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 .
Claims 1,3,6,8,10,13,17-18,22,28, and 48 are under examination.
Response to Applicants Instant Set of Claims
The examiner has carefully reviewed the amendments and applicants arguments. The former rejections are withdrawn and new rejections are put forward because the recent amendments have changed the scope of the invention.
The claims now recite a liquid in which the specific gravity of the liquid can be adjusted by supplementation with a specific gravity modifying means. A specific gravity value is now listed in the claims (about 1.05 g/mL + 0.03 g/ml). It is unclear if the specific gravity value recited in the claims is referring to the specific gravity of just the liquid or the specific gravity of the liquid with the specific gravity-modifying means.
Applicants specification does teach a specific gravity for the liquid. However, the embodiments in the specification that teach that specific gravity value recited in the instant claims only refer to it encompassing the liquid, and these embodiments are silent regarding the specific gravity-modifying means. Furthermore, the specification in Figures 6a-6b and Example 5 do mention a few specific gravity values of liquid with specific gravity modifying means, (also known as density adjusted medium in the specification). However, the embodiments in the specification that list the range of the specific gravity of the liquid just refer to the liquid as a liquid and not as a density adjusted liquid or density adjusted medium as mentioned in Example 5 and Figures 6A-6B. The specification provides support for the specific gravity value recited in the claims for the liquid alone and not the liquid and the specific gravity modifying means.
The instant claims are indefinite because the claims do not clearly recite whether the specific gravity is referring to just the liquid or the liquid with specific gravity modifying means. There is written description support in applicants’ specification for the specific gravity value recited in the instant set of claims for the liquid but not a combination of the liquid and specific gravity modifying means.
Because of the recent amendments, the former 112(b) rejections have been withdrawn. However, new 112(b) and written description rejections have been added that address the recent claim amendments dated March 19, 2026.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1,3,6,8,10,13,17-18,22,28, and 48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
The claim recite that the specific gravity of the liquid is about 1.05 g/ml + 0.03 g/ml. The specification states that the specific gravity of the liquid is between about 1.0 g/ml and 1.5g/ml (Paragraphs 23 and 33 of applicants’ published specification US 2024/0002782). Paragraph 19 of the published application states, “an average density of the particles of the population, or the one or more subpopulations thereof, is the same as or within about +/- 3% of the specific gravity (e.g. density of the liquid), and the population of particles, or the one or more subpopulations thereof, are neutrally buoyant within the volume/column of liquid.” These paragraphs do not state or imply that the specific gravity amount includes the specific gravity modifying means. If it is applicants’ intent for the specific gravity value referenced in the claims to refer to the combination of the liquid and the specific gravity modifying means, then there is a written description issue because the specification does not provide support for a specific gravity amount that includes both the liquid and the specific gravity modifying means. The indefiniteness of the claims are also discussed in the 112(b) rejection below.
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 1,3,6,8,10,13,17-18,22,28, and 48 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 1ci states, “applying an energy input to the liquid to distribute the population or subpopulation of particles throughout the volume of the liquid, wherein the specific gravity of the liquid is about 1.05 g/mL + g/mL” The claim does not clearly specify if the specific gravity is the specific gravity of the liquid or the specific gravity of both the liquid and the specific gravity modifying means (adjusted specific gravity). The embodiment paragraphs that mention specific gravity ranges do not state that the specific gravity values are for the combination of the liquid and the specific gravity-modifying means (Paragraphs 19,23-24 of applicants published specification 2024/0002782). Furthermore, there are other separate sections in the specification where the specification clearly refers to density adjusted medium (liquid plus the specific gravity adjusting means) (Example 5 of the specification). Paragraphs 19,23-24 do not specifically refer to a density adjusted medium/liquid or the density adjusted medium when disclosing the specific gravity of the liquid.
Claim 1 further recites, “biasing the population or subpopulation(s) of particles upward from a lower portion of the volume of the liquid, wherein the specific gravity of the liquid is greater than unity by about 10%, 15%, 20%, 25%, 30%, 35%,40% or more, ….” This clause is also indefinite because it is unclear if the specific gravity value encompasses just the liquid or the liquid with the modifying means. The dependent claims fail to clarify whether the specific gravity refers to the specific gravity of just a liquid or the specific gravity of both the liquid and modifying means.
The dependent claims fail to clarify these issues. For example claim 10 recites “wherein an average density of the particles of the population, or the one or more subpopulations thereof, is the same as or within about +/- 3% of the specific gravity of the liquid, and the population or subpopulation(s) is neutrally buoyant within the volume of the liquid.” Claim 10 is indefinite because it is unclear if the average density of the particles is being compared with the specific gravity of the liquid or the specific gravity of the combination of the liquid and the specific gravity modifying means.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1,3,6,13,17,22, and 48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang (US 20150238974)
Wang discloses a manipulating the localization of particles, or one or more subpopulations, within a volume of a liquid (Abstract; Paragraphs 8-10), comprising: a. contacting the population of particles, or the one or more subpopulations thereof (population of seed particles), with the liquid, the liquid supplemented with a specific gravity-modifying means and having a specific gravity that is not equal to unity, wherein the liquid is homogenous, and wherein is a viscosity of the liquid is within 10% water, b. influencing buoyancy of the population of particles, or the one or more subpopulations thereof, within the volume of the liquid; and c. i. applying an energy input to the liquid to distribute the population or subpopulations of particles throughout the volume of the liquid, wherein the specific gravity of the liquid is about 1.05 g/ml + 0.03 g/ml, or ii. biasing the population of subpopulation(s) of particles upward from a lower portion of the volume of the liquid, wherein the specific gravity of the liquid is greater than unity by about 10% or more, and wherein an average density of the particles of the population, or the one or more subpopulations thereof, is lower than the specific gravity of the liquid, and the population or subpopulation(s) is biased upward toward or to a gas-liquid interface of the volume of the liquid, wherein the specific gravity of the liquid is adjusted either before or after contacting the population of particles, or the one or more subpopulations thereof, with the liquid, by varying a concentration of the specific gravity-modifying means in the liquid (Abstract, Paragraphs 17-21, 34, Figure 1) as in instant Claim 1. Wang discloses wherein the energy input is a turbulent mixing force (Paragraph 19) as in instant Claim 3. Wang discloses deactivating the energy input, wherein distribution of the population or subpopulations(s) of particles is maintained throughout the volume of the liquid after deactivating the energy input (Paragraph 27) as in instant Claim 6. Wang discloses wherein the population or subpopulation of particles is sedimented prior to contacting the population or subpopulations of particles within the liquid, and is biased upward within the volume of the liquid after coming into contact with the liquid (Figure 1, Paragraphs 17-21) as in instant Claim 13. Wang discloses potassium nitrate which is a specific gravity modifying soluble solid (Paragraph 34) as in instant Claim 17. Wang discloses wherein the population or subpopulation(s) are aggregate cells (seeds are composed of aggregate cells) (Paragraphs 17-21) as in instant Claim 22. Wang discloses wherein an increased specific gravity of the liquid corresponds to a decreased energy input to distribute the population or subpopulation(s) of particles within the volume of the liquid (Pages 2-3 of Wang) as in instant Claim 48.
The reference anticipates the claim limitations.
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.
Claims 1,3,6,8,13,17,22, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US 20150238974)
Wang applies as above to teach claims 1,3,6,13,17,22, and 48. Wang does not teach the exact cell concentration of each aliquot that is removed or how many aliquots are required to remove cells. MPEP § 2144.05 (II) states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the claimed cell concentration of each aliquot or the number of aliquots required to remove cells are critical. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Wang to try a finite number of possible concentrations of cells in each aliquot to predictably arrive at the claimed concentration through routine optimization. An artisan would have been expected to have optimized the number of aliquots needed to fully remove the segregated cells. An artisan would have a reasonable expectation of success in optimizing the cell concentrations/number of aliquots needed for cell removal because determining cell removal methods were long established in the art as determined by Wang (Paragraphs 27-29). Thus, Wang renders claim 8 obvious.
Claims 1,3,6,10,13,17-18,22,28, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US 20150238974) in view of Woodside (CA 2405881). Woodside is already of reference.
Wang applies as above to teach claims 1,3,6,13,17,22, and 48. Wang discloses that other chemicals such as potassium nitrate or sugar can be added to a liquid in order to modify the specific gravity of a liquid. Wang does not teach adding iodixanol. However, Woodside teaches that iodixanol can be added to a liquid to modify the specific gravity of a liquid (Abstract and Page 9, line 18). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have added Woodside’s liquid solution containing iodixanol to the water of Wang’s process. An artisan would have been motivated to have added iodixanol because like the potassium nitrate and sugar taught by Wang, iodixanol is able to modify the specific gravity of a liquid (Page 9, line 18 of Woodside) so that populations of cells can be separated on basis of their densities (Pages 5-9 of Woodside). There would have been a high expectation for success using the iodixanol and water components taught by Woodside in a density separation process because Woodside teaches that these components can be incorporated into a liquid used to successfully separate out cell populations with different densities (Page 9 Of Woodside) as in instant Claims 1,17-18.
Dependent Claims taught by Woodside
Woodside teaches wherein an average density of the particles of the population, or the one or more subpopulations thereof, is within about +/- 3% of the specific gravity of the liquid, and the population of subpopulation(s) is neutrally buoyant within the volume of the liquid (Page 5, lines 22-32; Page 7; Page 9, lines 20-27 of Woodside) as in instant Claim 10. The medium taught by Woodside has components that support cell growth/culture. For example, the medium has a carbon source (Page 9 of Woodside) as in instant Clam 28.
Wang can successfully separate out distinct populations of particles based on different densities by using a liquid where the specific gravity of the liquid can be adjusted by a specific gravity modifying means (potassium nitrate or sugar). Wang does not use iodixanol in its separation liquid. However, an artisan would have been motivated to have used Woodside’s separation liquid containing hetastarch, iodixanol, and water (Page 9 of Woodside) because the solution is able to successfully separate out particles based on their different densities (Pages 5-9 of Woodside). Given the teachings of the cited references and the level of skill of an artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the ordinarily skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. V. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in particle separation and cell culture.
Conclusion
All claims stand rejected.
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 LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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