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 .
Claim Objections
Claim 35 is objected to because of the following informalities: on line 2, applicant need to change “and” to --- or ---. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 31 is 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 31 recites the limitation "the biodegradable and biocompatible polymer" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim because claim 30 (from which claim 31 depends) recites that the thermosensitive hydrogel comprises at least one biodegradable and biocompatible polymer. It is unclear if “the biodegradable and biocompatible polymer” in claim 31 refers to the one biodegradable and biocompatible polymer or the more than one biodegradable and biocompatible polymer required by claim 30, or if “the biodegradable and biocompatible polymer” refers back to all the biodegradable and biocompatible polymers that can be part of the composition in claim 30 or not.
Instant rejection can be overcome by changing "the biodegradable and biocompatible polymer" in claim 31 to --- the at least one biodegradable and biocompatible polymer ---.
Claim Rejections - 35 USC § 103
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.
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 29-36 and 38-48 are rejected under 35 U.S.C. 103 as being unpatentable over Ye et al (US 2012/0277199 A1) in view of Al-Jilaihawi (US 2016/0310699 A1), Curley et al (US 2014/0275977 A1), Kim et al (US 2013/0164224 A1), Lorenzini et al (US 2001/0056206 A1) and Schwarz et al (US 2011/0076231 A1) (with Wikipedia webpage https://en.wikipedia.org/wiki/Otitis_media, which is being cited here merely to support the Examiner’s assertion that acute otitis media has as its primary symptoms, ear pain, fever and reduced hearing and that either viruses or bacteria may be involved).
Ye teaches ([0004], [0186] and claim 1) a syringeable (injectable) pharmaceutical formulations comprising an effective amount of active agent and a thermosensitive polymer comprising polyoxyethylene and polyoxypropylene copolymers. Ye teaches ([0025] and [0026]) that the active agent can be an antibiotic, which examples include ciprofloxacin, vancomycin and linezolid.
Specifically, Ye teaches ([0401]) the following formulation:
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Ye’s Formulation C shown above contains 15 mg of Ciprofloxacin, and Ciprofloxacin is one of the examples given by applicant for an antibiotic that can be used in their invention (see [0043] of present specification). Thus, Ye’s 15 mg of Ciprofloxacin teaches instant component (a) an effective amount of an antibiotic.
With respect to instant (b) a thermosensitive hydrogel, Ye teaches ([0012] and [0335]) that its formulation comprises about 14.5-25 wt.% of the thermosensitive polymers, which examples include Poloxamer 407. It would have been obvious to use 14.5-25 wt.% of Poloxamer 407 (instant biodegradable and biocompatible polymer of claims 30-31) in its Formulation C with a reasonable expectation of success. Thus, Ye teaches instant component (b) a thermosensitive hydrogel. Furthermore, the range 14.5-25 wt.% for the amount of the thermosensitive polymer (such as Poloxamer 407) overlaps with instant range 2-20 wt.% for the amount of poloxamer 407 (as claimed in instant claim 31), thus rendering instant range prima facie obvious. In the case “where the [claimed] ranges overlap or lie inside ranges disclosed by the prior art,” a prima facie case of obviousness would exist which may be overcome by a showing of unexpected results, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
With respect to instant (d) optionally, at least one pharmaceutically acceptable excipient, Carboxymethylcellulose contained in Ye’s Formulation C teaches instant pharmaceutically acceptable excipient (see [0073], [0076] and [0078] of present specification). Thus, Ye teaches instant component (d).
With respect to instant (c) a radio-contrast agent, Ye teaches ([0271) that any of its formulations (such as Formulation C above) is used in combination with an imaging device to monitor or survey the condition being treated and that its formulation comprises Gadolinium-based dyes, iodine-based dyes, barium-based dyes or the like for visualization of disease progression and/or formulation penetration. Although Ye does not explicitly teach specific materials that can be used as its dyes, Iohexol is a well-known iodine-based dye used in imaging, as evidenced by Al-Jilaihawi ([0062]). Furthermore, as evidenced by Curley et al ([0059]), iohexol is a non-ionic dye used as a contrast agent that is known for its stability at elevated temperatures. Kim et al also teaches ([0019]) iohexol as a contrast agent that is known for having generally lower chemical toxicity and neurotoxicity than other contrast agents and known to have a very wide adaptive domain. Kim teaches that for such reason, iohexol is the best-selling contrast agent in the world. Lorenzini et al ([0002]) teaches that non-ionic contrast agents, such as iohexol, are useful as contrast enhancing agent for X-ray, MRI and angiography and that such compounds have a lower frequency of adverse reactions in patients during intravenous injection than many ionic contrast agents. Besides, it is already known in the art to use Poloxamer 407 (used in Ye’s Formulation C shown above) and Iohexol together (see Schwarz et al, [0160], where it is shown that poloxamer 407 is used together with Omnipague 300 (tradename for Iohexol)). Based on the teachings of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz, it would have been obvious to one skilled in the art to use Iohexol (instant radio contrast agent of claim 43) in Ye’s Formulation C (as its iodine-based dye) with a reasonable expectation of achieving visualization of disease progression and/or formulation penetration while achieving all those advantages of using iohexol as taught by the references cited above. Therefore, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz teaches or renders obvious instant component (c).
Thus, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 29-31 and 43.
With respect to instant claims 32 and 33, Ye teaches (claim 1) that its formulation has a gelation temperature between about 14-42oC, which overlaps with instant range 32-38oC, thus rendering instant range prima facie obvious. In re Wertheim, supra. Also, when the gelation temperature is about 14-42oC, this means that Ye’s formulation is an aqueous solution below the range of 14-42oC, which also overlaps with instant range (4-25oC), thus rendering instant range prima facie obvious (furthermore, Ye’s Table 7 shows that the gelation temperature can be 37oC, 35.4oC, 33.5oC, 31.2oC, 28.9oC or 27.6oC, depending on the ratio of Poloxamer 407 to Poloxamer 188). Thus, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 32 and 33.
With respect to instant claim 34, since Ye in view of the other prior arts cited above teaches instant composition of claim 29, Ye’s Formulation C modified according to the teachings of the other cited prior arts would naturally remain liquid for at least 3 hours at room temperature as recited in claim 34. Thus, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 34.
With respect to instant claims 35, 36, 38, 40 and 41, although Ye uses ciprofloxacin as its antibiotic in its Formulation C, as discussed above at the beginning, Ye teaches ([0025]-[0026] and claim 28) the equivalence or interchangeability of ciprofloxacin, vancomycin and linezolid as its active agent. Ye also teaches ([0027]) that its antibiotic used in its Formulation C (i.e., ciprofloxacin) can be used in the amount of 0.1-20 wt.%. Therefore, it would have been obvious to one skilled in the art to use Vancomycin or Linezolid in Ye’s Formulation C in the amount of 0.1-20 wt.% (which overlaps with instant ranges of claims 38 and 41), with a reasonable expectation of success. Thus, Ye’s teaching in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 35, 36, 38, 40 and 41. Furthermore, with respect to instant claims 39 and 42, it is the Examiner’s position that about 0.1-20 wt.% of Linezolid or Vancomycin would correspond to (or at least overlap with) the ranges for the total dose of Linezolid and Vancomycin specified in instant claims 39 and 42. Alternatively, since Ye uses 15 mg of Ciprofloxacin (its antibiotic) in its Formulation C, it would have been obvious to one skilled in the art to use 15 mg of Linezolid or Vancomycin (instead of 15 mg of Ciprofloxacin) in Ye’s Formulation C with a reasonable expectation of success. Thus, Ye’s teaching in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 39 and 42.
With respect to instant claims 44 and 45, since Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz teaches instant injectable pharmaceutical composition of claim 29, Ye’s Formulation C modified according to the teachings of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz would naturally be capable of being formulated for administering to a bone, joint, ligament or tendon associated with the spine, wherein the bone, joint, ligament, or tendon associated with the spine is further associated with a cervical, thoracic, lumbar or sacral vertebra, as recited in claims 44 and 45. Thus, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 44 and 45.
With respect to instant claims 46 and 47, Ye teaches ([0157] and [0159]) that its inventive formulation (such as Formulation C) can be used for the treatment of otic disorders such as otitis media (middle ear infection) and can be administered via intratympanic injection. As evidenced by the Wikipedia webpage https://en.wikipedia.org/wiki/Otitis_media, (see the first two paragraphs) acute otitis media has as its primary symptoms, ear pain, fever and reduced hearing and that either viruses or bacteria may be involved. Thus, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claims 46 and 47.
With respect instant claim 48, Ye teaches (see the paragraph [0380] under “Kits/Articles of Manufacture”) that its formulations are either manufactured as ready to use single component solutions or as multi-component kits that are administered to an individual in need thereof. Thus, Ye in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz renders obvious instant claim 48.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Ye et al (US 2012/0277199 A1) in view of Al-Jilaihawi (US 2016/0310699 A1), Curley et al (US 2014/0275977 A1), Kim et al (US 2013/0164224 A1), Lorenzini et al (US 2001/0056206 A1) and Schwarz et al (US 2011/0076231 A1), as applied to claim 36 above, and further in view of Lichter et al (US 2010/0036000 A1).
Ye does not teach instant cyclodextrin of claim 37. However, as evidenced by Lichter ([0476]-[0479]), it is known in the art that cyclodextrin can be used as a solubilizer for antimicrobial agents to assist or increase the solubility and that the concentration or the amount of cyclodextrin used will vary depending on the need. It would have been obvious to one skilled in the art to add cyclodextrin to Ye’s formulation in order to assist or increase the solubility of its antibiotic in the amount necessary to solubilize the antibiotic. Determining the optimum amount of cyclodextrin necessary to solubilize the antibiotic (such as linezolid, vancomycin or ciprofloxacin) would be within a realm of one of ordinary skill in the art, and such determined amount for the cyclodextrin necessary to solubilize the antibiotic (such as linezolid, vancomycin or ciprofloxacin, which are instant antibiotics) would correspond to or at least overlap with instant range of 15-35 wt.% (thus rendering instant range prima facie obvious. In re Wertheim, Supra). Thus, Ye’s teaching in view of Al-Jilaihawi, Curley, Kim, Lorenzini and Schwarz, and further in view of Lichter renders obvious instant claim 37.
Double Patenting
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.
Claims 29-36, 38, 39, 43-45 and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 7-9 and 13 of U.S. Patent No. 11,517,574 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 1 of Pat.’ 574 teach the followings:
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Poloxamer 407 of claim 1 shown above teaches instant biodegradable and biocompatible polymer, and iohexol of claim 1 shown above teaches instant radio-contrast agent. Thus, claims 1, 2, 5, 7-9 and 13 of Pat.’574 render obvious instant claims 29-36, 38, 39, 43-45 and 48.
Claim 37 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 7-9 and 13 of U.S. Patent No. 11,517,574 B2 in view of Lichter et al (US 2010/0036000 A1).
Claims of Pat.’574 do not teach instant cyclodextrin of claim 37. However, as evidenced by Lichter ([0476]-[0479]), it is known in the art that cyclodextrin can be used as a solubilizer for antimicrobial agents to assist or increase the solubility and that the concentration or the amount of cyclodextrin used will vary depending on the need. It would have been obvious to one skilled in the art to add cyclodextrin to the formulation of claim 1 of Pat.’574 which contains linezolid (an antibiotic) in order to assist or increase the solubility of linezolid in the amount necessary to solubilize linezolid. Determining the optimum amount of cyclodextrin necessary to solubilize linezolid would be within a realm of one of ordinary skill in the art, and such determined amount for the cyclodextrin necessary to solubilize linezolid would correspond to or at least overlap with instant range of 15-35 wt.% (thus rendering instant range prima facie obvious. In re Wertheim, Supra). Thus, claims of Pat.’574 in view of Lichter render obvious instant claim 37.
Claims 29-36, 38, 39 and 43-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 12 and 17 of copending Application No. 18/700,578 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reason:
Claims 1-3 of App.’578 teaches a method for treating low back pain comprising administering a therapeutically effective amount of antibiotic, which is linezolid, to one or more targeted sites in the spine of a patient, wherein the linezolid is formulated in a thermosensitive hydrogel delivery carrier composed of poloxamer 407 and iohexol (instant radio-contrast agent) and wherein the thermosensitive hydrogel delivery carrier is pre-prepared as a sterilized solution. Claim 5 of App.’578 teaches that the linezolid composition is administered to tendon associated with the spine. Claim 8 of App.’578 teaches that the linezolid composition is delivered to the one or more intervertebral discs using an introducer needle and an administration needle. Claims 12 and 17 of App.’578 teaches that the patient receives a single dose of the linezolid composition in each of the one or more targeted sites in the spine and teaches that the dose of the linezolid composition contains about 150 mg linezolid (thus teaching instant claim 39). Thus, claims 1-3, 5, 8, 12 and 17 of App.’578 render obvious instant claims 29-36, 39 and 43-47 (since claims of App’578 teach instant injectable pharmaceutical composition, it is the Examiner’s position that such composition would inherently satisfy instant limitations of claims 32-24).
With respect to instant claim 38, claim 4 of App.’578 teaches that linezolid is pre-prepared (as a sterilized solution) in a dose unit of about 250 mg and loaded to about 5 ml of the thermosensitive hydrogel delivery carrier prior to the administration. Assuming that 5 ml of the thermosensitive hydrogel delivery carrier is approximately equal to 5 g, this gives the concentration of linezolid to be approximately 4.76% by weight (i.e., 0.250 g / (5 + 0.250 g) x 100% = 4.76%) of the sterilized solution containing linezolid and the thermosensitive hydrogel delivery carrier. Thus, claim 4 of App.’578 renders obvious instant claim 38. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-36, 38 and 43-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29, 39-41, 43, 46 and 47 of copending Application No. 19/025,236 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reason:
Claim 29 of App.’236 teaches the following:
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The concentration range (9.5-17%) for poloxamer 407 falls within instant range of claim 31 (about 2-20 wt.%) for poloxamer 407 concentration, thus teaches instant range. Claims 39-41 of App.’236 teach that the suspension of claim 29 gels at a temperature of about 26-38oC, or about 32-36oC or about 26-32oC. Claim 43 of App.’236 teaches instant kit of claim 48. Claims 46 and 47 of App.’236 teach instant methods of claims 46 and 47. Thus, claims 29, 39-41, 43, 46 and 47 of App.’236 render obvious instant claims 29-36, 38, 43-48. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SIN J. LEE whose telephone number is (571)272-1333. The examiner can normally be reached on M-F 9 am-5:30pm.
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/SIN J LEE/Primary Examiner, Art Unit 1613 July 11, 2026
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