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 .
Election/Restrictions
Applicant’s election without traverse of Trypan Blue and internal limiting membrane (ILM) in the reply filed on November 25, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Upon search and examination of the claims, the internal limiting membrane (ILM) and epiretinal membrane (ERM) were found to be obvious variants of each other.
Claim Objections
Claim 1 objected to because of the following informalities: there is no period at the end of the claim. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: a closing parenthesis is missing immediately before the period at the end of the claim. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: it appears a punctuation mark such as a comma is missing after “(ILM)” given that the ILM and the ERM are two separate structures. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 – 4 and 9 – 11 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 appears to end with the clause “where the diglycerol or triglycerol increases the staining contrast of the dye” but the basis for the comparison of the required alteration staining contrast is not set forth. Given the lack of period at the end of the claim, that text could be missing from the claim but as currently set forth, with setting forth the basis of the comparison in staining contrast, the metes and bounds of the claims cannot be determined. The dependent claims fall therewith. Please clarify.
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 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.
Claim(s) 1 – 4 and 9 – 11 are rejected under 35 U.S.C. 103 as being unpatentable over Melles et al. (US 2013/0045167) in view of Li et al. (Br J Ophthal, 2003), Fox (WO 2014/123844), Vowles (US 2013/0312897) and Coroneo (US 6,372,449).
Melles et al. discloses staining compositions comprising a vital dye and a density increasing compound selected from the group consisting of water-soluble polymers and small inert molecules (whole document, e.g., abstract). Increasing the density of the staining composition was found to decrease the time it took for staining of the ocular structures to occur (¶ [0018]) while also not showing an effect or at least not a significant detrimental extent on the stability of the vital dye (¶ [0020]). Additionally, a composition having a sufficiently high viscosity may show a low mixing rate with rinsing liquids used during the procedures to allow for a high and narrowly localized concentration of the dye, allowing for a decrease in the time required for the dye to penetrate the ocular tissues and/or reduce the risk of undesired staining of surrounding tissues (¶ [0048]). Exemplary viscosity values are also given in ¶ [0048]. Preferably, the density increasing compound does not affect, or at least not significantly affects, the staining properties of the dye used (¶ [0029]) and is also preferably nonionic due to the difficulties in controlling the osmolarity of the staining composition (¶ [0030]). In case the density increasing compound is a water soluble polymer, in particular PEG, the concentration is preferably at least 1 wt% and more preferably 2 – 10 wt%, more preferable 3 – 6 wt% based on the total weight of the staining composition (¶ [0047]). The presence of polyethylene glycol (PEG) was found to have a beneficial effect on vital dye stability, with this beneficial effect being observed in particular for trypan blue and PEG staining compositions (¶ [0020]). The concentration of dye in the composition is preferably 0.001-2 wt% and a number of narrower ranges are also disclosed, with 0.1 – 0.5% being the most preferable (¶ [0052]). For Trypan Blue (TB) specifically, a range of 0.05 – 0.5 wt% is disclosed (¶ [0053]).
The administration of the stain to an eye to stain a structure such as the internal limiting membrane (ILM) is not disclosed.
Li et al. discloses that TB (Trypan blue) has been used to stain the anterior lens capsule during cataract surgery at a relatively low concentration and proved to be effective and safe (p 216, col 1, ¶ 3). The use of TB for intraoperative staining of the ILM and macular pucker membrane was evaluated (p 216, col 1, ¶ 3). TB has already been tested for biocompatibility and CE approval for intraocular use and a commercially available 0.06% TB solution in phosphate buffered sodium chloride was used (p 216, col 2, ¶ 5). The solution was injected into the air filled vitreous and removed after 2 minutes and resulted in the ILM and ERM being stained a faint blue color (p 217, col 1, ¶ 2). In all 14 eyes studied, the ILM or ERM was adequately stained and visualized (p 217, col 2, ¶ 3) with a distinct contrast between the stained ILM/ERM and unstained retina and allowed the removal of the stained tissues (p 218, col 1, ¶ 1).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate use a TB containing solution as in Melles et al. during ocular surgery to stain the ILM and/or ERM of a subject as taught by Li et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the use of a 0.06% concentration of TB solution was sufficient to stain and visualize these tissues without the staining the retina to identify the ILM and/or ERM with a blue color to aid in removal of these tissues but not the unstained retina. Melles et al. discloses the increased staining contrast for the compositions comprising a density increasing compound and the formulation of Li et al. that does not contain such ingredients and was already able to stain such structures. The person of ordinary skill in the art would reasonably expect increased staining contrast compared to that solution upon addition of a density increasing compound given the disclosure of Melles et al.
The presence of diglycerol or triglycerol in the dye composition used to stain the ILM and/or ERM is not disclosed.
Fox discloses a composition for staining cytological material comprising a cationic dye component, a hygroscopic polyol and optional a water-water soluble solvent, water or water miscible solvent (whole document, e.g., abstract). While cationic dyes such as those shown on p 8 are preferred (p 9, ln 9), anionic dyes such as those shown on p 10 can also be used in the cytological staining compositions (p 9, ln 25 – 26). Useful hygroscopic polyols include glycerol, diethylene glycol, triethylene glycol and polyethylene glycol (p 11, ln 21 – 22) with useful amounts of the hygroscopic polyol being less than about 10% w/w of the total composition (p 12, ln 4 – 8).
Vowles discloses prosthetic menisci of the correct shape that are implanted into the knee in a collapsed and compact form whose interior is then injected with a liquid of high viscosity or polymer material setting to a gel or solid consistency to inflate the menisci structure to conform precisely to the external shape of the tibial plateau and femoral condyle (¶ [0027]). A wide range of biocompatible, viscous liquids or liquids settable to a gel or rubbery solid are well known in the art with given examples of biocompatible viscous liquids being diglycerols, polyglycerols or silicones (¶ [0073]).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use a polyol such as diglycerol as the density and/or viscosity increasing agent in the vital dye compositions of Melles et al. that are administered during surgery to stain the ILM and/or ERM. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Vowles discloses that diglycerol is a biocompatible, viscous liquid that is suitable for injection into subjects. Fox discloses that both diglycerol and triglycerol are suitable for use in compositions for cytological staining and one of ordinary skill in the art would reasonably expect that such compounds would also increase the density of the composition (see accompanying products sheets for diglycerol and triglycerol from biosynth.com, accessed January 13, 2025 indicating that the density of each of these materials is greater than 1.0 g/cm3). Melles et al. discloses that dye compositions of increased density and viscosity provide for benefits when used to stain ocular tissue during various procedures and the identify the compound used to increase the density can have an impact on the stability of the dye composition. Diglycerols are non-ionic and therefore can be used to increase the density without affecting the osmolarity of the final composition. One of ordinary skill in the art would routinely optimize the amount of the density increasing compound to provide a final solution with an optimal viscosity. As such, the amount of a specific ingredient in a composition 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 reasonably would expect success and there is no evidence of record as to the criticality of the claimed amounts. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors such as the particular dye and intended use of the dye solution (e.g., in vitro or in vivo tissue staining or the particular tissue being stained). As the materials of Melles et al., Vowles and Fox are injected into and/or brought into contact with the tissue of a subject and to minimize the risk of infection, the person of ordinary skill in the art would provide the compositions in sterile form.
There is no explicit disclosure that sterilized materials were used during the surgical procedure.
Coroneo discloses identification of intraocular membranes and structures within the eye using a trypan blue solution (whole document, e.g., abstract). Generally, such trypan blue solutions comprise 0.05% to 3 % w/w trypan blue although 0.1 – 0.3% w/w is the narrowest more preferable range disclosed (col 2, ln 26 – 29). The compositions are generally isotonic and for introduction into the eye are sterile, buffered and free of particulate material (col 2, ln 32 – 35).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use sterilized compositions such as that comprising Trypan Blue and a density increasing compound such as di- or tri-glycerol during the surgical procedure. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because sterile compositions are generally used for introduction into the eye to stain the tissues of the eye to minimize the risk of infection from the dye containing composition. This would be known to one of ordinary skill in the art and Coroneo explicit discloses that Trypan blue containing compositions introduced into the eye are generally sterile.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618