DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
The amendment of 12/15/2025 has been entered. Claims 29, 32-34, 49, 51-52, 56, 60-62, and 65-67 are currently pending in this US patent application and were examined on their merits.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which 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 section 102, 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 negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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, 32-34, 49, 51-52, 56, 60-62, and 64-67 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US patent application publication 2008/0227143 filed by Kosmeder et al., published 0/18/2008.
Kosmeder teaches a dye formulation that is stabilized against degradation over time and the use of the formulation to stain biological samples (see entire document, including page 1, paragraph 0002). The dye compound includes a dye stabilized by one or both of a host compound and an antioxidant (page 3, paragraph 0027). The antioxidant may be a reducible sugar like sorbitol and mannitol (page 3, paragraph 0030; cf. claims 29, 52, and 66-67 [“…one or more hygroscopic polyols”]). The antioxidant may be present at a concentration from 1 mM-1 M (page 2, paragraph 0016; cf. claims 29 and 66-67 [“…less than about 1% v/v of the total composition”]). The solvent comprises water and a polyol, which can be glycerol, in a concentration of 5-45% (v/v) (pages 3-4, paragraph 0031; cf. claims 29, 52, 56, and 66-67). The dye compound may be azure C (page 5, paragraph 0039; cf. claims 29, 49, and 64-67). The biological samples that can be stained with the dye formation can include blood and biopsy samples from tumors and can be mounted on microscope slides for treatment and/or examination (page 2, paragraph 0018; cf. claims 29, 32-34, 60-62, and 66-67; the Examiner notes that a microscope slide is a “substrate”, that Kosmeder makes no disclosure of a requirement to associate a solid cover slide with the sample, and that any blood sample would be “susceptible to” containing abnormal blood cancer cells as recited in instant claims 60-62). The process can be applied to any histological staining process (page 5, paragraph 0040; cf. claims 29 and 66-67; the Examiner notes that Kosmeder’s disclosure does not require the addition of any other staining composition to the biological sample, including anionic dyes).
However, Kosmeder does not explicitly teach staining a biological sample on a microscope slide with a composition consisting of azure C, sorbitol or mannitol, water, and glycerol in the amounts recited in instant claims 29, 51, and 63-67.
While Kosmeder does not explicitly teach staining a biological sample on a microscope slide with a composition consisting of azure C, sorbitol or mannitol, water, and glycerol, it would have been obvious to one of ordinary skill in the art to do so because Kosmeder suggests all of these elements for the staining method. One of ordinary skill in the art would have a reasonable expectation that combining azure C, sorbitol or mannitol, water, and glycerol as suggested by Kosmeder and using the composition to stain biological samples on microscope slides would successfully result in the stabilization of the dye composition and the staining of the biological samples.
Kosmeder does not explicitly teach all of the concentrations recited in instant claims 29, 51, and 63-67. However, the instantly recited concentrations would be within the realm of routine experimentation. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 part II A. It would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal concentrations of any dye compounds, antioxidants, and solvents in a staining composition for cell staining because the concentrations of all of these ingredients are art-recognized, result-effective variables known to affect the cost of the stain and its ability to effectively stain cells, which would have been optimized in the art to provide the desired staining ability and cost.
Therefore, claims 29, 32-34, 49, 51-53, 56, and 59-67 are rendered obvious by Kosmeder and are rejected under 35 U.S.C. 103(a).
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
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 was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant has traversed the above rejection of the claims under 35 U.S.C. 103(a) as being unpatentable over Kosmeder. Applicant states that Kosmeder does not teach that a simple substitution of Kosmeder’s hematoxylin in the teaching with azure C without any modification or optimization of other components can still effectively stain a biological sample (remarks, pages 6-7). This argument has been fully considered but has not been found persuasive.
The Examiner notes that Applicant has provided no evidence or argument as to why substituting azure C, as suggested by Kosmeder, into Kosmeder’s composition for staining biological samples would not be able to stain biological samples. As such, the Examiner maintains that one of ordinary skill in the art would have a reasonable expectation based on Kosmeder that using any dyes suggested by Kosmeder, such as azure C, in Kosmeder’s compositions and methods that Kosmeder teaches are for use in staining biological samples (see page 1, paragraph 0002) would be able to successfully perform the purpose that Kosmeder teaches.
Applicant states that Kosmeder uses higher concentrations of polyols than recited in the instant claims because hematoxylin is poorly soluble in water and requires the higher polyol concentration for solubility purposes. Applicant states that, therefore, lowering the concentration of polyols from the concentration range taught in Kosmeder to the instantly recited concentration range would render Kosmeder’s invention unsatisfactory for its purpose of improving the stability of dyes (remarks, page 7). This argument has been fully considered but has not been found persuasive.
The Examiner notes that Kosmeder suggests the use of azure C in the invention. Lowering the polyol concentration taught in Kosmeder would have not affected the solubility of azure C in the dye composition, and one of skill in the art would have understood this, as asserted by Applicant in the following paragraph on page 7 of the remarks of 12/15/2025. The Examiner notes that Kosmeder’s purpose is not in stabilizing hematoxylin but, rather, in providing a dye formulation that is stabilized against degradation over time and the use of the formulation to stain biological samples, as stated by Kosmeder. As such, optimization of the concentrations in Kosmeder that would not negatively affect the solubility of dyes specifically recited by Kosmeder, such as azure C, cannot be viewed as rendering Kosmeder unsatisfactory for its intended purpose.
Applicant states that the claimed method has benefits regarding the prevention of cell compression/collapse and non-flammability that are not disclosed in Kosmeder (remarks, pages 7-8). This argument has been fully considered but has not been found persuasive.
In response to applicant's argument that the recited method has particular benefits not taught by Kosmeder, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Therefore, the Examiner has maintained the rejections presented above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 03/31/2026