DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22 2025 has been entered.
Receipt of Arguments/Remarks filed on December 22 2025 is acknowledged. Claims 6-10, 12, 14, 17-18, 21-22, 28-32, 34-36 and 40 were/stand cancelled. Claims 1 and 23 were amended. Claims 1-5, 11, 13, 15-16, 19-20, 23-27, 33 and 37-39 are pending. Claims 3, 5, 23-27, 33 and 37-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 25 2025. Claims 1-2, 4, 11, 13, 15-16 and 19-20 are directed to the elected invention.
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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62959077, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The response filed December 22 2025 amended claim 1 to recite an X-ray diffraction to have at least one peak having a signal to noise ratio of greater than 3. This limitation does not find support in the prior filed document. No X-ray diffraction patterns are present nor does any of the documentation recite at least one peak having a signal to noise ratio of greater than 3.
Therefore the effective filing date of claims 1-2, 4, 11, 13, 15-16 and 19-20 is January 7 2021.
Specification/Incorporation by Reference
The attempt to incorporate subject matter into this application by reference Yu et al. (J Pharm Sci 2020 Nov 109(11): 3480-3089) (page 17) is ineffective because it refers to a Non-Patent Literature to incorporate essential subject matter, specifically subject matter required to provide support under 112a written description.
While this portion of the specification clearly provides reference to the root words “incorporate” and “reference” and the reference is clearly identified. The reference is non-patent literature. 37 CFR 1.57(c) make it clear that essential subject matter may be incorporated by reference, but only by way of an incorporation by reference to a US Patent or US Patent application number. Essential material is that which provides written description of the invention.
This section of the instant specification also is not specific with regards to the subject matter to be incorporated. Page 17 recites “in its entirety” which is not sufficient to permit incorporation of material not specifically identified in the incorporation statement. The only specifically identified information is MDM structures.
See MPEP 608.01(p); In re Saunders, 444 F.2d 599, 170, USPTQ 213 (CCPA 1971); Advanced Display Systems, Inc. v. Kent State Univ., 212 F.3d 1272, 54 USPQ2d 1673 (Fed. Cir. 2000).
The incorporation by reference will not be effective until correction is made to comply with 37 CFR 1.57(c), (d), or (e). If the incorporated material is relied upon to meet any outstanding objection, rejection, or other requirement imposed by the Office, the correction must be made within any time period set by the Office for responding to the objection, rejection, or other requirement for the incorporation to be effective. Compliance will not be held in abeyance with respect to responding to the objection, rejection, or other requirement for the incorporation to be effective. In no case may the correction be made later than the close of prosecution as defined in 37 CFR 1.114(b), or abandonment of the application, whichever occurs earlier.
Any correction inserting material by amendment that was previously incorporated by reference must be accompanied by a statement that the material being inserted is the material incorporated by reference and the amendment contains no new matter. 37 CFR 1.57(g).
Claim Rejections - 35 USC § 112-Indefiteness
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.
Claims 1-2, 4, 11, 13, 15-16 and 19-20 are 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.
Claim 1 as amended is vague and indefinite. Claim 1 recites: “wherein the antiviral therapeutic agent nanoparticle powder is a homogeneous powder characterized by powder X-ray diffraction to be free of individual antiviral therapeutic agent signatures, be free of individual antiviral therapeutic agent signatures present in a simple mixture of the individual antiviral therapeutic agents, have at least one peak having a single to noise ratio of greater than 3, and has a cohesive unified X-ray diffraction pattern representing multiple drug domains assembled in repeating units;”. However, the specification does not include any x-ray diffraction patterns nor describe what is meant by a cohesive unified x-ray diffraction pattern representing multiple drug domains assembled in repeating units. The specification (step 1, general procedure for making the aqueous dispersion, page 33) states similar language. This portion of the specification indicates that the MDM (multiple dug domains) can be different from that of amorphous x-ray diffraction presented typically as a broad halo with no single peak in the drug powder products. But still does not indicate what is meant by cohesive unified x-ray diffraction pattern. While the claim was amended, the claim still recites “have at least one peak” which means there can be more peaks than one present. The examiner can find no evidence that this term is a term of the art. No other art discusses cohesive unified x-ray diffraction pattern. Nothing in the instant specification indicates what the x-ray diffraction (i.e. the identification of any peak) associated in the composition such that the metes and bounds of the claim are clearly discernible. As implied by the statement in the claims, the x-ray diffraction pattern would not be the same as the individual therapeutic agent. Therefore, there must be some change in the x-ray diffraction pattern upon forming the composition. But neither the claims nor the specification indicate the boundaries for determining that the x-ray diffraction pattern is free of individual antiviral therapeutic agent signatures. The claim not recites “simple mixture of individual antiviral therapeutic agents” but never indicates what is meant by simple mixture. The specification merely just states that the at least one peak can have a different 2θ peak position than the diffraction peak 2θ positions for a simple physical mixture of the individual components of the antiviral therapeutic agent composition. But never indicates what a simple mixture is such that one can tell the difference between just a “physical mixture” opposed to a “simple mixture”.
The instant specification (page 37) indicates that after solvent removal, the formation of stable DcNP powder could be verifiable by X-ray diffraction pattern of the powder. Instead of formation of halo or broad scan across x-ray angle, which reflect the amorphous powder product or crystalline peaks for each drug in the mixture, the DcNP powder exhibited a unique and unified peak for all drugs in the mixture plus the two lipid excipients. So does that mean that any x-ray diffraction pattern that isn’t a halo or broad scan is sufficient to say the powder x-ray diffraction is free of individual antiviral therapeutic agent signatures and has a cohesive unified x-ray diffraction pattern? The specification never clearly indicates what is the “unique and unified peak”.
Claims 2, 4, 11, 13, 15-16 and 19-20 are included in the rejection as they depend on a rejected base claim and they do not clarify the issues.
Response to Arguments
Applicants’ arguments filed December 22 2025 have been fully considered but they are not persuasive.
Applicants argue that claim 1 has been amended to additionally clarify the structure of the X-ray diffraction pattern. It is argued that this amendment renders the claim definite.
Applicants arguments are not persuasive. Claim 1 as amended recites “at least one peak having a single to noise ratio of greater than 3”, the recitation “at least one” indicates there can be more than one peak. But then the claim also states that the powder has a cohesive unified X-ray diffraction pattern. None of the argument explain what this term means. The application is utilizing this X-ray diffraction pattern in an attempt to distinguish the instant claims from the prior art. However, nothing in the specification or the arguments explains what the X-ray diffraction pattern actually looks like beside there is at least one peak (located anywhere) that has a single to noise ratio of greater than 3. The comparison is to a “simple mixture” but neither the claims, the arguments nor the specification explain what is meant by a “simple mixture”. Thus, neither the amendments nor the arguments have clarified the scope of the claims, specifically the X-ray diffraction pattern.
Claim Rejections - 35 USC § 112-Written Description
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.
Claims 1-2, 4, 11, 13, 15-16 and 19-20 are 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.
Claim 1 recites: “wherein the antiviral therapeutic agent nanoparticle powder is a homogeneous powder characterized by powder X-ray diffraction to be free of individual antiviral therapeutic agent signatures, be free of individual antiviral therapeutic agent signatures present in a simple mixture of the individual antiviral therapeutic agents, have at least one peak having a signal to noise ratio of greater than 3 and have a cohesive unified X-ray diffraction pattern representing multiple drug domains assembled in repeating units;”. However, the instant specification never provides written description on the x-ray diffraction, the structure on how an x-ray diffraction with at least one peak with a signal to noise ratio greater than 3 and what is meant by the recitation free of individual antiviral therapeutic agent signature and a cohesive unified x-ray diffraction pattern representing multiple drug domains assembled in repeating units.
Page 34 of the instant specification shows how powder x-ray diffraction was performed. This section of the specification teaches that: The two lipid excipients- 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[poly (ethylene glycol)2000] (mPEG20oo-DSPE); as well as all the active pharmaceutical ingredients or drugs- Dolutegravir (DTG) , Efavirenz (EFV), Lopinavir (LPV), Ritonavir (RTV), Atazanavir (ATV); Lamivudine (3TC or L), Tenofovir (TFV) and its prodrug Tenofovir disoproxil fumarate (TDF) and Tenofovir alafenamide (TAF), Emtricitabine (FTC)-all exhibited unique identifiable crystalline peak characteristic each on XRD scan profile over the 2-50 degree 2Θ. However, the specification never describes what these unique identifiable crystalline peak characteristics are so that one skilled in the art would readily understand what peaks would need to be absent to fall within the scope of the instant claims.
The instant specification (page 37) indicates that after solvent removal, the formation of stable DcNP powder could be verifiable by X-ray diffraction pattern of the powder. Instead of formation of halo or broad scan across x-ray angle, which reflect the amorphous powder product or crystalline peaks for each drug in the mixture, the dcNP powder exhibited a unique and unified peak for all drugs in the mixture plus the two lipid excipients. No where in the specification is the unique and unified peak for the drugs in the mixture described. Nor does the specification describe where the at least one peak having a signal to noise ratio of greater than 3 is located.
Therefore, the specification establishes that the x-ray diffraction is unique but never identifies what the x-ray diffraction looks like.
MPEP 2163 states that (emphasis added):
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.’" Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612.
As set forth above, the instant specification teaches that the dcNP powder exhibited a unique and unified peak for all drugs in the mixture but the specification never described what is that unique and unified peak.
The state of the art, see Caira for example, teaches that x-ray diffraction is a technique for solid-sate characterization and is able to provide a unique pattern for any given crystallin phase. The pattern generated represents a “fingerprint” of the phase in question (introduction). The x-ray diffraction pattern (PXRD) technique is used extensively in the identification of multi-component compounds and increasingly in the context of the characterization of new pharmaceutically relevant phases that might display advantageous properties, such as enhanced solubility of the active pharmaceutical ingredient (API). Following co-grinding of an equimolar mixture of two components in the presence of chloroform for 10 minutes, the PXRD pattern of the product was recorded; this pattern differs significantly from those of the components, indicating probable formation of a binary compound, a salt or a co-crystal being the most likely products (multi-component compounds). Heating solid APIs, or multi-component compounds containing APIs, generally induces reactions and phase transitions such as loss of solvent of crystallization (for solvated materials), conversion of one polymorphic form to another, transformation of amorphous phases to crystalline phases, fusion and thermal decomposition (variable temperature pxrd).
Therefore, the state of the art establishes that how the composition is made has an effect on the resulting x-ray diffraction pattern and the x-ray diffraction pattern provides a way to identify compounds in a multi-component composition.
Since the specification teaches the x-ray diffraction exhibits a unique and unified peak and Caira recognizes that the ways the components are combined as well as heating can result in differences in the x-ray diffraction pattern, the specification fails to provide written description for the scope of the powder claimed. The response filed August 14 2025 alleges the instantly claimed product possesses an unexpected effect compared to the prior art. The claimed “multiple drug domain” structure as claimed is only ever taught in the art by Applicant. It is this structure and the X-ray diffraction that applicant is utilizing in an attempt to distinguish the instantly claimed structure from the prior art. Therefore, written description support of what the x-ray diffraction as claimed is as well as how it is achieved is required. Nothing in the specification provides any specific description, for example specific intensities, nor does the specification show any x-ray refraction pattern data to allow one skilled in the art to recognize applicants were in possession of the claimed invention.
Response to Arguments
Applicant’s arguments filed December 22 2025 have been fully considered but they are not persuasive.
Applicant argue (page 9) that that the X-ray diffraction pattern is highlighted at paragraph 0076 of the published application. It is argued that this portion of the specification provides a detailed discussion that makes the language in the claims both definite and comply with the written description. This section also incorporates by reference to Yu which illustrates the state of the art in the field.
Regarding Applicant’s arguments, Yu is Applicant’s own work. The only art that refers to multi-drug domains is Applicants own work. Therefore, the reference cannot be said to illustrate the state of the art. Furthermore, the examiner cannot agree that the incorporation is to non-essential subject matter. The MPEP makes it clear that incorporation by reference to material which is required to provide written description support is considered essential material and cannot be made to Non-Patent literature. Furthermore, the instant specification only makes reference to incorporation of multi-drug motifs not the X-ray diffraction patterns. Nothing in the incorporation statement makes it clear that the X-ray diffraction is incorporated by reference only the MDM structure.
Looking to Yu, while there are X-ray diffraction patterns show which recite a single large peak (Figure 1i) which could be said to have a signal to noise ratio of 3 (the reference does not expressly state this but assuming the noise is 1000 and the peak is 3000 this is a ratio of 3). This is for a specific combination of LPV (lopinavir), RTV (ritonavir), TFV (tenofovir) and 2 lipid excipients DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) and DSPE-PEG2000
(1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]). Yu et al. teaches that controlled solvent removal by spray drying is a critical step in locking these constituents together (page 3481, right column, 2nd complete paragraph). Therefore, Yu teaches an x-ray diffraction pattern with a single peak (not at least one as claimed), a ratio of 3 (not greater than 3 as claimed) and for a specific combination of drug (which is not claimed) and a combination of 2 specific lipids (not one or more as claimed). While variant-6 shows that the combination of lamivudine/tenofovir/dolutegravir (reading on (i) in claim 1) forms a multi-drug-motif structure. Nothing in Yu et al. supports that any multi-drug motif necessarily has the x-ray diffraction as claimed. A single x-ray diffraction is not representative of the full scope. Furthermore, Yu et al. suggests the criticality with regards to controlled spray-drying. However, example 1 states that the solvent can be removed by spray drying or lyophilization. Iwamoto et al. (WO2016205384) previously cited claims that the solvent is removed by evaporating, desiccating under reduced pressure, spray drying or a combination thereof (see claim 48). But Applicant argued the results, specifically the plasma half-life, is different for Iwamoto than the instant claims (see remarks filed August 14 2025, pages 11-12). The instant specification does not make clear how a different structure is formed in the instant application from the prior art, especially in light of the same drugs, same lipid excipients and same solvent removal (spray drying) being utilized. The claims include an x-ray diffraction pattern which is not expressly taught by Iwamoto. Nothing in Yu et al. establishes that structural or process of making would necessarily form the x-ray diffraction claimed over the full scope of the claims. Therefore, the examiner cannot agree that paragraph 0076 or the Yu et al. provide the appropriate written description support.
Conclusion
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636