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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 28 November 2025.
CLAIMS UNDER EXAMINATION
Claims 1-14 and 17-20 have been examined on their merits.
PRIORITY
The Applicant claims priority to EP19219342.3, filed on 23 December 2019.
WITHDRAWN REJECTIONS
The rejection of claims 1-14 and 17-20 on the ground of non-statutory obviousness-type double patenting is withdrawn in light of Applicant’s arguments.
MAINTAINED REJECTIONS
No arguments have been made directed to the rejections made under 35 USC 102 or 103. The rejections are maintained.
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.
Claims 11-19 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.
Claims 11 and 19 recite “the PCBMC cell culture”. It Is unclear if the claims are referring to the PBMC cell culture recited in the base claim. Appropriate correction is required.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 28 November 2025 are acknowledged. Argument 1: The Applicant states the claims have been amended to overcome the rejections.
Response to Argument 1:Claims 11 and 19 still recite “the PCBMC”. The rejection is maintained.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5, 8-9, 11, 13 and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Simader et al. (Safety and tolerability of topically administered autologous, apoptotic PBMC secretome (APOSEC) in dermal wounds: a randomized Phase 1 trial (MARSYAS I). Sci Rep 7, 6216 (2017).
Simader et al. evaluate the safety of two different doses of topically administered autologous APOSEC, the secretome of apoptotic peripheral blood mononuclear cells (PBMCs), in healthy male volunteers (hence, humans) with artificial dermal wounds (Abstract). Simader induces apoptosis of PBMCs from whole blood via ionizing irradiation (see text of Figure 2). The art teaches ionizing radiation increases the secretory output of PBMCs (last sentence of first paragraph on page 2). The art teaches irradiation with 60 Gy following collection of blood cells, before culture in CellGro medium (see page 4, “Production of APOSEC and placebo). Therefore the art is interpreted to teach irradiation before cultivation. Because the art anticipates the claimed method step, it would inherently prevent an allergy or allergic reaction as recited in claim 1.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004).
Therefore claim 1 is anticipated.
Because the method is anticipated, it would prevent a reaction caused by the allergens recited in claims 2-3.
Simader obtains PBMCs from blood. As evidenced by the specification ([0031] of PGPub), monocytes, T cells, B cells and NK cells are present in peripheral blood. Therefore claim 4 is included in this rejection.
Simader teaches Cellgro medium (supra). Therefore claim 5 is rejected.
Simader teaches 60 Gy ionizing radiation (supra). Therefore claim 8 and 17 are rejected.
The art teaches culture in CellGro medium for 24 hours (see page 4, “Production of APOSEC and placebo). Therefore claims 9 and 18 are rejected.
A sample was drawn for complete blood count to adjust white blood cells to a concentration of 25×106 cells/ ml, irradiated and cultured (see page 4, “Production of APOSEC and placebo).Therefore claims 11 and 19 are included in this rejection.
Simader teaches topical administration (see last paragraph of page 3). Therefore claim 13 is rejected.
Therefore Applicant’s Invention is anticipated as claimed.
Claims 1-5, 8-9, 11, 13 and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ankersmit et al. (Pharmaceutical preparation comprising supernatant of blood mononuclear cell culture. US2012/0045418 2012) as evidenced by Radiation Effect Research Foundation.
Ankersmit et al. administer irradiated culture supernatants of PBMCs to a mouse (a mammal) ([0075]). PBMC were irradiated with 60 Gy ([0079]). As evidenced by Radiation Effect Research Foundation, the gray (symbol: Gy) is the unit of ionizing radiation (first paragraph).
Because the art anticipates the claimed method step, it would inherently prevent an allergy or allergic reaction as recited in claim 1.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004).
Therefore claim 1 is anticipated.
Because the method is anticipated, it would prevent a reaction caused by the allergens recited in claims 2-3.
Ankersmit teaches the PBMCs are the subset of peripheral blood mononuclear cells (PBMCs) is preferably T cells, B cells or NK cells. Of course it is also possible to use combinations of these cells: T cells and B cells; T cells and NK cells; B cells and NK cells; T cells, B cells and NK cells. Methods for providing and isolating said cells are known ([0028]). Therefore claim 4 is included in this rejection. Ultra Culture Medium ([0030]) reads on claim 5. Irradiation with 60 Gy (supra) reads on claims 8 and 17.
Ankersmit teaches the PBMCs or a subset thereof are cultivated in a medium for at least 4 h, preferably for at least 6 h, more preferably for at least 12 h ([0036]). Therefore claims 9 and 18 are included in this rejection.
Supernatant is prepared from cells cultured at a density of 2.5×106 cells/ml ([0079]).
The disclosed amount of cells reads on claims 11 and 19.
The pharmaceutical preparation according to the present invention is topically administered ([0037]). Therefore claim 13 is rejected.
Therefore Applicant’s invention is anticipated as claimed.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Simader et al.
Claim 1 is anticipated by Simader et al. on the grounds set forth above. The teachings of Simader are reiterated. Simader teaches the supernatant (APOSEC) contains a myriad of cytokines, lipids, proteins and vasoactive substances that are used to heal wounds (see page 2, second paragraph). Simader treats humans. The volunteers were randomized into two groups: a low-dose group (A) receiving the supernatant of 12.5×106 PBMCs and a high-dose group (B) receiving an equivalent of 25×106 PBMCs per ml (Abstract; see first paragraph of Materials and Methods). Subjects are treated with approximately 1 ml APOSEC (see page 3, last paragraph). Simader teaches adequate production of APOSEC is defined by appropriate secretion of the following cytokines: interleukin (IL)-8 (0–5214pg/ml), epidermal growth factor (EGF; 25–226pg/ml), and transforming growth factor-β (TGF-β; 2575–21732pg/ml) (see page 4, first paragraph of section titled “Production of APOSEC and placebo”).
Simader is silent regarding the amount of APOSEC supernatant per kg of the human treated.
It would have been obvious to optimize the dose of supernatant administered. One would do so to treat the wound with the desired amount of cytokines, lipids, proteins and vasoactive substances Simader teaches are present in PBMC supernatant. MPEP 2144.05 teaches differences will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Therefore claims 12 and 20 are rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Ankersmit et al.
Claim 1 is rejected on the grounds set forth above. The teachings of Ankersmit are reiterated. Ankersmit teaches the composition can be used subjected to a combination of stress inducing conditions (see [0048]). Additional stress to the cells of the present invention leads to a further increase of the expression and secretion of substances beneficial for treating inflammatory skin conditions, in particular skin conditions associated with ischemia (see [0033]).
While the art teaches further stress inducing conditions.The art does not do so with sufficient specificity to anticipate the claims.
It would have been obvious to subject the PBMCs to a further stress inducing condition before or during cultivation. One would do so since Ankersmit teaches applying additional stress to the cells leads to a further increase of the expression and secretion of therapeutic substances. The skilled artisan would apply stress in addition to irradiation to increase the amount of therapeutic substances in the supernatant. One would have had a reasonable expectation of success since Ankersmit teaches PBMCs can be subjected to a combination of stress inducing conditions. Therefore claim 6 is rendered obvious. Ankersmit teaches include hypoxia, ozone, heat, radiation, chemicals, osmotic pressure and pH shift ([0048]). Therefore claim 7 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Ankersmit et al. in view of Usatine et al. (Diagnosis and Management of Contact Dermatitis. Am Fam Physician. 2010 Aug 1;82(3):249-55).
Claim 1 is rejected on the grounds set forth above. The teachings of Ankersmit are reiterated. Ankersmit teaches the composition can be used to treat contact dermatitis ([0026]). The art does not explicitly teach applying the composition after exposure to an allergen.
Usatine teaches contact dermatitis can be caused by an allergic reaction to a foreign substance contacting the skin (Abstract; first paragraph). Common substances that cause contact dermatitis include poison ivy, nickel and fragrances (page 2, left column, second paragraph).
It would have been obvious to administer the supernatant taught by Ankersmit following exposure to an allergen. Ankersmit teaches the composition can be used to treat contact dermatitis and Usatine teaches contact dermatitis is caused by exposure to an allergen. The skilled artisan would administer the supernatant following onset of the reaction. One would have had a reasonable expectation of success since Ankersmit teaches the composition can be used to treat a condition caused by an allergic reaction. Therefore claim 10 is rejected.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 14 is rejected over Ankersmit et al. in view of Powell Veterinary Science (Is Atopic Dermatitis Making Your Dog Miserable? 2017, pages 1-4).
Claim 1 is rejected on the grounds set forth above. The teachings of Ankersmit are reiterated. Ankersmit treats a human or animal ([0021]). Ankersmit teaches the composition can be used to treat atopic skin disease ([0026]). The art is silent regarding treating a dog.
Powell Veterinary Science teaches atopic dermatitis, or atopy, is a chronic, inflammatory skin condition that affects nearly 10% of dogs in the U.S. (first paragraph of page 1). Atopy is caused by an allergic reaction to substances in the environment and defects in the outer layer of skin. These substances, called allergens, include airborne pollens such as trees, grasses, weeds, and fungal spores (see second paragraph).
It would have been obvious to administer the supernatant taught by Ankersmit to treat a dog. One would have been motivated to do so since Ankersmit teaches the composition can be used to treat atopic skin diseases and Powell Veterinary Science teaches atopic skin diseases effect dogs. The skilled artisan would use a composition known to treat atopy in animals to treat atopy in a dog. One would have had a reasonable expectation of success since Ankersmit teaches the composition can be used to treat animals. Therefore claim 14 is rejected.
Therefore Applicant’s Invention is rendered obvious as claimed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653