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 .
DETAILED ACTION
Claims 1, 9-11, 19-21, 23-26, 28, 29, 32, 45, 47, 49, 53, 55, 57, 59, 60, 109, 110 and 115 are currently pending in the instant application. Claims 1, 9-11, 19-21, 23-25, 28-29, 32, 57, 59 and 60 are rejected, claims 26, 45, 47, 49, 53 and 55 are objected and claims 109, 110 and 115 are withdrawn from consideration in this Office Action.
I. Priority
The instant application is a 371 of PCT/US2020/046758, filed on August 18, 2020 which claims benefit of US Provisional Application 62/888,959, filed on August 19, 2019.
II. Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 16, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
III. Restriction/Election
A. Election: Applicant's Response
Applicants' election without traverse of Group I in the reply filed on January 16, 2026 is acknowledged.
Subject matter not encompassed by elected Group I are withdrawn from further consideration pursuant to 37 CFR 1.142 (b), as being drawn to nonelected inventions.
B. Status of the Claims
i. Scope of the Search and Examination of Elected Subject Matter
Formulation III comprising crystalline TAF sebacate, micronized, biodegradable polymer (PLGA8515) and an anti-inflammatory agent (methylprednisolone acetate).
The above structure is the provisional elected species.
ii. Extended Prior Art Search M.P.E.P. §803.02
Following election, the Markush-type claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. If the Markush-type claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush-type claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration. On the other hand, should the examiner determine that the elected species is allowable, the examination of the Markush-type claims will be extended. If prior art is then found that anticipates or renders obvious the Markush-type claim with respect to a nonelected species, the Markush-type claim shall be rejected and claims to the non-elected species held withdrawn from further consideration. The prior art search, however, will not be extended unnecessarily to cover all nonelected species.
As indicated above, Examiner searched the compound based on the elected species, above, in response to the requirement to restrict the products of Formula (I), wherein: there was no prior art of record that anticipated or rendered obvious the elected species and therefore the scope of the subject matter was extended or broadened in pursuant to M.P.E.P. § 803.02.
The prior art search was extended to include the full scope of elected claim 1.
IV. Rejections
35 USC § 103 - OBVIOUSNESS REJECTION
The following is a quotation of 35 U.S.C. § 103(a) that forms the basis for all
obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Graham v. John Deere Co. set forth the factual inquiries necessary to determine obviousness under 35 U.S.C. §103(a). See Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Specifically, the analysis must employ the following factual inquiries:
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 1, 9-11, 19-21, 23-25, 28-29, 32, 57, 59, 60 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu, et al. (US 20130065856 A1) or Lai, et al. (US 20180265530 A1) in view of Makadia, et al. (Polymers 2011, 3, 1377-1397), Hunt (Curr HIV/AIDS Rep (2012) 9: 139-147) and Wrench ((2017). Antiretrovirals and Steroids Chart). Applicants claim
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The Scope and Content of the Prior Art (MPEP §2141.01)
Liu, et al. teaches tenofovir alafenamide hemifumarate and its use in treating HIV infection and HBV infection (see page 3, paragraph [0040]). The prior art teaches that tenofovir alafenamide hemifumarate can be administered by any route appropriate to the condition to be treated but is generally is administered orally (see page 3, paragraph [0041]). Tenofovir alafenamide hemifumarate is preferably administered as part of a pharmaceutical composition or formulation which can comprise one or more pharmaceutically acceptable carriers/excipients and optionally other therapeutic ingredients (see paragraph [0045]). Tenofovir alafenamide hemifumarate can be formulated into a tablet, troche, pill capsule or the like and the prior art’s invention include sustained-release preparations and devices as a possible oral formulation (see paragraph [0046]). The prior art further teaches the following:
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Lai, et al. teaches various crystalline forms of salts of tenofovir alafenamide and its use in treating viral infections (see abstract). The prior art teaches the following crystalline forms: tenofovir alafenamide hemipamoate Form I, tenofovir alafenamide hemipamoate Form II, tenofovir alafenamide sabacate form I, tenofovir alafenamide napsylate Form I, tenofovir alafenamide orotate Form I, tenofovir alafenamide orotate Form II, tenofovir alafenamide orotate Form III, tenofovir alafenamide vanillate and tenofovir alafenamide bis-xinafoate (See paragraphs [0016]-[0033]). The prior art also teaches that crystalline forms of salts of tenofovir alafenamide may provide the advantage of bioavailability and stability, suitable for use as an active ingredient in a pharmaceutical composition (see paragraph [0059]).
Hunt teaches that persistent immune activation and inflammation despite sustained antiretroviral therapy (ART)-mediated viral suppression is a major challenge of the modern HIV treatment era. Inflammatory markers remain abnormally elevated in many HIV-infected individuals and can predict subsequent mortality and non-AIDS morbidities including cardiovascular disease. Soluble markers of type I interferon responses (i.e., IP-10, IFN-α levels), monocyte activation and both inflammation and coagulation also remain higher in HIV-infected individuals maintaining ART-mediated viral suppression than in HIV-uninfected individuals (See page 140). The prior art teaches that chronic inflammation has long been proposed as a common pathophysiologic process increasing the risk of earlier mortality and several chronic diseases associated with aging in HIV-uninfected individuals.
Wrench teaches a chart that shows which antiretrovirals can be safely co-administered with steroids and possible side effects that can occur, if any. The chart shows that Tenofovir can be safely co-administered with all of the listed corticosteroids including dexamethasone, methylprednisolone, etc. in all preparations
Makadia, et al. teaches the use of poly lactic-co-glycolic acid (PLGA) as a biodegradable controlled drug delivery carrier. PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. PLGA is a biocompatible and biodegradable polymer that exhibits a wide range of erosion times, has tunable mechanical properties and is FDA approved (see the abstract). PLGA has shown immense potential as a drug delivery carrier. PLGA is physically strong and is most popular among the various available biodegradable polymers because of its long clinical experience, favorable degradation characteristics and possibilities for sustained drug delivery. The prior art teaches that biodegradable polymers are natural or synthetic and are degraded in vivo, either enzymatically or non-enzymatically or both to produce biocompatible, toxicologically safe by-products which are further eliminated by the normal metabolic pathways (see page 1378). The prior art further teaches examples of PLGA (e.g. PLGA 85:15) that were tested to show the degradation time of each polymer (see page 1387). It has been shown that PLGA can easily be formulated into the drug carrying devices at all scales (i.e. nanospheres, microspheres, millimeter sized implants), can encapsulate a wide range of drugs, peptides or proteins and can be delivered over different periods of time with diverse routes of delivery (see page 1390).
The Difference Between the Prior Art and the Claims (MPEP §2141.02)
The difference between the prior art of Liu, et al. or Lai, et al. and the instant invention is that both prior art does not teach a composition comprising tenofovir alafenamide or a salt thereof, a biodegradable polymer and an anti-inflammatory agent. The above prior art references teach compositions comprising tenofovir alafenamide that could be in prepared into various types of formulations (e.g. controlled release preparations or devices).
The prior art of Wrench teaches that tenofovir can be safely co-administered with corticosteroids.
The prior art of Hunt teaches how chronic inflammation is a concern in HIV treated patients.
The prior art of Makadia teaches that biodegradable polymers are well-known and successfully used for preparing controlled release formulations.
Prima Facie Obviousness-The Rational and Motivation (MPEP §2142-2413)
In Ex parte Douros, 163 U.S.P.Q. 667 (P.T.O. Bd. App. 1968), it was well established that it is obvious to add a carrier to an obvious compound. Tenofovir alafenamide is a well-known compound that has been shown to successfully treat HIV infection. Applicants have added a biodegradable polymer (i.e., a carrier) to this compound to form a pharmaceutical composition which is well within one of ordinary skill in the art when trying to prepare a controlled release formulation. For example, the use of PLGA is common practice in the drug delivery field because of its beneficial characteristics and properties (e.g. ease of formulation, controlled release, etc. ) as shown in Makida, et al.
It was also known in the art that tenofovir can be safely co-administered with a corticosteroids (e.g. dexamethasone). One of ordinary skill in the art would want to co-administer the two agents because Hunt teaches that chronic inflammation has been a known side effect of sustained antiretroviral therapy mediated viral suppression and if untreated could result in earlier mortality and/or several chronic diseases.
For example, it is obvious to prepare a composition comprising tenofovir alafenamide and an anti-inflammatory agent (i.e., corticosteroid) with a reasonable expectation of success since the Wrench prior art reference has shown that both can be safely administered together and Hunt provides the motivation of why one of ordinary skill in the art would co-administer the two agents. As stated above, adding a known carrier to the combination of tenofovir alafenamide and a corticosteroid would be considered as obvious and well within one of ordinary skill in the art. Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to prepare pharmaceutical compositions comprising tenofovir alafenamide and an anti-inflammatory agent with a biodegradable polymer based on the teachings of the preferred embodiments in the prior art. A strong prima facie obviousness has been established.
V. Objection
Dependent Claim Objections
Dependent Claims 26, 45, 47, 49, 53 and 55 are objected to as being dependent upon a rejected based claim. To overcome this objection, Applicant should rewrite said claims in an independent form and include the limitations of the base claim and any intervening claim.
VI. Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shawquia Jackson whose telephone number is 571-272-9043. The examiner can normally be reached on 6:30 AM-3:00PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Adam Milligan can be reached on 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHAWQUIA JACKSON/Primary Examiner, Art Unit 1626
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