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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 29, 2025 has been entered.
Response to Arguments
Applicants' arguments, filed December 29, 2025, 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.
Regarding the previously applied Masuda et al. (WO 2017/204209) reference, Applicants cites ¶¶ [0039] and [0040] of this reference in their entirety that discusses the content of inorganic nanoparticles in the composite particles that are higher than the claimed range of 1% - 9.6% by mass. The claimed macrophage imaging agent exhibits excellent effects such that macrophages existing in a living body can be easily observed by using the imaging agent with NMR as the macrophage imaging agents integrates macrophages in a human body. The particles of Masuda have a ligand and there is no concept that the particles could be used as a macrophage imaging agent with a gadolinium oxide content of 1 – 9.6% by mass as Masuda clearly requires 80% by mass of greater of the inorganic nanoparticle.
These arguments are unpersuasive. Given the amendments to claim 1, claim 1 is no longer rejected over Masuda et al. alone. However, ¶ [0039] of Masuda states “according to one embodiment of the present invention” which does not mean that this limitation applies to all embodiments. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). (MPEP 2123). Furthermore, “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). MPEP 2123, emphasis added. The teachings of the new Wang et al. reference that are discussed below renders obvious optimization of the coating thickness, that will in turn alter the mass percent of gadolinium oxide present in the composite particles. There is no evidence of record as to the criticality of the claimed range. The presence of a ligand is not excluded from the products of the instant claims. The instant claims are drawn to a product and as such, the recitation “macrophage imaging agent for magnetic resonance imaging (MRI)” reflects the intended use of the claimed product. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim and a product as recited in the claims is disclosed by the prior art as discussed in greater detail below. Explicit appreciation of the claimed intended use in the applied prior art is not required to anticipate or render obvious the claimed subject matter.
Election/Restrictions
Newly submitted claim 5 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: claim 5 is drawn to a method of using the claimed particles, but the scope of the particles does not match the scope of the products of claim 1 which were elected in the Response to Restriction/Election Requirement filed January 21, 2025 as no amount of gadolinium oxide is required in claim 5. The common element of the particles of claim 1 and claim 5 does not represent a special technical feature as it does not make a contribution of the prior art including Masuda et al. (WO 2017/204209) whose teachings are discussed in detail below.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 5 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Specification
The disclosure is objected to because of the following informalities: different trade names are given the same generic terminology (e.g., TRITON® X-100 and X-114) and no evidence or explanation has been provided to indicate that the generic terminology added for each trademark or trade name reflects the particular material or product covered by the trademark or trade name as of the time of filing as a trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name
Appropriate correction is required.
It is also noted that while the paragraph numbers given in the amendments to the specification filed July 11, 2025 and December 29, 2025 align with the specification as originally file, the citations by page and line number only align for the amendment to the figure description in the July 11, 2025 specification amendment. Improper location information for amendments to specification could cause confusion and the possibility of the mailing of a Notice of Non-Compliant Amendment.
Claim Interpretation
Claim 4 is a Jepson claim. In such a claim, there is an implied admission that the subject matter of the preamble is the prior art of another as there is no credible reason of record for drafting in Jepson format given to overcome that presumption.
Claim Rejections - 35 USC § 112 – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 1 has been amended to recite that the content of gadolinium oxide in the composite particle, which comprises a gadolinium oxide containing particle, ranges from 1% to 9.6% by mass. This range is not supported by the disclosure as originally filed. 9.6% gadolinium oxide content for the composite particles was determined for the material prepared in Example 1 (beginning at ¶ [0115], ¶ [0120] in particular). However, no other values for the gadolinium oxide in the composite particle is present in the disclosure as originally filed. ¶ [0094] states that content of the gadolinium oxide- containing particles (emphasis added) cannot be absolutely determined because the content differs depending on the uses of the macrophage imaging agent and the like but nevertheless states that the content of the gadolinium oxide-containing particles (emphasis added) is preferably 1% by mass or more with additional ranges for the lower threshold (¶ [0094] and ¶ [0083] of the specification as originally filed cited by Applicant). However, claim 1 is not limiting the content of the gadolinium oxide- containing particles but the gadolinium oxide portion of the particles so such values are not relevant the newly added claim limitation. Therefore claim 1 contains new matter.
If Applicant is in disagreement with the Examiner regarding support for the amended claim, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention.
Claim 4 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
For a Jepson claim, the invention is not only the claimed improvement recited after the preamble of such a claim but the totality of what is set out in the claim and the totality must have written description support in the disclosure as originally filed (In re Xencor, Inc., No. 24-1870 (Fed. Cir. Mar. 13, 2025)).
The preamble of claim 4 recites “a composite particle comprising a gadolinium oxide-containing particle and a coating film positioned on a surface of the gadolinium oxide-containing particle. The full breadth of such particles is not supported by the disclosure as filed as the broadest disclosures that could be located was “a cover film that contains a polymer obtained by polymerizing a monomer component containing a monomer having an ethylenically unsaturated bond” (abstract) and “composite particles each including an organic polymer and inorganic nanoparticles” (¶ [0011]). The preamble encompasses particles with inorganic or organic coatings and therefore is broader than the subject matter encompassed by the preamble.
There is also not clear support in the disclosure as originally filed for the improvement of “providing visualizable images” set forth as part of the improvements over the prior art and no citations were provided that were relevant to this claim limitation.
If Applicant is in disagreement with the Examiner regarding support for the new claim, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention.
Claim Rejections - 35 USC § 112 – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims that recite method step(s) of using the apparatus are indefinite (see MPEP 2173.05(p)(II)). Writing the claim in Jepson format does not permit the presence of an active method step in a claim drawn to a composition and “providing visualizing images” is a method step.
That method step is also unclear as “providing” and “visualizing” are both verbs but there is no word such as “and” between the two verbs. Must images be both provided and visualized? Or does this step merely require providing visual images?
The scope of the improvements required by the Jepson claim are also unclear. While the claim does end with a period, the claims are currently presented sets forth just two separate limitations – the aforementioned “providing visualizing images” and the composition of the coating film. However, the word “and” does not precede the second limitation but rather appears to be the second item in a list of at least three items since given the lack of a word such as “and” or “or” and the comma before the second limitation relating to the composition of the coating film. Is there at least one additional improvement that has been omitted for the Jepson claim or was a word such as “and” omitted from the complete list two improvement limitations?
Please clarify.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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 4 is rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as being unpatentable over Masuda et al. (WO 2017/204209; all citations from US 2020/0319171, the PGPub of the national stage entry). This rejection is MAINTAINED for the reasons set forth herein.
Masuda et al. discloses composite particles including an organic polymer and inorganic nanoparticles (e.g., ¶ [0011]). Coated particles comprising a composite particle such as that according to ¶ [0011] and a polymer layer coating the composite particles (¶ [0024]) are disclosed. Among the discloses inorganic nanoparticle are gadolinium and oxides thereof (¶ [0061] and claim 7). The particle size of the inorganic particles contained in the composite particles is preferably from 2 – 25 nm (¶ [0064]). The content of the inorganic nanoparticles in the coated particles is preferably from 1 - 95% by mass (¶ [0139]). The content of the styrene is preferably 60 – 100% mass with the narrowest most preferable range being 80 – 90% by mass with respect to 100% of the mass of the total amount of the organic polymer contained in the composition particles. The organic polymer can also contain a crosslinkable monomer (¶¶ [0053] – [0054]) and in one embodiment, the content of the organic polymer in the composite particles is not particularly limited (¶ [0060). In example 1, the particles were coated using a mixture of styrene and divinylbenzene (¶ [0173]) while in example 2, the particles were coated with a mixture of methyl methacrylate and trimethylolpropane trimethacrylate (¶ [0175]). In Example 1 (¶ [0173]), the coating was prepared using the radical initiator 2,2’-azobisisobutyronitrile (omitted from the mass calculations of the final polymer coating composition) in the presence of 1.35 g (90% by mass) styrene, a monomer having a carbon-carbon double bond, and 0.15 g (10% by mass) of divinylbenzene, a divinyl crosslinking monomer.
There is no explicit disclosure of a gadolinium oxide particle coated with a polymer such as those used in examples 1 and 2 of Masuda et al. and the amount of gadolinium oxide required of claim 1.
Where selection of one named species from a list of alternatives is all that is required to arrive at the instantly claimed subject matter, that species is anticipated. Ex Parte A., 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). See also In re Sivaramakrishnan, 213 USPQ 441 (CCPA 1982). But if the coating of gadolinium oxide particles is not anticipated by Masuda et al. the use of an oxide of gadolinium is rendered obvious from the disclosure of oxides of materials such as gadolinium and the knowledge of one of ordinary skill in the art as to the ability of metals such as gadolinium to form oxides. It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to select a metal oxide from the list of suitable inorganic nanoparticles disclosed by Masuda et al. and to apply the organic polymer layer such as those used in the examples resulting in product of claim 4. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because such materials are disclosed by Masuda et al. and it is well within the skill of one of ordinary skill to select from options that are disclosed in the prior art.
The use of the disclosed materials for imaging is not disclosed. As the instant claims are drawn to a product, this is the intended use of the claimed material. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. This is further bolstered by the recitation of “capable of producing imaging information relating to macrophages in living bodies” being recited in the preamble of the Jepson claim.
Claim Rejections - 35 USC § 103
Claim(s) 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Masuda et al. (WO 2017/204209; all citations from US 2020/0319171, the PGPub of the national stage entry) in view of Wang et al. (Nanotechnology, 2016).
Masuda et al. is discussed above.
Explicit motivation to vary the amount of coating material, that will also affect the mass percent of the gadolinium oxide in the composite particle is not disclosed.
Wang et al. discloses while gadolinium oxide (Gd2O3) is the most promising magnetic resonance imaging (MRI) positive contrast agent due to its high paramagnetism and good biocompatibility, post surface modification is necessary to convert the particles from hydrophobic to hydrophilic (p 2, col 1, ¶ 2). Total longitudinal relaxation is influenced by the surface paramagnetic Gd3+ ions and distance between the water proton and paramagnetic centers (that is the thickness of a modification coating layer; p 2, col 1, ¶ 2). Polymer shell thickness can be adjusted by varying the synthesis parameters (p 2, col 2, ¶ 2). As shown in Figures 4(a) and 4(b), the polymer to Gd2O3 mass ratio alters the average hydrodynamic size of the resultant particles (p 7, col 2, ¶ 2), resulting in three kinds of nanoparticles with different coating thicknesses (p 9, col 1, ¶ 1). Decreased coating thickness decreases the distance between the paramagnetic center and the surrounding water proton, suggesting a thinner polymeric coating is desirable for preparing T1 contrast agents with significantly enhanced relaxtivity to promote interaction between the paramagnetic center and the surrounding water protons (p 9, col 2, ¶ 1). However, the samples with the thinnest polymeric coating exhibited the lowest cellular viability with the thickest coating showing the lowest toxicity (p 10, col 2). Thinner coating enhanced r1 relaxtivity but thicker polymeric layers prevent Gd3+ ion leakage to improve biocompatibility (abstract). Therefore it is important to strike a balance between biocompatibility and the r1 relaxtivity behavior (abstract).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the thickness of the coating of the materials of Masuda et al. to optimize the signal obtained when the contrast agent is used and the biocompatibility and toxicity of the coated particles. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Wang et al. discloses that it is important to strike a balance between biocompatibility and the r1 relaxtivity behavior that are affected in opposite ways by coating thickness. When applied to the same size gadolinium oxide particle, one with a thinner coating will have a higher mass percent of gadolinium oxide compared to one with a thicker coating. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of coating in order to best achieve the desired results. “The 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.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05. There is no evidence of record as to the criticality of the claimed ranges.
Conclusion
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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/Nissa M Westerberg/Primary Examiner, Art Unit 1618