DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Reply
Applicant's reply filed 5/01/2026 has been entered. The claims were not amended. Claims 1-15 remain pending, and are subject to the election requirement dated 2/04/2026.
Election/Restriction
Applicant’s election without traverse of claims 1-11 in the reply filed on 5/01/2026 is acknowledged. Applicant’s arguments are persuasive in-part to the extent that claim 14 was improperly and inadvertently grouped with the device claims, and so claim 14 is rejoined. However, Applicant’s characterization of claim 14 as a method claim depending from claim 1 is factually incorrect. Claim 14 is a product-by-process claim which incorporates the method steps of claim 1, see M.P.E.P. § 2113.
Claims 12, 13, and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/01/2026.
Claims 1-11 and 14 are under consideration on the merits.
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.
Claims 4 and 14 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.
The phrase "in particular” in claim 4 and “such as” in claim 14 renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. “In particular” raises similar issues of indefiniteness as other exemplary phrases “for example”, “or the like”, and “such as” as set forth in MPEP § 2173.05(d). Correction required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 14 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Claim 14 is a product-by-process claim and which recites a natural product, mononuclear cells (i.e. peripheral blood mononuclear cells) capable of undergoing apoptosis and capable of treating diseases of the immune system. At this time, there is no evidence of record that the claimed cells possess any markedly different characteristic imparted by the product-by-process limitations as compared to their nearest natural counterpart. See M.P.E.P. § 2106.04(c)(I). Mononuclear cells capable of undergoing apoptosis are known in this art as taught by Glisic-Milosavljevic et al. (Cell Prolif. 2005, 38, 301–311; Reference U) (see the Abstract), and are known as being capable of treating diseases of the immune system such as graft-versus-host disease (i.e. GvHD) as taught by Raiola et al. (Bone Marrow Transplantation (2003), 31, 687-693; Reference V) (see the Abstract, i.e. DLI or donor lymphocyte infusions).
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 1-4, 6-8, 11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Tuchinda et al. (Photodermatol Photoimmunal Photomed (2007), 23:2-9. pgs. 2-9; provided in the IDS dated 12/08/2023) in view of Mevorach et al. (WO 2016/170541; provided in the IDS dated 6/20/2023) in view of O’Neil (“Blood Components”, webpage (2013); Reference W).
Tuchinda teaches a method of producing apoptotic mononuclear cells, the method comprising: 1) obtaining human peripheral blood mononuclear cells from healthy volunteers (i.e. PBMCs) and separating the PBMCs from red blood cells by centrifugation (page 3, the 1st two paragraphs under “Materials and methods”), 2) subjecting the isolated PBMCs to ultraviolet radiation at wavelengths between 250 and 400 nm and with a peak emission at 313 nm (i.e. the FS40 UV lamp, see the paragraph spanning p3-4) to induce apoptosis in cells (as measured by caspase detection) greater than 15% at 24 hours post-irradiation (Fig. 1), reading on claims 1, 2, 4, and 14. Tuchinda teaches lysing the red blood cells in red blood cell lysis buffer comprising NH4Cl and KHCO3 (“page 3, subheading “Cell culture and isolation), reading on the embodiment of 100% mononuclear cells for claim 6 and reading on claim 7, and reading on the embodiment of 0% hematocrit for claim 8 (because the red blood cells are lysed). Tuchinda does not teach adding any photoactive- or apoptosis-inducing agent to the isolated PBMCs (see “Materials and methods” on pages 3-4), reading on the negative limitation of claim 11.
Regarding claim 3, Tuchinda is silent wherein the irradiation is arranged to further induce a rate of inhibition of cell proliferation greater than 70%, three days after irradiation. However, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure; see M.P.E.P. § 2111.02 and 2112.04. In this case, the wherein clause of claim 3 only expresses the intended result of the process step positively recited of claim 1 and so is afforded no (patentable) weight. Tuchinda is reasonably presumed capable of meeting the wherein clause of claim 3 absent any showing to the contrary.
Regarding claims 1 and 14, Tuchinda does not teach a peripheral blood fraction having a plasma content on 30-50%.
O’Neil teaches that the plasma/serum fraction of blood is about 55%. (2nd page, 1st paragraph under “Plasma), reading in-part on the peripheral blood fraction having a plasma content range of claims 1 and 14.
Regarding claims 1 and 14, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of Amer. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985). In this case, Tuchinda teaches obtaining the PBMCs from healthy human subjects and O’Neil teaches that the plasma/serum fraction of blood is about 55%. Therefore, the claimed plasma content ranges must be held prima facie obvious over Tuchinda in view of O’Neil as there is a reasonable presumption that plasma content of Tuchinda is close enough to the claimed range that one skilled in the art would have expected them to have the same properties and absent any showing to the contrary.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Tuchinda and O’Neil as applied to claim 1 above, and further in view of Mevorach (WO 2016/170541; provided in the IDS dated 6/20/2023).
The teachings of Tuchinda and O’Neil are relied upon as set forth above.
Regarding claim 5, Tuchinda and O’Neil do not teach wherein the peripheral blood fraction is obtained by leukapheresis or by isolating the buffy coat from a whole blood sample. Regarding claim 9, Tuchinda and O’Neil do not teach wherein the peripheral blood fraction has a volume of between 6 ml and 200 ml.
Mevorach teaches methods of preparing mononuclear apoptotic cells and compositions thereof (Abstract). Mevorach teaches irradiating mononuclear-enriched cell populations with gamma or UV (ultraviolet) radiation (¶0014), reading on claims 5 and 9. Mevorach teaches obtaining said mononuclear-enriched cell populations comprises obtaining white blood cell (WBC) fractions from multiple individual donors by leukapheresis (¶0017), reading on claim 5. Mevorach teaches resuspending the pooled mononuclear-enriched cell composition in an administration medium having a volume between 100-1000 ml or 200-800 ml to produce a pharmaceutical composition thereof (¶0169) for administration to subjects in need thereof (¶0035), reading on claim 9.
Regarding claim 5, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the leukapheresis step of Mevorach to the methods of Tuchinda. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Mevorach and Tuchinda are directed towards methods of making apoptotic mononuclear cells by irradiation. The skilled artisan would have been motivated to do so because Mevorach teaches that the addition would be predictably advantageous to obtain white blood cell fractions from multiple individual donors and so would improve upon Tuchinda’s methods.
Regarding claim 9, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further resuspend the peripheral blood fraction of Tuchinda in a volume of 100-200ml in view of Mevorach. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Mevorach and Tuchinda are directed towards methods of making apoptotic mononuclear cells by irradiation. The skilled artisan would have been motivated to do so because the addition would be predictably advantageous to further formulate the apoptotic mononuclear cells of Tuchinda for administration to subjects in need thereof as taught by Mevorach.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Tuchinda and O’Neil as applied to claim 1 above, and further in view of Kim et al. (Photochem Photobiol. 2018 July ; 94(4), 17 page author manuscript; Reference X).
The teachings of Tuchinda and O’Neil are relied upon as set forth above.
Regarding claim 10, Tuchinda and O’Neil do not teach wherein the peripheral blood fraction containing the mononuclear cells is agitated during irradiation.
Kim teaches methods of inactivating bacteria in whole blood, the method comprising agitating/pumping whole blood in a device and irradiating the whole blood with UV-C light (Abstract; Figure 1; page 5, subheading “UV-C exposure of tube”) and effective to reduce S. aureus to 43.1% of its original CFU/ml and to reduce MRSA to 2.6% of its original CFU/ml in the whole blood (Figure 3), reading on claim 10.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the irradiating and pumping/agitating device of Kim to the methods of Tuchinda. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Kim and Tuchinda are in-part towards blood compositions and irradiating said compositions with UV light. The skilled artisan would have been motivated to do so because Kim teaches that the addition would be predictably advantageous to inactive or reduce the concentration of bacteria that might be in the starting whole blood of Tuchinda.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 14 is rejected under 35 U.S.C. 102 (a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Glisic-Milosavljevic et al. (Cell Prolif. 2005, 38, 301–311; Reference U) as evidenced by Raiola et al. (Bone Marrow Transplantation (2003), 31, 687-693; Reference V).
Glisic-Milosavljevic teaches a composition comprising mononuclear cells obtained from healthy donors and being inherently capable of undergoing apoptosis and when stimulated in vitro for 3 days or 5 days with the combination of PMA and ionomycin or when stimulated for 5 days in vitro with IL2 (pages 303, paragraph starting “Peripheral blood…” through the next paragraph ending “…was also measured.”; Figure 3, and page 305 the paragraph starting “Applied stimulation…” through the next paragraph ending “…as a reference.” on page 306), and are known as being capable of treating diseases of the immune system such as graft-versus-host disease (i.e. GvHD) as evidenced by Raiola (see the Abstract, i.e. DLI or donor lymphocyte infusions).
Claim 14 is product-by-process claim. See M.P.E.P. § 2113; product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. Furthermore, alternate grounds of rejection under both 102 and 103 is permissible given the lack of physical description of product-by-process claims and the inability of the USPTO to manufacture and compare products. See M.P.E.P. § 2113 (III). Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference. In this case, the burden is shifted to Applicant to show that the manufacturing process steps of the product-by-process claims impart any novel and/or non-obvious structural characteristics to the claimed product as compared to the substantially identical mononuclear cell composition taught by Glisic-Milosavljevic evidenced by Raiola. Glisic-Milosavljevic teaches that being inherently capable of undergoing apoptosis or when stimulated in vitro with IL2 and the combination of PMA and ionomycin, and the evidentiary teachings or Raiola make clear that mononuclear cells are capable of treating diseases of the immune system such as graft-versus-host disease. Particularly, if the product-by process limitations of claim 14 impart no structural difference then the claim is anticipated. If the product-by process limitations of claim 14 imparts a structural difference, then Applicant must clearly set forth why any structural difference between the claimed composition and the substantially identical mononuclear cell composition of Glisic-Milosavljevic evidenced by Raiola is non-obvious.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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