -2.5 gram respectively) at the beginning and the end of the test (figure 1). Mice fed with a high fat diet containing NWT-03 burrowed 12.7 gram on average, whereas the mice fed with a high fat diet comprising both NWT-02 and NWT-03 burrowed 25.2 grams on average.
It is concluded that NWT-03 has a positive effect on cognition and may be used for the treatment of neurodegenerative diseases. This effect is synergistically enhanced by the addition of NWT-02.
In the above NWT-03 is subtilisin A hydrolysate lysozyme [see preparative method in Example 3, wherein Alcalase is also known as subtilisin A]. The high burrowing behavior is nothing but improving cognitive function, specifically improving control of impulsivity and improve inhibitory control etc.
The above disclosure of Jonker is interpreted applicants “method of improving cognitive function in a subject by administering subtilisin A hydrolysate lysozyme”, since results showed improving in the burrowing behavior.
The difference is that Jonker is silent on anticue task in their disclosure.
First, anticue task is a cognitive test or task to measure a specific desired parameter in a subject, and which is known in the art, see below. Second, previously cited prior art teaches same drug, i.e., NWT-03 (aka subtilisin A hydrolysate lysozyme), to a subject to improve cognitive function, as explained above. Finally, if anticue task is applied to the teachings of Jonker, the results should match applicants shown data, since same drug is applied to the subject to improve cognitive functioning.
In addition, Adam teaches anticue test and its advantages measuring improvement in inhibitory control and control of impulsivity [see sections Abstract, General Discussion and Conclusion].
Therefore, one would be motivated to use anticue task in light of its advantages for measuring desired parameters.
For claim 5:
Jonker teaches a male mouse for their in vivo animal experiments [see example 8], wherein mouse before the treatment is interpreted as a healthy subject.
Jonker is silent on healthy human subject. However, the data shown in mouse model can be extended to human subject, which is a known common practice in the art, absent evidence to the contrary.
For claims 12-13:
Jonker teaches that in the preparative example, a maximum molecular weight of less than 10 kDa with the peptide distribution of 46% < 500Da, 23% 500-1000Da, 32% >1000Da. The degree of hydrolysis of 21% [see Example 3].
For claim 14:
It is not clear about daily dose amounts of subtilisin A hydrolysate lysozyme from the disclosure of Jonker. However, these amounts are considered as a result effective variables and so, a skilled person in the art would determine the optimal dose amounts through a routine titration of experimentation.
For claim 16:
Jonker further teaches that their composition comprising subtilisin A hydrolysate lysozyme can be mixed with food stuff [see lines 21-26 in page 5; line 34 in page 7 to line 4 in page 8].
For claim 17:
Jonker is silent on human male subject of at least 60 years old. However, the data shown in mouse model can be extended to human subject in need thereof, which is a known common practice in the art.
For claims 18-19:
It is a test to measure a desired parameter. It may be a different methodology, but the criticality is in the root mechanism for treating the condition, which is administration of subtilisin A hydrolysate of lysozyme, which is obvious over the cited art.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components in the composition and their use in improving cognitive functioning, and known measuring tests for a desired parameters etc, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify or extrapolate the teaching the art to a desired subject can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
