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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicants’ election of Group I (claims 1-2, 4-12, 14, 16 and 18-20) drawn to a thermosensitive polymer having a structure of formula (I-2), is acknowledged. Applicants’ election for the species of the structure of formula I-2 with variables E, L, A, W< B and R1 defined in the structure:
PNG
media_image1.png
152
618
media_image1.png
Greyscale
, is acknowledged. The elections were made without traverse.
As the requirement for restriction is deemed proper, it is maintained and hereby made FINAL.
Claims 13, 15, 21 and 24 are hereby withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, and non-elected species of the invention, there being no allowable generic or linking claim. The instant claims have been examined commensurate with the scope of the elected invention, and the elected species of the invention. Applicants timely responded to the restriction/election requirement in the reply filed 11/4/25.
Accordingly, claims 1-2, 4-12, 14, 16 and 18-20 are under current examination.
Status of Claims
A new claim set was filed on 11/4/25; however, there were no amendments; only status identifier changes to the newly withdrawn claims 13, 15, 21 and 24.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-2, 4-12, 14, 16 and 18-20 are rejected under 35 U.S.C. 112(b), 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “ring E is selected from a group consisting of aryl and heteroaryl”, and the claim also recites “preferably, ring E is selected from group consisting of C6-C12 aryl and 5-10 membered heteroaryl”; “more preferably, ring E is selected from the group consisting of phenyl, pyridinyl, pyrazinyl, pyrazolyl, triazolyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, imidazolyl, indazolyl and benzimidazolyl;” and “more preferably, ring E is selected from phenyl”, all of which are the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Examiner’s note: the same scenario occurs in claim 1 for the variables: m, n and a and claim 2, 5-8, 12-14 and 20, wherein “preferably”, “more preferably” and “still more preferably” are recited.
Claims 16 and 18 are unclear because they depend directly or indirectly from canceled claim 3. It is therefore, unclear what is encompassed by the composition claims 16 and 18. It is noted, that claims must be given their broadest reasonable interpretation in light of the specification (See MPEP §2111) and therefore, for purposes of compact prosecution, the abovementioned claims are being interpreted as dependent from claim 1. It is suggested to amend claims 16 and 18 to “The composition of claim 1…” in order to obviate this rejection.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefinite concerns outlined above.
Claim Rejections - 35 USC § 112(d)
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.
Claim 14 is 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. The body of claim 14 is entirely within “preferably” or “more preferably” phrases and in view of the 112b rejection above, the broadest reasonable interpretation includes wherein those limitations are required or not required by the claim. The interpretation that does not require the limitations recited after “preferably” and “more preferably” does not further limit the claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-2, 4-12, 14 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Sol–gel transition behavior of biodegradable three-arm and four-arm star-shaped PLGA–PEG block copolymer aqueous solution. J. Polym. Sci. A Polym. Chem., 44: 888-899, 2006), in view of Bozhen (CN 102477155; published: 5/30/12).
The English language machine translation of ‘155 is attached herein. The passages cited below which indicate the teachings of the ‘155 publication are based on its English translation.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Lee is directed to temperature-sensitive biodegradable 3- and 4-arm star-shaped poly(DL-lactic acid-co-glycolic acid-b-ethylene glycol) polymers (Abstract).
With regards to the elected species:
PNG
media_image2.png
104
506
media_image2.png
Greyscale
and instant claims 1-2, 4 and 6-11 (claimed variables A, W, B and R1 of the polymer), Lee teaches the synthesis of a 4-arm star shaped polymer with the following reaction scheme:
PNG
media_image3.png
776
838
media_image3.png
Greyscale
, wherein the product has a different core (claimed variables E-L-) but reads on the elected species with regards to the number of arms and the monomers within each arm (i.e., PLGA-PEG which reads on the claimed hydrophobic block A, hydrophilic block B and the bond W between A and B; and –(CH2CH2O)n-CH3) reads on the claimed –(B)n-R1 which are identical on each arm) (Scheme 1). Lee teaches that the abovementioned polymer has an average-number of monomeric units in one arm of 4-arm PLGA was varied by 9 and 11 repeat units, and in case of 4-arm PLGA9, the mole ratio of DL-lactide to glycolide ([LA]/[GA]) was varied with 50:50,75: 25, and 90:10 (p. 890).
With regards to instant claim 12, Lee teaches wherein the Mw/Mn reads on the instant range of less than 2 (e., 1.22 in the last line of Table 2).
With regards to instant claim 14, and in view of the above 112b and 112d rejections, the broadest reasonable interpretation of the claim includes wherein the limitations recited after “preferably” and “more preferably” are not required by the claim. With that interpretation, the teachings of Lee read on the claim.
With regards to instant claims 14 and 19, as the title reveals, Lee teaches wherein the abovementioned PLGA-PEG star-shaped copolymers are in aqueous solution wherein it has a sol-gel transition behavior (Title).
With regards to instant claim 20, Lee teaches that the abovementioned 4-arm polymers undergo a sol-gel transition as temperature increases and wherein the temperature is within the claimed range (see Fig. 6, 8-9 and Sol-Gel Transition Behavior section).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Lee does not teach wherein the core of the 4-arm star-shaped polymer has the claimed core of
PNG
media_image4.png
80
56
media_image4.png
Greyscale
which comes from a pyromellitic dianhydride starting material, as required by instant claims 1, 4-5, 9 and 11 (claimed variables E-L-). However, this deficiency is cured by Bozhen.
Bozhen is directed to the preparation method of multi-arm polyamide polymers (Title). Bozhen teaches that an initiator refers to a monomer or oligomer containing multiple functional groups that can react with an amino group (-NH) or a carboxyl group (-COOH); the number of functional groups carried by the initiator controls the multi-arm star polymer (p. 2). Bozhen teaches that the initiator is selected from 1,2,4-benzenetricarboxylic anhydride, pyromellitic dianhydride, diethylenetriamine, triethylenetetramine, 1,3-propanediaminetetraacetic acid or diethylenetriaminepentaacetic acid (claims and p. 2). That is, Bozhen teach forming a 4-arm star-shaped polymer with a different initiator (e.g., pyromellitic dianhydride), which upon reaction with the PLGA monomors form a
PNG
media_image4.png
80
56
media_image4.png
Greyscale
core with the monomers attached to each of the 4 arms.
Lee does not teach the specific monomer units: denoted n, x and y in the elected species (see structure above) as required by the claims. More specifically, Lee does not teach wherein n is 12, x is 4 and y is 16. Although Lee teaches a range of these variables. As indicated in MPEP §2144.05(I): “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.”
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Lee and Bozhen are both directed to 4-arm star-shaped polymers. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the invention was effectively filed, to modify the 4-arm star-shaped polymer of Lee with the core taught by Bozhen to achieve the predictable result of obtaining a composition suitable for producing a 4-armed polymer. One of ordinary skill in the art would have been motivated to do so because Bozhen teach that the simplicity, convenience and easiness in implantation and the structure and property of the core of the obtained multi-arm star polymer are controllable; the structure is flexible and adjustable (Abstract).
In addition to the teaching of overlapping ranges, the Examiner also finds the elected species monomer amounts prima facie obvious in view of the teachings of Lee. The monomer amount (n, x and y variables in the elected species) is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount in order to best achieve the desired results as such would provide advantageous micelle formation. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Lee teaches that with increasing the molecular weight and the relative hydrophobicity of hydrophobic PLGA block, critical micelle temperature (CMT) decreased (Abstract). On the other hand, at high concentration, two types of 3-arm and 4-arm PLGA–PEG showed sol–gel–sol transition behavior as the temperature was increased (Abstract). The Examiner considers it prima facie obvious to optimize the amounts of any biologically active agent to achieve their known biological effect, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amounts of each monomer would impact the ability to form a micelle and therefore be an optimizable variable.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claims 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Sol–gel transition behavior of biodegradable three-arm and four-arm star-shaped PLGA–PEG block copolymer aqueous solution. J. Polym. Sci. A Polym. Chem., 44: 888-899, 2006), in view of Bozhen (CN 102477155; published: 5/30/12) as applied to claims 1-2, 4-12, 14 and 19-20 above, and further in view of Movassaghian et al. (WIREs Nanomed Nanobiotechnol 2015, 7:691-707).
The English language machine translation of ‘155 is attached herein. The passages cited below which indicate the teachings of the ‘155 publication are based on its English translation.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Lee is directed to temperature-sensitive biodegradable 3- and 4-arm star-shaped poly(DL-lactic acid-co-glycolic acid-b-ethylene glycol) polymers (Abstract).
Lee teaches the limitations of instant claims 1-2, 4-12, 14 and 20 (see above rejection for details).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Although Lee teaches that its studies of the abovementioned polymers, which form micelles, indicate the possibility of being used as an injectable drug delivery carrier, they do not teach an embodiment that further comprises a drug or bioactive agent and as an injectable composition, as required by instant claim 16 and 18. Lee also teaches However, using polymeric micelles as drug delivery vehicles was known and routinely used in the prior art as Movassaghian.
Movassaghian is directed to applications of polymer micelles for imaging and drug delivery (Title). Movassaghian teaches that polymeric micelles, self-assembling nano-constrcuts of amphiphilic copolymers, are widely considered as convenient nano-carriers for a variety of applications, such as diagnostic imaging, and drug and gene delivery (Abstract). They show a wide variety of favorable properties including biocompatibility, longevity, high stability in vitro and in vivo, capacity to effectively solubilize a variety of poorly soluble drugs, changing the release profile of the incorporated pharmaceutical agents, and the ability to accumulate in the target zone based on the enhanced permeability and retention effect (Absract).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Lee and Movassaghian are both directed to 4-arm star-shaped polymers. Based on these teachings, It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the composition of Lee by incorporating drugs in the micelle and delivering via an injection to achieve the predictable result of obtaining enhanced drug delivery. One of ordinary skill in the art would have been motivated to do so because ??? teach that it is advantageous for the following reasons: biocompatibility, longevity, high stability in vitro and in vivo, capacity to effectively solubilize a variety of poorly soluble drugs, changing the release profile of the incorporated pharmaceutical agents, and the ability to accumulate in the target zone based on the enhanced permeability and retention effect (Absract).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached Monday-Friday 8:00-5:00.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached at 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GENEVIEVE S ALLEY/Primary Examiner, Art Unit 1617