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 .
Applicants' arguments, filed June 30, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
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.
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.
Claim(s) 14 – 16, 20, 23 - 25, 27 – 29 and 31 were rejected under 35 U.S.C. 103 as being unpatentable over El Sayed et al. (US 2011/0136880) and Zhang et al. (Int J Nanomed, 2013) in view of Velluto et al. (Mol Pharm, 2008) and Reddy et al. (J Cont Rel, 2005). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed January 30, 2026 and those set forth herein.
Applicants traverse this rejection on the grounds that a primary reference must have a reason or motivation to select a specific starting point. Nothing in the instant claims suggests a need for treating cancer, and El Sayed is silent about an endocytosis inhibitor being loaded in to nanoparticles, there is nothing in the reference or provided by the Examiner to construe anything in El Sayed as being consistent with an endocytosis inhibitor, and the reference is completely silent about MPS (mononuclear phagocyte systems) cells or reduced uptake of other nanoparticles by such cells that is the core of the present invention. All claim limitations must be taught or suggested when the references are combined. Art relating to the MPS uptake problem must first be identified by the Examiner and search for the specific concepts of the claims that relate back to the MPS uptake problem. As El Sayed is silent about anything related to MPS, a person of ordinary skill in the art would not have reason or motivation to select El Sayed as a starting point for treating cancer according to the Examiner’s rationale as opposed to reference discussing the nanoparticle uptake problem and the selection of El Sayed is based purely on hindsight using the teachings in specification to reject that claims as obvious and is therefore improper.
These arguments are unpersuasive. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant (see MPEP 2144(IV)). The question is whether one of ordinary skill would have been motivated to subcutaneously administer to a subject two different populations of nanoparticles as set forth in the instant claims. The subject of the instant method is not limited and encompasses patients with cancer. While the ingredients of the nanoparticles in instant claim 1 are defined by function (endocytosis inhibitor, therapeutic agent and diagnostic payload), the patentability of the claims rests with what materials fall within the scope of each term and identical functional labeling in the prior art is not required. Instant claim 31 specifically says “wherein the endocytosis inhibitor is latrunculin A or latrunculin B”, indicating that subcutaneously administered PEG-b-PPS (poly(ethylene glycol)-block-poly(propylene sulfide) nanoparticles comprising latrunculin falls within the scope of the claims. That El Sayed does not specifically call out this function does not the instant claims patentable. The body of the claim recites a complete invention so the preamble does not breathe life into the body of the claim. The wherein clause at the end of claims relating to the MPS system merely reflects the outcome when the subcutaneus administration active steps are carried out. "A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.") MPEP 2111.04 The wherein clause merely characterizes the results of those steps. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicants reiterate that none of the cited references make any mention of MPS cells let alone the reduced uptake of another nanoparticle composition by such cells. All claim limitations must be considered and a searching comparison of the claimed inventions and all its limitations with the prior art must be carried out. The search notes show that no such search was carried out so it is not a surprise that the rejection does not include any mention of MPS cells or the interaction of such cells with nanoparticles.
These arguments are unpersuasive. Attention is directed to MPEP 904 for more information on search requirements during the examination process. Each of three distinct steps set forth have been fully considered by the examiner. There is no proscription that the exact language of the claims be searched, and while all claim limitations must be considered, there is no requirement of literal or explicit teachings in the prior art used to reject the claims and/or that the search must include such terminology identically as set forth in the claims, particularly when the breadth of the claim, and what is or is not included within the scope of the claims is analyzed to inform the search strategy and the weight given the wherein clause in claims 14 is considered.
Applicants argue that the deficiency of the search discussed above is reflected in the rationale as to why nevertheless that claims being obvious that essentially asserts this effect in inherently disclosed in the combination of references and Applicants strongly disagree. As the cited references make no mention of MPS cells so obviousness cannot be predicated on what is unknown. There is a high bar for inherency. A person guided by rationale intent on treating cancer rather than reducing nanoparticle uptake by MPS would not necessarily practice the claimed method steps with the same composition in a manner guaranteeing that the claimed functional limitations would be met. In the absence of any such recognition or suggestion, a person of ordinary skill in the art would not recognize that the missing descriptive matter is necessarily present and that subcutaneous administration of the claimed first population of nanoparticles would necessarily, not maybe or possibly, reduce uptake of the claimed effector nanoparticles when compared to a condition in which the first population was not administered. Even if one accepts that the latrunculin A of El Sayed can act as an endocytosis inhibitor under certain concentrations for treating cancer, this does not mean it must act that way within the complex biological environment in which two materially different nanoparticle populations are administered for the claimed effect on MPS cels. Apart from Reddy, no references are directed to in vivo administration for the treatment of cancer or context for one of ordinary skill in the art to appreciate the effects on MPS cells. The dose of a nanoparticle effective to kill a tumor cell is not necessarily the same dose required to inhibit a macrophage. El Sayed does not teach administration of both populations of nanoparticles and as described in the specification, administration timing greatly affected if the claimed reduced uptake occurred with a 24 hour time frame indicated in the cited section from the specification reproduced in the remarks. It is the Examiner’s burden to address these distinctions and present evidence that the cancer-treatment doses overlap with the functional threshold required for MPS inhibition sinch cancer treatment doses are likely to encompass sub-threshold administration doses high enough to treat cancer but too low to affect the MPS. The wrong standard has been applied by the Examiner and is a clear example of improper burden shifting.
These arguments are unpersuasive. The active steps of the instant claims are rendered obvious by the combined teachings of the applied prior art so arguments that one reference does not explicitly, implicitly, or inherently teach all elements of the claims are not persuasive. When both populations of nanoparticles are administered to the same subject, the same effects must necessarily occur even if those effects are not explicitly described in the applied prior art. A proper finding of inherency does not require that all limitations are taught in a single reference, and the inherency condition may be met with a missing claim limitation when the limitation is “the natural result of the combination of prior art elements.” (MPEP 2112(IV)). Here there is motivation, albeit different from that of Applicants, that renders obvious the administration of both nanoparticles comprising latrunculin A and nanoparticles comprising the therapeutic agent sorafenib to the same subject. As detailed in section V of MPEP 2112, once reasoning to show inherency has been presented with a teaching appearing to be substantially identical, the burden is shifted to Applicants. The comments about the effects of what are effective dosages for treating cancer and alteration of nanoparticle uptake are not supported by evidence. It would have been obvious to optimize the dose of the latrunculin A containing nanoparticles for the treatment of cancer and there is currently no evidence of record that doses effective for the treatment of cancer do not also result inhibition of endocytosis and the effects recited in the wherein clause. Arguments without factual support are mere allegations and are not found persuasive. “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” MPEP 2113 There are no limitations in the instant claims on the timing and co-administration of the two nanoparticles would fall within the 24 hour window from the cited section of the specification. In vivo experiments are not required to establish a prima facie case of obviousness and not a narrow window of concurrent administration or that the latrunculin A or other endocytosis inhibitor containing nanoparticle be administered before the effector nanoparticles comprising the therapeutic agent or diagnostic payload. Only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness. In vitro experiments are very commonly used in the laboratory and the absence of in vivo experiments in the applied prior art alone does not result in one of ordinary skill in the art not having the required reasonable expectation of success.
Applicants argue that Reddy does not cure the inherency problem as this reference also is silent as to reducing MPS cell uptake of the effector nanoparticles and use materially different nanoparticle compositions. The citation indicating that for at least some nanoparticles subcutaneous administration can result in higher tumor uptake and prolonged tumor therapy due to administration at administration site casts further doubt on the inevitable effect of meeting the claimed functional limitations required for inherency. It is impermissible within the framework of section 103 to pick and choose from any one reference only so much of it as will support a given position to the exclusion of other parts. The tumor cells in Reddy were also administered subcutaneously, raising further doubts and weakening the Examiner’s conclusions.
These arguments are unpersuasive. The applied prior art has been considered as a whole. "The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference .... Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 413,425 (CCPA 1981) MPEP 2145(III) The statements highlighted relate to the effects on cancer treatment, which as stated repeatedly by Applicant is not the claimed effect, but one of ordinary skill in the art, given the teaches of all the applied prior art references as to possible administration routes, would have a reasonable expectation of success to administer both populations of nanoparticles to a subject subcutaneously for the treatment of cancer, which is the obviousness rejection of record. The evidence of record has not demonstrated that one of ordinary skill in the art would not have had a reason expectation of success in subcutaneously administering latrunculin A containing nanoparticles and sorafenib containing nanoparticles to a subject for the treatment of cancer would not result in treatment of the cancer. Those are the active steps of the instant claims and the evidence of record does not establish that there would be absolutely no decrease in effector nanoparticle uptake under those conditions as the claims do not specify any particular amount of change in uptake, only reduced uptake.
Applicants also argue that only hindsight is used to combine El Sayed and Zhang, with the secondary references failing to cure the deficiencies of El Sayed. The Examiner has not provided a sufficiently reasoned legal basis for selecting Zhang other than that Zhang discloses a second composition useful for the same general goal of the treatment of cancer. The cancers in the working and prophetic examples of El Sayed do not overlap with the single type of cancer disclosed by Zhang. No compelling reason to select Zhang in combination with El Sayed has been set forth and there is a vast, virtually unlimited array of choices to consider. The selection of Zhang constitutes clear evidence that Applicant’s application has been used as roadmap to selectively pick these two references and is consistent with improper hindsight bias because one of ordinary skill in the art had no knowledge that would have led to the specific selection of these references.
These arguments are unpersuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The quoted section from the prior Office Action omits the remainder of the paragraph that contains with elaboration on the statements quoted that include reasoned legal basis of In re Kerkhoven for the combination of these two references. The fact that it would have been equally obvious to combine other anti-cancer agent containing nanoparticles with latrunculin A does not make the use of a combination of latrunculin A and sorafenib any less obvious. The prior art is presumed to be enabled (MPEP 2121(I)) and it is improper to only look at the examples as prior art is relevant for all that is taught and the teachings are not just limited to the examples. No analysis using the Wands factors has been carried out to demonstrate that the disclosure of El Sayed, which general teaches treating cancers (e.g., abstract and claims 27 – 29), is not enabled. One of ordinary skill in the art would have a reasonable expectation of success that the combination of latrunculin A for the treatment of cancer and the sorafenib containing compositions of Zhang et al. could be combined to form a composition that is also useful for the treatment of cancer.
Regarding Velluto, Applicants argue that the sufficiently required reasoned basis has not been provided. Inasmuch as the rejection is predicated on the general goal of treating cancer, there are a huge number of drug delivery options that differ in their material composition and functional properties. The Examiner must further explain why a PHOSITA would have been motivated to replace the drug delivery system of Zhang with that of Velluto and exclude the countless number of other options similarly disclosed in the prior art. Solubility is not mentioned as a problem with latrunculin A and El Sayed is silent as to delivery agent. Zhang highlights several attractive features of the PEG-PCL co-polymer micelle system. No attempt was made to consider the extent to which the positive properties of Velluto were absent or present properties in the PEG-PCL micelles or vice versa. The rejection has biased its motivation in [a] one-way fashion without consideration of the other options of drug delivery systems. It is impermissible within the framework of section 103 to pick and choose from any one reference only so much of it as will support a given position to the exclusion of other parts. Improper hindsight is again alleged.
These arguments are unpersuasive. There are numerous drug delivery systems known to those of ordinary skill in the art, each with various advantages and disadvantages. That other drug delivery systems could have been selected does not establish the non-obviousness of the particularly claimed combination. Solubility is not the only advantages discussed by Velluto et al. for the use PEG-PPS block copolymers to form drug delivery systems and there is no evidence of unexpected results arising from the use of this material as the drug delivery system.
Claim(s) 29 and 30 were rejected under 35 U.S.C. 103 as being unpatentable over El Sayed et al., Zhang et al., Velluto et al. and Reddy et al. as applied to claims 14 – 16, 20, 23 - 25, 27 – 29 and 31 above, and further in view of Allen et al. (ACS Appl Mater Interfaces, 2018). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed January 30, 2026 and those set forth herein.
No specific arguments regarding Allen were presented for the Examiner to address herein.
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 Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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