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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/26/2025 has been entered.
Response to Amendments
Applicant's amendments filed 6/26/2025 to claims 1 and 4 have been entered. Claims 3, 6-8, and 16 are canceled. Claims 1, 2, 4, 5, 9-15, and 17-24 remain pending, of which claims 1, 2, 4, 5, and 9 are being considered on their merits. Claims 9-15 and 17-24 remain withdrawn from consideration. References not included with this Office action can be found in a prior action.
Applicant’s arguments over Weirich on pages 7-8 of the reply are persuasive, and the alternative 35 U.S.C. § 102 and 103 rejections of record are withdrawn.
Any other rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Affidavit/Declaration
The Declaration under 37 CFR 1.132 filed 6/25/2025 is insufficient to overcome the 35 U.S.C. § 101 and alternate 35 U.S.C. § 102 and 103 rejections as set forth in the last Office action for the reasons given below. Any remarks over Weirich are moot as Weirich is no longer applied against the claims at this time.
On pages 2-4 and again on page 5 of the Declaration, Declarant alleges that Forsberg as evidenced by Wang is deficient by not teaching surface expression of CD62L. This is not found persuasive because 1) the burden of proof for patent eligibility rejections under 35 U.S.C. § 101 is to show a markedly different characteristic of the claimed product as compared to the nature based product or recite a limitation that amounts to “significantly more”, and 2) the burden of proof for alternate rejections under 35 U.S.C. § 102 and 103 is “substantially identical,”, which shifts the burden to Applicant that prior art composition/product to show by a preponderance of evidence that the claimed product is not identical to the claimed composition/product, see M.P.E.P. § 2112.01. For 35 U.S.C. § 101, at this time Declarant did not provide any factual evidence that the claimed neutrophil composition possesses a markedly different characteristic of the claimed product as compared to the nature based product nor were the claims otherwise amended to recite a limitation that amounts to “significantly more”. For the alternate 35 U.S.C. § 102 and 103 rejections of record, Declarant has not yet presented any evidence that Forsberg does not possess the cell marker expression pattern of claim 1; see M.P.E.P. § 2121 (I).
On page 6 of the Declaration, Declarant alleges that Walsh is deficient by not teaching the product-by-process limitations of 4-phenylbutyrate (4-PBA) and G-CSF for claims 4 and 5. This is not persuasive because patentability is based upon the product itself. See M.P.E.P. § 2113. In this case, Declarant has not yet shown by any preponderance of evidence that the product-by-process limitations of claims 4-5 impart any structural difference to the claimed neutrophils as compared to Walsh. Nor has Declarant shown by any preponderance of evidence that the neutrophil composition of Walsh does not possess the cell marker expression pattern of claim 1; see M.P.E.P. § 2121 (I). The instant amendments adding the product-by-process limitation towards G-CSF is fully addressed by the addition of Wolach below.
On pages 6-7 of the Declaration, Declarant alleges that Walsh is deficient because the neutrophils of Walsh loaded with 4-phenylbutyrate (4-PBA) only then release 4-PBA in a range of 9-18 µM. This is not found persuasive because Declarant is alleging error over unclaimed features; although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In this case, claims 4-5 do not require any product-by-process limitations towards cellular release of 4-PBA only towards contacting the neutrophils with 4-PBA which is plainly met by Walsh as was and remains cited in the 35 U.S.C. § 101 rejection of record.
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.
Claims 1, 2, 4, 5, and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claim 1 recites a natural product comprising chemically programmed neutrophil having increased surface expression of CD62L as compared to a control, decreased gene and/or protein expression of CD11b, MMP-9, LTB4, MPO, and/or Dectin-1 as compared to the control, increased gene and/or protein expression of FPN, TGF, and/or LRRC32 as compared to the control, decreased activity of ox CAMKII as compared to the control, or any combination thereof, wherein the control is a neutrophil or population thereof having non-resolving inflammation phenotype.
Regarding claims 1, 4, and 5, at this time there is no evidence that the cells of claim 1 possess or the product-by-process limitations of claims 1, 4, and 5 impart any markedly different characteristic as compared to the nearest natural counterpart. Gene and/or protein expression of cellular markers is not static, and is known in this art to changeable by natural processes. For example, White-Owen (J Surg Res. (1992), 52(1), 22-26; Reference U) teaches decreased expression of CD11b in response to traumatic injury in peripheral blood neutrophils (see the Abstract). Ekpenyong (Biochimica et Biophysica Acta 1853 (2015) 3105–3116) teaches that neutrophils endogenously switch between the activated/primed state and subsequent deactivated/deprimed state in response to respond to natural stimuli such that these cells and perform their antibacterial, pro-, and anti-inflammatory functions (2nd paragraph under the Introduction). Ekpenyong teaches that neutrophils respond to endogenous mechanical stress to switch between the activated and resting/deactivated state through a CD11b and CD18 mechanism (Fig. 3). Malcolm (Am J Physiol Lung Cell Mol Physiol (2003), 284: L663–L670) teaches neutrophils respond to infection by degranulation, release of reactive oxygen intermediates, secretion of chemokines and cytokines (Abstract), and change gene expression patterns as measured by microarray on LPS-treated neutrophils (with LPS being a component of gram-negative bacteria and found at the site of infection) (Abstract and the 1st two paragraphs under the Abstract; Table 1). Finally, Pillay (J Clin Invest. 2012;122(1):327-336; Reference V) teaches an ex vivo or in vitro chemically programed neutrophil cell population, the cells being obtained from subjects treated with LPS/endotoxin and comprising increased CD62L expression at 180 and 360 minutes post-LPS expression relative to a control group of neutrophils at 0 minutes post LPS administration (Fig. 1C, e.g. an increase in total neutrophils expressing CD62L) and wherein the CD62L is detected by (in vitro) staining (p334, 1st paragraph under “Methods” and the last paragraph of the “Introduction” on p327) and Soler-Rodriguez (J Immunol. (2000), 164, 2674-2683; Reference W) teaches that LPS (endotoxin) naturally activates neutrophils during bacterial infection (paragraph starting “Neutrophils have been shown…”).
The totality of the evidence at this time does yet not suggest any markedly different characteristic between the cells of claim 1 and the cells made by the product-by-process limitations of claims 1, 4, and 5 and their nearest natural counterpart.
Regarding claim 1, the judicial exception is not integrated into a practical application and does not amount to significantly more because this claim is only directed towards the natural product itself and there no evidence as yet of record that the claimed cells possess any markedly different characteristic compared to the nearest natural counterpart.
Regarding claim 2, the embodiment of a generic exogenous gene does not amount to significantly more because no specific structure and/or function is claimed and so generally linking the use of the judicial exception to a particular technological environment or field of use.
Regarding claims the ex vivo or in vitro cells of claim 1, and claims 4, 5, and 9, these claims do not recite any elements that amount to significantly more than the judicial exception because these limitations are routine and conventional over Walsh (US 6,207,195) and Wolach (Experimental Hematology 35 (2007) 541–550; Reference X). Wolach teaches that contacting neutrophils in vitro with granulocyte colony-stimulating factor (G-CSF) was routine and conventional to increase the number of viable neutrophils (Abstract; Fig. 1, middle panel). Walsh teaches a composition comprising gelatin nanospheres comprising 0.1-0.4% w/v 4-phenylbutyrate (4-PBA)(Example 1). Walsh teaches methods of transfecting cells with the 4-PBA-loaded nanospheres into human bronchial epithelial cells (Col. 7, lines 45-63 in Example 2), and envisions transfecting neutrophils as an alternative to epithelial cells (Col. 5, lines 36-48), reading on claim 1 and the product-by-process limitations of claims 4 and 7, and the embodiment of transfection medium or culture medium for the pharmaceutically acceptable carrier of claim 9. Walsh teaches that loading cells with 4-phenylbutyrate would be predictably advantageous to induce gene transcription in cells of interest and remediate defective protein localization intracellularly (Abstract), reading on claim 1.
The 0.4% w/v 4-phenylbutyrate concentration of Walsh reads on the concentration range of claim 5 based on the following calculations:
4-phenylbutyrate (PubChem CID: 22053264) has a molecular weight of 163.19 g/mol,
%Weight-by-volume equates to grams per 100 ml,
For 0.1% w/v: (0.1 g ÷ 100 ml) * (1000 mg ÷ 1 g) = 1 mg/ml
1 mg/ml * (1000 ml/L) * (1 g/1000 mg) * (1 mol ÷ 163.19 g) = 0.00612 g/L = 6.12 mM
For 0.4% w/v: (0.4 g ÷ 100 ml) * (1000 mg ÷ 1 g) = 4 mg/ml
4 mg/ml * (1000 ml/L) * (1 g/1000 mg) * (1 mol ÷ 163.19 g) = 0.0245 g/L = 24.5 mM
For the reasons given above, claims 1, 2, 4, 5, 7, and 9 are rejected under 35 U.S.C. § 101 as being directed towards a judicial exception without significantly more.
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, and 5 are 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 Forsberg et al. (US 8,142,798) as evidenced by Yang et al. (PLoS One (2011), 6(7), e22560).
Forsberg teaches a chemically programmed neutrophil comprising increased protein expression of L-selectin (i.e. CD62L) in sheep fed a nutritional composition as compared to control animals (Example 1 and Fig. 1 for protein expression as measured by Western blot).
Regarding claim 1, Forsberg does not teach any increase in cell surface expression of CD62L/L-selectin. However, Yang teaches that CD62L is cell adhesion molecule (e.g. expressed on the surface of the cell membrane) found in neutrophils (1st paragraph of the Introduction). While Forsberg’s Western blotting methods are plainly understood to involve a step of cell lysis, the increased CD62L/L-selectin protein expression taught by Forsberg is reasonably construed as being an increase in the surface expression of CD62L/L-selectin when the neutrophils are intact as this protein is inherently found on the surface of the cells as evidenced by Yang. Therefore, Forsberg as evidenced by Yang anticipates or reads on the embodiment of increased surface expression of CD62L/L-selectin as compared to a control for claim 1.
Regarding the wherein clause of claim 1, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." Also, alternate rejections under both 102 and 103 are appropriate when Applicant claims a composition in terms of a function or property and the composition of the prior art is the same as that of the claim but does not explicitly disclose the function or property. See M.P.E.P. § 2112; once a substantially identical product/composition has cited and a rationale tending to show inherency is set forth, the burden shifts to Applicant to overcome the 102 rejection by showing the prior art product lacks the claimed function/property, and to overcome the 103 rejection by further showing that any different in the claimed function/property is non-obvious.
In this case, the function/property is an increase in the protein expression of CD62L/L-selectin relative to a control population of neutrophils having a non-resolving inflammation phenotype. The prior art neutrophils of Forsberg as evidenced by Yang are substantially similar to the claimed neutrophils because they show increased expression of CD62L/L-selectin relative to a control population of untreated neutrophils in animals fed a different diet. Therefore, the burden to establish both novelty and non-obviousness over Forsberg as evidenced by Yang is shifted back to Applicant.
Claim 1 recites product-by-process limitations towards ex vivo or in vitro neutrophils. Claims 4 and 5 are product-by-process claims. 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 composition taught by Forsberg as evidenced by Yang, who teaches a substantially identical chemically programmed neutrophil population having increased surface expression of CD62L/L-selectin. Particularly, if the product-by process limitations of claims 1, 4, and 5 impart no structural difference then the claims are anticipated. If the product-by process limitations of claims 1, 4, and 5 impart a structural difference, then Applicant must clearly set forth why any structural difference between the claimed composition and the composition of Forsberg as evidenced by Yang 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.
Claims 1, 4, 5, and 9 are 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 White-Owen et al. (J Surg Res. (1992), 52(1), 22-26; Reference U).
White-Owen teaches decreased expression of CD11b in response to traumatic injury in peripheral blood neutrophils (see the Abstract; p23, subheadings “Subjects,” “Blood Handling”, and “PMN Staining”), anticipating or reading on claim 1 and the embodiment of blood and/or water for the pharmaceutically acceptable carrier of claim 9.
Regarding the wherein clause of claim 1, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." Also, alternate rejections under both 102 and 103 are appropriate when Applicant claims a composition in terms of a function or property and the composition of the prior art is the same as that of the claim but does not explicitly disclose the function or property. See M.P.E.P. § 2112; once a substantially identical product/composition has cited and a rationale tending to show inherency is set forth, the burden shifts to Applicant to overcome the 102 rejection by showing the prior art product lacks the claimed function/property, and to overcome the 103 rejection by further showing that any different in the claimed function/property is non-obvious.
In this case, the function/property is an increase in the protein expression of CD62L/L-selectin relative to a control population of neutrophils having a non-resolving inflammation phenotype. The prior art neutrophils of White-Owen are substantially similar to the claimed neutrophils because they show decreased expression of CD11b relative to a control population of neutrophils obtained from uninfected subjects. Therefore, the burden to establish both novelty and non-obviousness over White-Owen is shifted back to Applicant.
Claim 1 recites product-by-process limitations towards ex vivo or in vitro neutrophils. Claims 4 and 5 are product-by-process claims. 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 composition taught by White-Owen, who teaches a substantially identical chemically programmed neutrophil population having decreased surface expression of CD11b. Particularly, if the product-by process limitations of claims 4, 5, and 7 impart no structural difference then the claims are anticipated. If the product-by process limitations of claims 2, 5, and 7 impart a structural difference, then Applicant must clearly set forth why any structural difference between the claimed composition and the composition of White-Owen 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.
Claims 1, 4, 5, and 9 are 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 Pillay et al. (J Clin Invest. 2012;122(1):327-336; Reference V).
Pillay teaches an ex vivo or in vitro chemically programed neutrophil cell population, the cells being obtained from subjects treated with LPS/endotoxin and comprising increased CD62L expression at 180 and 360 minutes post-LPS expression relative to a control group of neutrophils at 0 minutes post LPS administration (Fig. 1C, e.g. an increase in total neutrophils expressing CD62L) and wherein the CD62L is detected by (in vitro) staining (p334, 1st paragraph under “Methods” and the last paragraph of the “Introduction” on p327), anticipating or reading on claim 1 and the embodiment of blood and/or water for the pharmaceutically acceptable carrier of claim 9.
Regarding the wherein clause of claim 1, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." Also, alternate rejections under both 102 and 103 are appropriate when Applicant claims a composition in terms of a function or property and the composition of the prior art is the same as that of the claim but does not explicitly disclose the function or property. See M.P.E.P. § 2112; once a substantially identical product/composition has cited and a rationale tending to show inherency is set forth, the burden shifts to Applicant to overcome the 102 rejection by showing the prior art product lacks the claimed function/property, and to overcome the 103 rejection by further showing that any different in the claimed function/property is non-obvious.
In this case, the function/property is an increase in the protein expression of CD62L/L-selectin relative to a control population of neutrophils having a non-resolving inflammation phenotype. The prior art neutrophils of Pillay are substantially similar to the claimed neutrophils because they show increased CD62L expression relative to a control population of neutrophils post-LPS treatment. Therefore, the burden to establish both novelty and non-obviousness over Pillay is shifted back to Applicant.
Claim 1 recites product-by-process limitations towards ex vivo or in vitro neutrophils. Claims 4 and 5 are product-by-process claims. 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 composition taught by Pillay, who teaches a substantially identical chemically programmed neutrophil population having increased CD62L expression relative to a control population of neutrophils post-LPS treatment. Particularly, if the product-by process limitations of claims 1, 4, and 5 impart no structural difference then the claims are anticipated. If the product-by process limitations of claims 1, 4, and 5 impart a structural difference, then Applicant must clearly set forth why any structural difference between the claimed composition and the composition of White-Owen 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.
Claims 1, 2, 4, 5, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (US 6,207,195; provided in the IDS dated 6/28/2021) in view of Wolach (Experimental Hematology 35 (2007) 541–550; Reference X).
Walsh teaches a composition comprising gelatin nanospheres comprising 0.1-0.4% w/v 4-phenylbutyrate (4-PBA)(Example 1). Walsh teaches methods of transfecting cells with the 4-PBA-loaded nanospheres into human bronchial epithelial cells (Col. 7, lines 45-63 in Example 2), and envisions transfecting neutrophils as an alternative to epithelial cells (Col. 5, lines 36-48), reading on claim 1 and the product-by-process limitations of claims 1 and 4, and the embodiment of transfection medium or culture medium for the pharmaceutically acceptable carrier of claim 9. Walsh teaches loading the human bronchial cells with an exogenous reporter gene encoding for a green fluorescence protein to optically determine nanosphere uptake into the cells (Example 2), reading on the embodiment of a generic exogenous gene and the optional embodiment of GFP as a species of selectable marker for claim 2.
Walsh teaches that loading cells with 4-phenylbutyrate would be predictably advantageous to induce gene transcription in cells of interest and remediate defective protein localization intracellularly (Abstract), reading on claim 1.
The 0.4% w/v 4-phenylbutyrate concentration of Walsh reads on the concentration range of claim 5 based on the following calculations:
4-phenylbutyrate (PubChem CID: 22053264) has a molecular weight of 163.19 g/mol,
%Weight-by-volume equates to grams per 100 ml,
For 0.1% w/v: (0.1 g ÷ 100 ml) * (1000 mg ÷ 1 g) = 1 mg/ml
1 mg/ml * (1000 ml/L) * (1 g/1000 mg) * (1 mol ÷ 163.19 g) = 0.00612 g/L = 6.12 mM
For 0.4% w/v: (0.4 g ÷ 100 ml) * (1000 mg ÷ 1 g) = 4 mg/ml
4 mg/ml * (1000 ml/L) * (1 g/1000 mg) * (1 mol ÷ 163.19 g) = 0.0245 g/L = 24.5 mM
Regarding claim 1, Walsh does not teach a single embodiment comprising chemically programmed neutrophils. However, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the epithelial cells of Walsh with the neutrophils of Walsh in Walsh’s methods of transfecting cells with 4-phenylbutyrate. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Walsh expressly considers the combination. The skilled artisan would have been motivated to do so because Walsh expressly teaches that loading cells, such as neutrophils, with 4-phenylbutyrate would be predictably advantageous to induce gene transcription in cells of interest and remediate defective protein localization intracellularly.
Regarding the gene and/or protein expression patterns of claim 1, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not. See M.P.E.P. § 2112; once a substantially identical product/composition has cited and a rationale tending to show inherency is set forth, the burden shifts to Applicant to overcome the 103 rejection by further showing that any different in the claimed function/property is non-obvious.
In this case, the function/property is gene and/or protein expression patterns of claim 1. The prior art neutrophils transfected with 4-phenylbutyrate envisioned by Walsh is substantially similar to the claimed chemically programed neutrophils because they are made by a substantially identical process of treating the neutrophils with 4-phenylbutyrate and G-CSF. Therefore, the burden to show non-obviousness over Walsh is shifted back to Applicant.
Regarding claim 4, Walsh does not teach the product-by-process limitation of contacting neutrophils with G-CSF.
Wolach teaches that contacting neutrophils in vitro with granulocyte colony-stimulating factor (G-CSF) at 20 ng/ml increases the number of viable neutrophils (Abstract; Fig. 1, middle panel; ), reading on claim 4.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the G-CSF of Wolach to the methods and neutrophil composition of Walsh. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Wolach and Walsh are directed towards neutrophil compositions, and because Wolach teaches a specific G-CSF concentration. The skilled artisan would have been motivated to do so because Wolach teaches that contacting neutrophils in vitro with granulocyte colony-stimulating factor (G-CSF) at 20 ng/ml increases the number of viable neutrophils, and to the addition would predictably improve upon the methods and neutrophil composition of Walsh by yielding more viable neutrophils.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 6-18 of the reply have been fully considered, but not found persuasive of error for the reasons given below. Any reference to the instant Declaration is fully addressed above. Any arguments over Weirich is moot as Weirich is no longer applied
On pages 6-7 of reply, Applicant alleges that the claimed neutrophils possess markedly different characteristics from their (nearest) natural counterparts. This is not found persuasive of error because Applicant has not yet shown by a preponderance of evidence that naturally occurring neutrophils are not capable of the surface marker expression profile of claim 1, see M.P.E.P. § 2121 (I). Furthermore, see In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and M.P.E.P. § 2112.01: "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." (emphasis added). In this case, the cited art makes clear that cell surface marker expression in an inherent property of neutrophils and that neutrophils naturally express a subset of the claimed cell surface markers, thus appropriately shifting the burden to Applicant to demonstrate the claimed neutrophils possess any markedly different characteristic as compared to the nearest natural counterpart as the claims only recite a nature-based product, see M.P.E.P. § 2106.04(c).
Applicant’s arguments over Ekpenyong and Malcolm on page 8 of the reply and “counterpart analysis” arguments on page 9 of the reply are not persuasive because Applicant appears to conflate the patent eligibility analysis under 35 U.S.C. § 101 to require anticipatory prior art as would be applied under 35 U.S.C. § 102. See the preceding paragraph, in so much as the burden remains with Applicant to show by a preponderance of evidence to show the claimed neutrophils ( a nature-based product) possess any markedly different characteristic as compared to the nearest natural counterpart or to otherwise amend the claims to obviate the 35 U.S.C. § 101 rejection of record.
Applicant’s arguments over the product-by-process limitations of claims 4 and 5 on page 9 of the reply are not found persuasive because, again, Applicant has not yet shown by a preponderance of evidence that the product-by-process claims impart any markedly different characteristic as compared to the nearest natural counterpart, see M.P.E.P. § 2106.04(c)(I)(B).
On page 9 of the reply, Applicant alleges that the “pharmaceutical formulation” of claim 9 integrates the claim into a practical application. This is not found persuasive of error because claim 9 is generic and recites no additional specific structure and/or function and so is only generally linking the use of the judicial exception to a particular technological environment or field of use, and because Walsh teaches that formulating the claimed neutrophils in the embodiment of (aqueous) transfection medium or culture medium as a species of pharmaceutically acceptable carrier is routine and conventional in this art.
On pages 10-13 of the reply, Applicant traverses the alternate 102/103 rejections of claims 1, 4, and 5 over Forsberg as evidenced by Yang and claims 1, 4, 5 and 9 over Weirich. This is not found persuasive because the composition of Forsberg as evidenced by Yang remain substantially identical to the claimed composition, and the burden of proof remains with Applicant to show inoperability of the prior art with respect to the cell marker expression pattern of claim 1 or otherwise demonstrate novelty and nonobviousness.
On page 15 of the reply, Applicant traverses the 35 U.S.C. § 103 rejections of claims 1, 4, 5, and 9 over Walsh. This is not found persuasive because the composition of Walsh remains substantially identical to the claimed composition and produced by a substantially similar method by the addition of 4-phenylbutyrate (4-PBA), and the burden of proof remains with Applicant to show inoperability of the prior art with respect to the cell marker expression pattern of claim 1 or otherwise demonstrate novelty and nonobviousness. Claims 4-5 are product-by-process claims, and are only considered to the extent they impart a structural difference to the claimed cellular composition (see M.P.E.P. § 2113), and Applicant has not yet shown by any preponderance of evidence that the process steps of Walsh impart any novel or non-obvious structure to the claimed cells and Applicant has not shown by any preponderance of evidence that the neutrophils of Walsh are otherwise not capable of expressing the cell surface markers of claim 1 (see M.P.E.P. § 2121). The instant amendments adding the product-by-process limitation towards G-CSF is fully addressed by the addition of Wolach above.
On page 16 of the reply, Applicant alleges that the claimed 4-PBA concentration produces an unexpected result. This is not found persuasive because it relies on a faulty interpretation of the scope of the claim; although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In this case, claims 4-5 do not require any product-by-process limitations towards cellular release of 4-PBA only towards contacting the neutrophils with 4-PBA which is plainly met by Walsh as was and remains cited in the alternate 35 U.S.C. § 102 and 103 rejections of record. Applicant has still not yet shown by any preponderance of evidence that the process steps of Walsh impart any novel or non-obvious structure to the claimed cells and Applicant has not shown by any preponderance of evidence that the neutrophils of Walsh are otherwise not capable of expressing the cell surface markers of claim 1 (see M.P.E.P. § 2121).
Conclusion
No claims are allowed. No claims are free of the art.
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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