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
The remarks of 16 September 2025 are entered.
Claims 1-6, 8-9, and 13-30 have been canceled. Claims 7, 10-12, and 31-33 are pending. Claims 10-12 and 31 are withdrawn with traverse. Claims 7, 32, and 33 are being examined on the merits.
The election requirement remains in effect.
The rejection of claims 7 and 32-33 under 35 U.S.C. 103 as being unpatentable over ‘322 and ‘286 in view of ‘731 is maintained, with the Examiner’s response found below.
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 (i.e., changing from AIA to pre-AIA ) 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, 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 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.
Claims 7 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Schluesener et al. (WO 2006/114322 A1, published 2 November 2006, hereafter referred to as ‘322) and Deretic et al. (WO 2016/138286 A1, published 1 September 2006, hereafter referred to as ‘286) in view of Mayell F (WO 2017/070731 A1, published 4 May 2017, hereafter referred to as ‘731).
All functional limitations of claims 7, 32, and 33 are being interpreted as natural physiological effects of administration of the elected species: MDP.
The ‘322 art discloses treatment of Alzheimer’s disease (AD) by administration of a composition comprising a NOD2 agonist, specifically muramyl dipeptide (MDP, also known as N-acetylmuramyl-L-alanyl-D-isoglutamine, see e.g. claims 1, 3, 6, and 7; [0053]; [0055], STIC machine translation).
The ‘286 application discloses treatment of AD by administration of a NOD2 agonist comprising MDP (see e.g. Abstract; p. 1, par 3; p. 46, 3rd full par., 1st sentence; claims 1- 2, and 17- 18). The ‘286 application also discloses treatment protocols according to the disease to be treated (see e.g. p.46, 3rd full paragraph, 1st sentence).
The difference between the ‘322 and ‘286 art and the claimed invention is that the specific treatment protocol of 1-4 days per week for at least 3 months of instant claim 7 is not taught by ‘322 or ‘286.
The ‘731 art discloses that AD is characterized by accumulation of extracellular β-amyloid plaques in the brain (see e.g. [0007]). The ‘731 art also discloses the use of crosslinked MDP to treat the symptoms of AD (see e.g. [0011]-[0012]). The administration is disclosed as being once a week and such that the appropriate dosage, total amount administered, and duration can be optimized as needed by a medical practitioner based upon the subject to be treated, including increasing or decreasing timing (see e.g. [0036]). A specific example shows administration of the crosslinked MDP over a period of at least 3 months (see e.g. Example 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the NOD2-agonist based AD treatment of ‘322 and ‘286 by administering to a subject in need a therapeutically effective amount of muramyl dipeptide, and in doing so utilize the treatment rationale of ‘731 concerning crosslinked MDP and weekly or greater dosing for a period of at least 3 months to arrive at the claimed invention. The rationale comes from the common treatment of AD with MDP as evidenced by ‘322 and ‘286 and the ‘731 showing a highly related crosslinked MDP was known to be administered at least weekly and demonstrated to be administered over a period of years. There would have been a reasonable expectation of success because the skilled artisan was guided by ‘322 and ‘286 for treatment of AD and merely had to optimize dosing timing and duration through routine experimentation, both of which were supported by the protocol of ‘731. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Moreover, the dosing of an active agent is clearly a result effective variable that must be determined based on a variety of factors including the age, body weight, and health of the patient, the condition to be treated and severity, the route of administration, the particular drug used, adverse drug effects or toxicity, clinical response to treatment, etc., and is routinely optimized by the skilled artisan (e.g., this is one of the main factors tested in clinical trials 1, 2A, and 2B). Applicant is advised that recitation of dosages/regimens, without more, is generally insufficient to patentably distinguish over the prior art.
Further, the current record does not support a finding that the claimed dosing protocols are critical. “The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range.” In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990). See MPEP § 716.02 - § 716.02(g). To establish unexpected results over a claimed range, Applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960).
With respect to claims 32 and 33, the functional limitations are rejected because, a chemical composition and its properties are inseparable. Thus, if the prior art teaches the identical chemical structure, the properties Applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. See also MPEP § 2111.04(I), which states that a whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. Additionally, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Response to Arguments:
The Applicants summarize the rejection of record.
The Examiner finds no issues with the summary as provided.
The Applicants argue the Examiner cites ‘731 to overcome the deficiency in the treatment protocol despite it teaching away from administration of MDP and only teaches administration of MIS6 microparticles.
The Examiner disagrees that ‘731 teaches away from the base ‘322 and ‘286 art. While it does utilize crosslinked MDP, the base MDP is still present and offers a reasonable linkage to the treatment of Alzheimer’s in both ‘322 and ‘286 via administration of MDP. Again, in this case the skilled artisan is only utilizing a different treatment protocol from ‘731, well within the level of ordinary skill in the art.
The Applicants argue ‘731 disclose a crosslinked MDP but does not recognize the glycopeptide form of MDP for controlling monocytes and reducing Aβ. The Applicants argue ‘731 does not disclose administering MDP in a dose that increases the patrolling monocytes as claimed.
The Examiner argues that the glycopeptide form of MDP is provided by ‘322 and ‘286. The ‘731 art merely provides a rationale for a different treatment protocol. The dose is provided by ‘322 and ‘286, and as previously discussed the fact that Applicants have recognized another advantage (increase in patrolling monocytes) that would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences are otherwise obvious.
The Applicants argue the formulation in ‘731 is a complex of microparticles formed by combination of bacterial membrane extracts with ligands of TLR9. The Applicants argue this is different from the claimed MDP which they argue is not associated with any other contaminants. The Applicants argue the ‘731 composition has bacterial membrane fragments. The Applicants argue ‘731 describes MDP as having significant toxicity in vivo as compared to the instant invention showing beneficial effects of MDP on patrolling monocytes. The Applicants argue ‘731 focuses on reducing MDP toxicity and thus teaches away from the instant invention.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The ‘322 and ‘286 art provides for use of a base MDP to treat Alzheimer’s disease and reduce Aβ. Furthermore, given the “comprising” transitional phrase of the instant claims nothing precludes inclusion of additional elements. While ‘731 may utilize alternative methods to reduce in vivo toxicity, the use of MDP as the base at least leads one of ordinary skill in the art to a reasonable linkage to ‘322 and ‘286 in order to achieve the claimed treatment protocol.
The Applicants’ arguments have been considered but are not persuasive. The rejection is maintained.
Conclusion
No claims are allowed.
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.
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/Z.J.M/Patent Examiner, Art Unit 1658 /SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658