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 .
Priority
The present Application, filed August 16, 2024, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/US2023/062760, filed February 16, 2023, which claims priority to U.S. Provisional Patent Application Nos. 63/479,333, 63/329,595, and 63/311,698, filed January 10, 2023, April 11, 2022, and February 18, 2022, respectively.
Status of the Claims
In the amendment filed August 16, 2024, claims 1-33 are canceled and new claims 34-53 are added. Claims 34-53 are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 24, 2026 is acknowledged.
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 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 34-35 and 37-53 are obvious over Toler:
Claims 34-35 and 37-53 are rejected under 35 U.S.C. § 103 as being unpatentable over U.S. Patent Application Publication No. 2020/0308144 by Toler et al. (hereinafter, “Toler”).
Claim 34 recites a pharmaceutical composition, comprising a compound of Formula A, or a pharmaceutically acceptable salt thereof:
PNG
media_image1.png
190
355
media_image1.png
Greyscale
and an oil component.
Toler discloses multimeric compounds of Formula I (Abstract)
PNG
media_image2.png
291
301
media_image2.png
Greyscale
where the variable groups are as defined. Toler further discusses rimiducid
PNG
media_image3.png
231
451
media_image3.png
Greyscale
,
a previously known compound that would otherwise fall within the scope of Toler Formula I, but is expressly disclaimed (paragraph [0023]). It will be noted that rimiducid is the compound of instant Formula A, except that instant Formula A does not specify the two stereocenters that are specified in rimiducid. As such, the rimiducid of Toler is an example of a compound of instant Formula A. As such, the rimiducid of Toler, having partially specified stereochemistry, is an example of a compound of instant Formula A having unspecified stereochemistry.
Toler further teaches that the rimiducid-adjacent multimeric compounds of Formula I can be formulated in the same or a similar formulation as for rimiducid (paragraph [0311]), and that pharmaceutical compositions of such multimeric compounds may be formulated with a solvent or diluent that can include “water, saline, dextrose, ethanol, glycerol, oil, and the like,” (emphasis added) and can include an excipient or carrier with examples such as polyethylene glycol, polysorbate, ethanol, glycerol, and “an oil, such as a vegetable oil” (paragraph [0294]; see also paragraph [0299], disclosing a liquid carrier comprising, among other things, vegetable oils).
It would have been obvious to apply the teachings of Toler regarding formulated pharmaceutical compositions of the disclosed multimeric compounds to the rimiducid, as Toler expressly states. As such it would have been obvious, in view of the express teachings of Toler, to prepare a pharmaceutical composition having rimiducid (i.e., instant compound A) along with an oil as a solvent or diluent and/or an oil, such as a vegetable oil as an excipient or carrier (i.e., an oil component). As such, application of the formulation teachings of Toler to rimiducid renders claim 34 obvious over Toler.
With respect to claim 35, Toler discloses oil in general as a suitable solvent for the rimiducid composition. The three oils of instant claim 35 are within the scope of the “oil” of Toler, and are obvious variations of said “oil,” particularly where, as here there is no showing of any particular functional distinction of or advantage to the recited oils. Selection of a specific, conventional oil from within this genus, absent any showing of a functional distinction between the selected oil and other members of the disclosed genus, would have been an obvious matter of routine formulation choice to a person of ordinary skill in the art.
With respect to claims 37-38, Toler teaches the pharmaceutical composition can include an excipient or carrier chosen from a group that includes polysorbate (paragraph [0294]). With respect to claim 39, polysorbate 80 is within the scope of the general polysorbate of Toler r, and absent any showing of functional distinction or advantage, polysorbate 80 is merely one of several obvious species selections within the genus of Toler’s polysorbate. Claims 40-41 combine the features of claims 35 and 38 and are therefore obvious for the same reasons as are claims 35 and 38.
With respect to claims 42-43, Toler teaches the pharmaceutical composition can include solvents such as water and/or ethanol in combination with oil (paragraph [0294]). With respect to claim 44, Toler teaches that fatty acids may be employed as excipients together with a liquid carrier, disclosing thickeners such as “fatty acids, fatty acid salts and esters, fatty alcohols” (paragraph [0327]). It would have been obvious to include such a fatty acid as part of or in addition to the oil component of the composition. With respect to claim 45, similar to the analysis of claims 35 and 39, selection of a C8 fatty acid is merely an obvious example within the broader disclosure of a fatty acid of Toler, when there is no showing of any functional distinction or advantage to the C8 fatty acid.
Claim 46 combines the features of claims 41 and 44 and is therefore obvious for the same reasons as are claims 41 and 44. With respect to claim 47, the rimiducid of Toler is the compound of instant Formula B.
With respect to claim 48, the limitation “for administration by injection, subcutaneous administration, and/or intramuscular administration” is directed to an intended use of the claimed composition and does not further limit the structure of the composition. As such, it is accorded no patentable weight. See Minton v. Nat’l Ass’n of Sec. Dealers, 336 F.3d 1373 (Fed. Cir. 2003); MPEP § 2111.04. It is further noted that Toler discloses pharmaceutical forms suitable for injectable use (paragraph [0321]), satisfying this limitation even if given patentable weight.
Similarly, with respect to claim 49, the limitation “for multimerization of a fusion protein and/or for eliminating cells containing a fusion protein, wherein the fusion protein comprises a polypeptide that binds to the compound of Formula A, or the pharmaceutically acceptable salt thereof,” is directed to an intended use of the claimed composition and recites a fusion protein that is not itself a positively recited component of the claimed composition. As such, it is accorded no patentable weight. It is further noted that Toler discloses the use of rimiducid to crosslink chimeric polypeptides containing a multimerizing region, and that contacting cells expressing such chimeric polypeptides together with an apoptosis-inducing polypeptide with rimiducid activates a cellular safety switch, resulting in apoptosis (paragraph [0036]), satisfying this limitation even if given patentable weight.
Claim 50 recites a method comprising combining a compound of Formula A with an oil component to provide a pharmaceutical composition for injection and/or topical administration. As described above with respect to claim 34, the composition itself is obvious over Toler – the feature that the composition is “for injection and/or topical administration” is an intended use of the composition that is not afforded patentable weight. The composition itself is a combination of components, and the method of making it that generically involves combining the constituent components is obvious over the composition itself. Stated alternatively, because Toler teaches the combination of a multimeric compound like rimiducid with an oil, the act of combining rimiducid with an oil is likewise obvious over Toler.
Claim 51, is essentially identical to claim 34, except that it specifies rimiducid rather than a compound of Formula A (which is rimiducid but with stereochemistry unspecified). Claim 51 is therefore obvious for the same reasons as is claim 34. Claims 52-53, which depend from claim 51 and recite features that encompass those of claims 41 and 46, respectively, are thus obvious for the same reasons as applied above to claims 41 and 46.
Claim 36 is obvious over Toler and Foreman:
Claim 36 is rejected under 35 U.S.C. § 103 as being unpatentable over Toler, in view of U.S. Patent No. 10,413,508 to Foreman et al. (hereinafter, “Foreman”).
Claim 36 recites the pharmaceutical composition of claim 34, wherein the oil component is about 5% to about 50% by volume in the pharmaceutical composition (or is about 25% to about 35% by volume in the pharmaceutical composition).
Toler is applied to claim 36 as to claim 34, above, but does not expressly teach any particular percent composition of oil in the pharmaceutical composition. It would have been obvious to utilize an oil percentage within a range of from about 5-50%, however, because oil percentages within this range were known in the art to be useful for solubilizing hydrophobic active pharmaceutical ingredients in emulsion-based pharmaceutical compositions. See, for example, Foreman.
Foreman teaches a method of preparing an oil-in-water emulsion for preparing medicines that deliver a substantially water insoluble active pharmaceutical ingredient (Abstract; col. 1, lines 6-10), and teaches the method is applicable to APIs such as rapamycin and tacrolimus (col. 4, lines 31-39), APIs that are similarly hydrophobic to, and share a similar pipecolic acid ester pharmacophore to that of rimiducid. Foreman teaches the method includes mixing an aqueous phase comprising non-ionic surfactant, polyol, and water with an oil phase, where the weight ratio of the oil phase to the aqueous phase is between about 0.01:1 and 1:1 (col. 2, line 65 through col. 3, line 16). This weight percentage of about 1% to about 50% oil to aqueous by weight broadly overlaps with the presently recited v/v range of about 5-50%. It would have been obvious, when utilizing a solvent of combined oil and water, with an excipient such as polysorbate for a multimeric compound pharmaceutical composition of Toler, to prepare the composition as a stable emulsion of the type disclosed by Foreman, utilizing a weight ratio of about 1-50% (w/w) oil to aqueous phase as further taught by Foreman, for stable delivery of the hydrophobic API, rimiducid.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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 S Lundgren can be reached on (571) 272-5541. 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.
/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
Prosecution Insights