DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed September 18, 2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claim 2 is cancelled.
Claims 21-30 are withdrawn.
Claims 1 and 3 – 20 are examined here-in.
Claim Objections
Claim 6 is objected to because of the following informalities:
There is a typographical error in line 2 of claim 6; “amount” should be “about”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6 and 13 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites “wherein the weight-, number-, or volume-based mean diameter of the cores is between about 1 µm and about 50 µm” which does not further limit the recitation of “particles of a weight-, number-, or volume-based mean diameter of the cores is between about 1 µm and about 50 µm…”
Claim 13 recites “wherein the thickness of the overcoating layer is no more than about 1/1000 of the weight-, number-, or volume-based mean diameter of the core, including any discrete layers of coating material” which does not further limit the recitation of “wherein the thickness of the outer overcoating layer is no more than about 1/1000 of the weight-, number-, or volume-based mean diameter of the core, including any discrete layers of coating material.”
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
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 non-obviousness.
Claims 1 and 3 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Carlsson (US 2016/0081945 A1, of record).
Carlsson teaches nanoparticles with solid cores of a biologically active substance with multiple layers of coatings and a diameter range of 1 nm to 50 µm (abstract, paragraphs 0028, 0029, 0070). Carlsson teaches that the thickness of each layer can be varied and controlled down to a monolayer of atoms, resulting in controlled release of a drug (paragraph 0010). Further, Carlsson teaches that the inorganic coating layers can have a thickness ranging from 0.5 to 10 nm (paragraph 0080).
Table 1 below summarizes the relevant examples from Carlsson which show particles with a solid core of a biologically active substances coated with multiple layers of a metal oxide material (paragraphs 0157-0171).
Table 1. Summary of examples from Carlsson
Biologically active core
Additional coating layers
Coating layer material
Final particle size
Example 5
¶ 0157-0160
Felodipine 150 nm
4
Aluminum oxide
160-170 nm
Example 6
¶ 0161-0164
Paracetamol 30 µm
5
Aluminum oxide
30.01-30.02 µm
Example 8
¶ 0171
Felodipine 40 µm
8
Aluminum oxide
40.015 µm
Carlsson teaches that any disruptions in the coating layer, such as holes, can be eliminated by disaggregating the particles via agitation in between applications of the coating layer (paragraph 0025). Carlsson teaches that with alternated agitation and surface coating, the particles can be coated with non-interrupted coating layers (paragraph 0027).
Carlsson teaches that the biologically active substance may include a suitable carrier, such as sugar, lactose, pectin, dextrin, or starch, among others (paragraph 0132).
Claims 1 and 3 – 20 are rendered prima facie obvious over the teachings of Carlsson, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., particles with solid cores and multiple discrete layers of coating) were known in the prior art (e.g., drug delivery) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results (e.g., particles with solid cores and multiple discrete layers of coating for drug delivery) to one of ordinary skill in the art which is prima facie obvious according to MPEP 2143(i)(a).
Carlsson’s teaching for particles with solid cores of a biologically active substance with multiple layers of coatings and a diameter range of 1 nm to 50 µm (abstract, paragraphs 0028, 0029, 0070) reads on instant claim 1. A person of ordinary skill in the art would be motivated to have an outer coating layer that is thinner than any one of the previously-applied layers by Carlsson’s teaching that the thickness of each layer can be varied and controlled in order to modulate the release of drug (paragraph 0010). As an example, a person of ordinary skill in the art would recognize that an outermost layer that is thinner would dissolve more quickly than an outermost layer that is thicker, and therefore would be motivated to choose a thickness for the outermost layer that is appropriate for the desired drug release profile.
Further, Carlsson’s teachings for a particle with a diameter range of 1 nm to 50 µm (abstract, paragraphs 0028, 0029, 0070) wherein the inorganic coating layers can have a thickness ranging from 0.5 to 10 nm (paragraph 0080) reads on the requirement for the outer overcoating layer to have a thickness that is no more than 1/1000 of the diameter of the core. For instance, a particle with a core of 10 µm and an outer layer of 10 nm has meets the recitation for an outer overcoating layer that is no more than 1/1000 of the diameter of the core, reading on instant claim 1.
Carlsson’s teaching that the biologically substance may include a suitable carrier, such as a sugar (paragraph 0132), reads on claim 3 of the instant application.
Carlsson’s example 5 reads on claims 4, 5, and 20 of the instant application which recite the core is a biologically active agent, such as an anti-hypertensive, for use in medicine because example 5’s core is felodipine which is a biologically active anti-hypertensive agent (paragraph 0157).
Carlsson’s teachings for a particle with a diameter range of 1 nm to 50 µm (abstract, paragraphs 0028, 0029, 0070) overlaps on the claimed range of 1 to 50 µm as recited in claim 6 of the instant application. Claimed ranges that overlap with teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Carlsson’s example 6 reports applying discrete layers of coating material to the core sequentially (paragraphs 0161-0164) reading on claim 7 of the instant application which recites “more than one discrete layer of coating material is applied to the core sequentially”.
Carlsson’s example 6 teaches 5 total coating layers (paragraphs 0161-0164), reading on claim 8 of the instant application which recites between 3 and 10 discrete layers of coating material are applied.
Claim 9 of the instant application recites the total thickness of the discrete layers of coating (not including the overcoating layer) is between 0.5 nm and 2 µm. The coating layers in Carlsson’s example 6 are between 10 and 20 nm total (paragraphs 0161-0164) which overlaps on the claimed range of 0.5 nm and 2 µm recited in instant claim 9.
Carlsson teaches that the thickness of each layer can be varied and controlled down to a monolayer of atoms, resulting in controlled release of a drug (paragraph 0010). Further, Carlsson teaches that the inorganic coating layers can have a thickness ranging from 0.5 to 10 nm (paragraph 0080). Instant claim 10 recites the maximum thickness of an individual discrete layer of coating is about 1 hundredth of the diameter of the core. Carlsson’s teaching that the inorganic coating layers can have a thickness ranging from 0.5 to 10 nm (paragraph 0080) in combination with the teaching that the total particle size can range from 1 nm to 50 µm (paragraph 0070) reads on claim 10. For example, an outer coating thickness of 0.5 nm is 1 hundredth of a particle diameter of 50 nm, which is within the particle size range taught by Carlsson (paragraph 0070), therefore reading on instant claim 10.
Carlsson’s teachings that the thickness of each layer can have a thickness ranging from 0.5 to 10 nm (paragraph 0080) also reads on claim 11 of the instant application, because a person of ordinary skill in the art would have the ability to apply a final overcoating layer that is no more than a factor of about 0.7 of the thickness of the widest previously-applied discrete coating. For example, with the teachings of Carlsson that each discrete layer can have a thickness ranging from 0.5 to 10 nm (paragraph 0080), a person of ordinary skill in the art could apply a coating layer of 1 nm followed by a final overcoating layer of 0.7 nm, thus meeting instant claim 11’s recitation that the final overcoating layer that is no more than a factor of about 0.7 of the thickness of the widest previously-applied discrete coating.
Carlsson’s teaching that the inorganic coating layers can have a thickness ranging from 0.5 to 10 nm (paragraph 0080) in combination with the teaching that the total particle size can range from 1 nm to 50 µm (paragraph 0070) also reads on claim 12 of the instant application because an overcoating layer thickness of 0.5 to 10 nm (paragraph 0080) overlaps with the claimed range of 0.3 to 10 nm and the total particle size range of 1 to 50 µm (paragraph 0070) overlaps with a claimed particle size of up to 20 µm.
In Carlsson’s examples 6 and 8 the cores are 30 µm and 40 µm, respectively (paragraphs 0161-0164, 0171). Carlsson teaches that the additional layers of coating are 10-20 nm and 15 nm (paragraphs 0161-0164, 0171). The thickness of the outermost overcoating layer is therefore necessarily less than 10-20 nm and 15 nm. For example 6, an outermost layer less than 10-20 nm is less than 0.03-0.06% of the 30 µm core, which overlaps on the claimed “no more than about 1/1000” (which would be no more than 0.1%) as recited in claim 13. For example 8, an outermost layer less than 15 nm is also less than 0.03% of the 40 µm core, overlapping on the claimed “no more than about 1/1000 of the weight-, number-, or volume-based mean diameter of the core, including any discrete layers of coating material” as recited in instant claim 13.
Carlsson specifically discloses that the particles in each example do not have contact holes (paragraphs 0160, 0164, ). Particles with no contact holes read on claim 14 of the instant application, which recites the particles are essentially free of abrasions, pinholes, breaks, gaps, cracks, and/or voids.
The particles in Carlsson’s examples 5, 6, and 8 are coated with aluminum oxide (paragraphs 0157 – 1064, 0171). Aluminum oxide is an inorganic compound, thus reading on claim 15 of the instant application which recites the coating materials comprise one or more inorganic materials. Aluminum oxide is a metal oxide compound, reading on claims 16-19 of the instant application.
Double Patenting
The judicially created doctrine for non-statutory double patenting rejections has been described in detail in the previous action.
Double Patenting over 18/568,363
Claims 1-5 and 15 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1 and 4-9 of copending Application No. 18/568,363 in view of Carlsson (as cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because: instant claim 1 is drawn to a composition with a plurality of particles that have a mean diameter between 1 and 50 µm where the particles have a solid core and multiple discrete layers of coating material with the outermost layer of coating material is thinner than the other layers.
Conflicting claim 1 is drawn to a pharmaceutical formulation with a plurality of particles that have a mean diameter between 10 nm and 700 µm where the particles have a solid core comprising a biologically active drug and an inorganic coating.
The instant and conflicting claims differ because conflicting claim 1 recites the solid core is a biologically active drug, the coating is inorganic, and the concentration of biologic active drug is at least 50 mg/mL. The instant claim also recites the outermost layer of coating material is thinner than the other layers, which the conflicting claim does not specify.
However, Carlsson teaches nanoparticles with solid cores of a biologically active substance and multiple layers of coatings (abstract, paragraphs 0028, 0029, 0070) and teaches that the thickness of each layer can be varied and controlled down to a monolayer of atoms, resulting in controlled release of a drug (paragraph 0010).
It would be prima facie obvious to apply the teachings of Carlsson to conflicting claim 1 for an outermost coating layer that is thinner than the other layers to arrive at instant claim 1. A person of ordinary skill in the art would have been motivated to apply the teachings of Carlsson to control the thickness of each layer because Carlsson teaches the layer thickness modulates release of a drug (paragraph 0010). Therefore, with the teachings of Carlsson, claim 1 of the conflicting application is prima facie obvious according to MPEP 2143(i)(a) as combining prior art elements according to known methods to yield predictable results.
Conflicting claim 1’s requirement for solid core to be a biologically active drug in conflicting claim 1 reads on claims 2-5 of the instant application.
Conflicting claim 1’s requirement for the coating to be an inorganic material in conflicting claim 1 reads on claim 15 of the instant application which recites the coating is an inorganic material.
Conflicting claim 4 recites the biologically active drug is an immunoglobulin, a monoclonal antibody, an antibody mimetic, a cytokine, or a cytokine receptor antagonist or agonist, reading on claim 5 of the instant application.
Conflicting claim 5 recites the biologically active drug is an immunoglobulin, reading on claim 5 of the instant application.
Conflicting claim 6 recites the biologically active drug is a monoclonal antibody, reading on claim 5 of the instant application.
Conflicting claim 7 recites the biologically active drug is an antibody mimetic, reading on claim 5 of the instant application.
Conflicting claim 8 recites the biologically active drug is a human peptide hormone, reading on claim 5 of the instant application.
Conflicting claim 9 recites the biologically active drug is a cytokine or cytokine agonist, reading on claim 5 of the instant application.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Examiner’s Reply to Attorney Arguments Dated September 18, 2025
Applicant argues that the instantly claimed particles were previously misunderstood by the Examiner and that the particles have an outer overcoating layer with a thickness that is less than the thickness of any one of the previously-applied layers (Remarks page 9). Applicant argues that Carlsson does not disclose or suggest that the particles have a thinner outer overcoating layer (Remarks page 10). The Examiner disagrees, because as discussed in the body of the rejection above, Carlsson’s teachings for a particle with a diameter range of 1 nm to 50 µm (abstract, paragraphs 0028, 0029, 0070) wherein the inorganic coating layers can have a thickness ranging from 0.5 to 10 nm (paragraph 0080) reads on the requirement for the outer overcoating layer to have a thickness that is no more than 1/1000 of the diameter of the core. For instance, a particle with a core of 10 µm and an outer layer of 10 nm has meets the recitation for an outer overcoating layer that is no more than 1/1000 of the diameter of the core, reading on instant the instant claims.
Applicant argues that it would not have been obvious “to prepare particles with a thinner overcoating layer since there is nothing in Carlsson that suggests any advantage provided by a thinner overcoating layer” (Remarks page 10). The Examiner disagrees because, as discussed in the body of the rejection above, a person of ordinary skill in the art would be motivated to have an outer coating layer that is thinner than any one of the previously-applied layers by Carlsson’s teaching that the thickness of each layer can be varied and controlled in order to modulate the release of drug (paragraph 0010). As an example, a person of ordinary skill in the art would recognize that an outermost layer that is thinner would dissolve more quickly than an outermost layer that is thicker, and therefore would be motivated to choose a thickness for the outermost layer that is appropriate for the desired drug release profile.
Applicant appears to allege unexpected results, stating that “this date demonstrates that particles with a thinner, outer overcoating layer have a superior coating integrity and reduced initial burst release of active ingredient compared to particles without a thinner, outer overcoating layer” and “Carlsson provides no expectation that the claimed invention would result in particles having an improved coating integrity and a reduced burst release of active ingredient” (Remarks page 11).
As an initial matter, the Examiner notes that a proper side-by-side comparison to the closest prior art as required by MPEP 716.02(e) does not appear to have been made. Applicant compares particles with a core size of 5.9 um then four additional subshells of 4 – 5 nm each with particles having a core size of 5.9 um, four additional subshells of 4 – 5 nm each, and one “sealing shell” of an estimated 3 nm (instant specification example 1, figures 3 and 4). Applicant alleges that a sealing shell thinner than any of the previously applied layers results in “particles having an improved coating integrity and reduced burst release of active ingredient”. The Examiner disagrees that the comparison is proper because it appears that the particles with four subshells were resuspended then monitored for drug release in figure 3, then dried, then coated with a 3 nm “sealing shell” (Example 1 specification page 28 lines 24 – 34, Example 9 page 34 lines 27 – 36). As such, it seems that the particles were allowed to release drug, then were coated with a “sealing shell”, then resuspended and measured for drug release again. Therefore, the second instance of drug release had less drug to release than the previous instance – thereby confounding the “cause” of slower drug release.
Furthermore, assuming purely arguendo that a proper side-by-side comparison was made, even then the Examiner would be skeptical as to the supposed “thinner” outer “sealing shell” resulting in slower release because 1) with the current experimental narrative it appears the previous subshells were at least somewhat degraded by the initial resuspension and drug release measurement, 2) the “thinner” thickness of the “sealing shell” is estimated and the total particle diameter is the same as without the sealing shell, and 3) it is unclear if the amount of drug available for release at time zero in Figure 3 is the same amount of drug available for release at time zero in Figure 4. Applicant has not fully explained the significance of the data in arriving at the conclusion that results are unexpected as required by MPEP 716.01©(II) and 716.02(b)(II). As such, it is not clear to the Examiner how Applicant’s argument is supported by the proffered evidence.
Finally, and purely arguendo, even if Applicant has in fact shown unexpected results (of which the Examiner is not persuaded at this time), the Examiner notes that Applicant’s alleged showing is in regards to the release profile of the drug from a composition which does not appear to be “reasonably representative” of the claims in their current scope. See MPEP 716.02(d). The Applicant has allegedly demonstrated improved coating integrity and reduced burst release of ingredient for 5.9 um diameter indomethacin cores with 4 aluminum oxide shells of 4 – 5 nm each and one aluminum oxide “sealing shell” of 3 nm, however if this is in fact true it would only have been shown for a specific combination of biological active agent, 4 discrete layers of one coating material, and a final overcoating layer (Examples 1 – 8 each have the same particle composition, Example 9 has a different particle composition). It is unclear that a composition containing the specific combination of biological active agent and layers would be reasonably representative of compositions containing other biological active agents (such as those listed in claim 5) and/or other layer compositions or number of layers, thereby falling within the broader scope of what is presently claimed.
Applicant argues that the provisional non-statutory double patenting rejection should be withdrawn because Carlsson does not sufficiently suggest that the outer overcoating layer should be thinner than the previous layers (Remarks page 12). The Examiner disagrees, because as discussed in the body of the rejection above, Carlsson teaches nanoparticles with solid cores of a biologically active substance and multiple layers of coatings (abstract, paragraphs 0028, 0029, 0070) and teaches that the thickness of each layer can be varied and controlled down to a monolayer of atoms, resulting in controlled release of a drug (paragraph 0010). A person of ordinary skill in the art would have been motivated to apply the teachings of Carlsson to control the thickness of each layer because Carlsson teaches the layer thickness modulates release of a drug (paragraph 0010). Furthermore, a person of ordinary skill in the art would recognize that an outermost layer that is thinner would dissolve more quickly than an outermost layer that is thicker, and therefore would be motivated to choose a thickness for the outermost layer that is appropriate for the desired drug release profile. Therefore, with the teachings of Carlsson, claim 1 of the conflicting application is prima facie obvious according to MPEP 2143(i)(a) as combining prior art elements according to known methods to yield predictable results. The provisional non-statutory double patenting rejection is maintained.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Toriana N. Vigil whose telephone number is (571)270-7549. The examiner can normally be reached Monday - Friday 9:00 a.m. - 5:00 p.m. EST.
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/TORIANA N. VIGIL/Examiner, Art Unit 1612
/FREDERICK F KRASS/Supervisory Patent Examiner, Art Unit 1612