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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/21/2026, has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/07/2026, have been received and entered into the instant application. As reflected by the attached, completed copies of form PTO-1449, the Examiner has considered the cited references to the extent that they comply with the provisions of 37 C.F.R. §1.97, §1.98, and MPEP §609.
Withdrawn Rejections:
The rejection of claims 12, 15, 19-20 and 23 under 35 U.S.C. 102(a)(1) as being anticipated by Chen of record (Biomaterials, 2013) as evidenced by Gulseren of record (Ultrasonics Sonochemistry, 2007), is overcome by the Applicants’ amendments and is hereby withdrawn. For example, claims 12 and 20 have been amended so that the formulation no longer requires ethanol as a water soluble solubilizer.
The rejection of claims 12, 15, 19-20 and 22-23 under 35 U.S.C. 102(a)(1) as being anticipated by Desai002 of record (U.S. For example, claims 12 and 20 have been amended so that the formulation no longer requires ethanol as a water soluble solubilizer.
The rejection of claims 12-14 under 35 U.S.C. 103 as being unpatentable over Desai002 of record, as applied to claim 12 above and in view of Betts of record (U.S. Patent No. 9,408,884), is overcome by the Applicants’ amendments and is hereby withdrawn. For example, claims 12 and 20 have been amended so that the formulation no longer requires ethanol as a water soluble solubilizer.
The rejection of claims 12 and 18 under 35 U.S.C. 103 as being unpatentable over Desai002of record, as applied to claim 12 above and further in view of Meloun of record (FEBS Lett.,1975), is overcome by the Applicants’ amendments and is hereby withdrawn. For example, claims 12 and 20 have been amended so that the formulation no longer requires ethanol as a water soluble solubilizer.
The rejection of claims 12-16, 18-20 and 22-23 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over the claims of U.S. Patent No. 11,826,492 (‘492 patent) in view of: 1) Desai002 of record (U.S. Pub. No. 20050004002); and 2) Betts of record (U.S. Patent No. 9,408,884), is overcome by the Applicants’ amendments and is hereby withdrawn. For example, claims 12 and 20 have been amended so that the formulation no longer requires ethanol as a water soluble solubilizer.
Status of the claims
Claims 12,14, 18-20 and 22 are pending.
Applicant’s arguments, filed 04/24/2026, 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 of rejections and/or objections presently being applied to the instant application.
Applicants’ amendments, filed on 04/24/2026, have each been entered into the record. Applicants have amended claims 12 and 20. Applicants have cancelled claims 13, 15 and 23. Therefore, claims 12,14, 18-20 and 22 are subject of the Office action below.
Claim Rejections - 35 USC § 103
New Grounds of Rejection Necessitated By Applicants’ Amendments
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 12,14, 19-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Chen of record (Biomaterials, 2013) as evidenced by Gulseren of record (Ultrasonics Sonochemistry, 2007), in view of: 1) Betts of record (U.S. Patent No. 9,408,884); and 2) Khattar et al (hereinafter “Khattar”, U.S. Pub. No. 20110301189, published 12/08/2011).
By way of a background, Applicants disclose their invention as drug formulation comprising a first component, a second component and a third component (see, e.g., page 3 of the specification). The specification (see, e.g., page 15), provides a working example of making a formulation comprising dissolving rapamycin (a first component) in ethanol (a second component) and adding the resulting solution to a water-soluble polymer (a third component) dissolved in aqueous solution of physiological saline.
Under the broadest reasonable interpretation (BRI), consistent with the specification, Applicants’ claimed invention is being interpreted as a method for making a drug formulation comprising combining:
a) a first component comprising at least one rapamycin ester compound of formula:
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;
b) a second component comprising a water soluble solubilizer selected from the group consisting of propylene glycol, polyoxyethylene sorbitan, polyethylene glycol 200 (PEG200), PEG300, PEG400 or combination thereof; and
c) a third component comprising a water-soluble polymer selected from a globular serum protein having a molecular weight (mw) of between 65-70 KD,
wherein, the method comprises solubilizing the first component in the second component and adding the resulting solution to a third component dissolved in an aqueous physiological saline solution.
Similar to the Applicants’ invention (see discussions above), Chen (see §s 22 and 24), teaches a method for making a drug formulation comprising adding a solution of rapamycin dissolved in ethanol to bovine serum albumin (BSA, a water-soluble polymer), dissolved in PBS buffer. Chen does not teach a step of forming nanoparticles of rapamycin, ethanol, BSA or combinations thereof.
Gulseren (see page 179), provides evidence that the mw of BSA as 66 KD.
Chen as evidenced by Gulseren differs from the claimed only insofar as Chen as evidenced by Gulseren is not explicit in disclosing: i) a rapamycin ester of the instant claims; and ii) a water-soluble solubilizer of the instant claims.
However, these aspects of the instant claims would have been obvious over Chen as evidenced by Gulseren, because at the time of the instant invention: i) a rapamycin ester of the instant claims was known in the art; and ii) it was known the art that a water-soluble solubilizer of the instant claims can be employed in the solubilization of a rapamycin ester. For example:
i) Betts (see columns 1-2), teaches a rapamycin 40-O-cyclic hydrocarbon ester compound of formular
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wherein R =
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.
ii) Similar to Chen and Betts (see discussions above), Khattar (see ¶ 0028), discloses that a pharmaceutical composition of rapamycin esters can be formulated by dissolving the esters in alcoholic solvents selected from ethanol, propylene glycol and polyethylene glycol (which necessarily encompasses PEG200, PEG300 and PEG400).
Accordingly, at the time of the instant invention, one of ordinary skill in the art would have had a reasonable expectation of success in replacing: i) rapamycin of Chen with a rapamycin ester compound of Betts; and ii) ethanol of Chen with for propylene glycol or a polyethylene glycol (which necessarily encompasses PEG200, PEG300 and PEG400) of Khattar. This is because the Chen and Betts compounds are very similar with respect to their chemical structure, activity, and solubility profiles. Please see MPEP §2143 (I)(B)). Furthermore, the water-soluble solubilizers of Chen and Khattar are functionally equivalent solubilizers.
Therefore, claims 12, 14 and 20 are obvious over Chen as evidenced by Gulseren and in view of Betts and Khattar.
Regarding claim 19, Chen discloses administration by intravenous injection (see page 1126).
Regarding claim 22, it is a standard of practice in the pharmaceutical arts to enclose a kit or a commercial package comprising therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. In re Gulack, 703 F.2d 1381, 1385, 217 USPQ 401, 404 (Fed. Cir. 1983), holds that when "printed matter is not functionally related to the substrate, the printed matter will not distinguish the invention from the prior art in terms of patentability. Please see MPEP 2112.01(III). Therefore, at the time of the instant invention, one skilled in the art would have found it obvious to enclose a kit or a commercial package comprising the invention of Chen as evidenced by Gulseren and in view of Betts and Khattar, in order to arrive at the invention of claim 22.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 12,14, 19-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Desai002 of record (U.S. Pub. No. 20050004002) in view of: 1) Betts of record (U.S. Patent No. 9,408,884); and 2) Khattar et al (hereinafter “Khattar”, U.S. Pub. No. 20110301189, published 12/08/2011).
Similar to the Applicants’ invention (see discussions above), Desai002 provides a method for the making a pharmaceutical formulation by dissolving rapamycin in chloroform/ethanol (i.e., ethanol is a water soluble solubilizer), then adding the solution into an HSA solution (HSA dissolved in Hanks buffer, see ¶ 0156). Solvent was removed under reduced pressure (lyophilization) and the resulting cake was easily reconstituted by addition of sterile water or saline. The particle size after reconstitution was the same as before lyophilization. Please see ¶ 0056, Example 4.
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Desai002 does not teach a step of forming nanoparticles of rapamycin, ethanol, HSA or combinations thereof, in the formulation before lyophilization and in the formulation after lyophilization.
Desai002 differs from the claimed only insofar as Desai002 is not explicit in disclosing: i) a rapamycin ester of the instant claims; and ii) a water-soluble solubilizer of the instant claims.
However, these aspects of the instant claims would have been obvious over Desai002, because at the time of the instant invention: i) a rapamycin ester of the instant claims was known in the art; and ii) it was known the art that a water-soluble solubilizer of the instant claims can be employed in the solubilization of a rapamycin ester. For example:
i) Betts (see columns 1-2), teaches a rapamycin 40-O-cyclic hydrocarbon ester compound of formular
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wherein R =
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.
ii) Similar to Desai002 and Betts (see discussions above), Khattar (see ¶ 0028), discloses that a pharmaceutical composition of rapamycin esters can be formulated by dissolving the esters in alcoholic solvents selected from ethanol, propylene glycol and polyethylene glycol (which necessarily encompasses PEG200, PEG300 and PEG400).
Accordingly, at the time of the instant invention, one of ordinary skill in the art would have had a reasonable expectation of success in replacing: i) rapamycin of Desai002 with a rapamycin ester compound of Betts; and ii) ethanol of Desai002 with for propylene glycol or a polyethylene glycol (which necessarily encompasses PEG200, PEG300 and PEG400) of Khattar. This is because the Desai002 and Betts compounds are very similar with respect to their chemical structure, activity, and solubility profiles. Please see MPEP §2143 (I)(B)). Furthermore, the water-soluble solubilizers of Desai002 and Khattar are functionally equivalent solubilizers.
Therefore, claims 12, 14 and 20 are obvious over Desai002 in view of Betts and Khattar.
Regarding claim 19 Desai002 discloses that formulations suitable for parenteral administration include aqueous injection solution (see ¶ 0028).
Regarding claim 22, Desai discloses that the formulations can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials (see ¶ 0028).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 12 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Desai002 of record (U.S. Pub. No. 20050004002) in view of: 1) Betts of record (U.S. Patent No. 9,408,884); and 2) Khattar (U.S. Pub. No. 20110301189, published 12/08/2011), as applied to claim 12 above and further in view of Meloun of record (FEBS Lett.,1975).
The limitations of claim 12, as well as the corresponding teachings of Desai002, Betts and Khattar are described above, and hereby incorporated into the instant rejections.
The invention of claim 18 is similar to claim 12, however, claim 18 differs slightly from claim 12 in that claim 18 requires that the global serum protein is a human serum protein having at least 90% homology to SEQ ID NO:1.
Desai002, Betts and Khattar differ from claim 18 only insofar as the cited reference is not explicit in teaching the limitation of claim 18.
However, a person skilled in the art would have had a reasonable expectation of success in arriving at the invention of claim 18, because at the time of the instant invention, a human serum protein having at least 90% homology to SEQ ID NO:1, was known in the art. For example, Meloun teaches the complete amino acid sequence of human serum albumin (see Figure 2, page 136). When this sequence was aligned with SEQ ID NO:1, there was a 99.9% match.
See below sequence comparison:
Database (Db): Prior art sequence
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931
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Query (Qy): Instant SEQ ID NO:1
Therefore, although Desai002 does not teach the sequence of HSA, it would have been obvious to one of ordinary skill in the art to look to the art for any known sequence of HSA. In this regard, Meloun teaches the sequence of HSA with >99% homology to SEQ ID NO:1. Thus it would have been obvious to use a known sequence of HSA with a reasonably predictable result. Since all the elements were known in the prior art, it would have been obvious to combine the known elements to arrive at the instantly claimed invention with no change in their respective functions (see MPEP §2143 (I)(A)).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Non-Statutory Obviousness-Type Double Patenting
New Grounds of Rejection Necessitated By Applicants’ Amendments
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim 12,14, 18-20 and 22 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over the claims of U.S. Patent No. 11,826,492 (‘492 patent) in view of: 1) Desai002 of record (U.S. Pub. No. 20050004002); 2) Betts of record (U.S. Patent No. 9,408,884); 3) Khattar (U.S. Pub. No. 20110301189) and 4) Meloun of record (FEBS Lett.,1975).
The corresponding teachings of Desai002, Betts, Khattar and Meloun are described above, and hereby incorporated into the instant rejections
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent and the instant application are similarly drawn to a composition comprising a macrocyclic triene compound and HAS. For example, the claims of the instant application (e.g., claim 1), are drawn to a method for making a composition comprising a first component comprising at least one macrocyclic triene compound; a second component comprising at least one water soluble solubilizer; and a third component comprising a globular serum protein having an approximate molecular weight of between 65-70 KD, wherein, the method comprises solubilizing the first component in the second component and adding the resulting solution to a third component dissolved in an aqueous physiological saline solution, whereas, the claims of ‘492 patent (e.g., claims 1 and 3-6), are drawn to a composition comprising: i) at least one macrocyclic triene compound; ii) at least one fatty alcohol (a water soluble solubilizer); and iii) a globular serum protein having an approximate molecular weight of between 65-70 KD. Similar to instant claims, a composition of ‘492 patent do not contain nanoparticles of the components or combinations thereof.
Although the ‘492 application is not explicit in claiming: i) a second component of the claimed invention; and ii) a third component dissolved in an aqueous physiological saline solution, the selection of i) a second component of the claimed invention; and ii) a third component dissolved in an aqueous physiological saline solution from the ‘492 application embodiment, would have been obvious in view of Desai002, Betts, Khattar and Meloun.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference patent subject matter.
Conclusions
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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