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 .
Priority
The instant application is a continuation-in-part of US Application No. 18/321738, filed 22 May 2023. Acknowledgement is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 63/344258, filed 20 May 2022.
Drawings
The replacement drawing sheets filed 06 February 2024 are acknowledged and entered into the application file.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the Specification filed 06 February 2024 contains amino acid sequences within Table 5 on Page 47.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the Specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). More specifically, as aforementioned the Specification filed 06 February 2024 contains amino acid sequences within Table 5 on Page 47 that do not comprise sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The abstract of the disclosure filed 22 November 2023 is objected to because it comprises grammatical errors. More specifically, the abstract recites “a method of generating, ex vivo production of soluble Lox-1, comprising…” instead of “a method of producing soluble Lox-1 ex vivo, comprising…”, or the like.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
In addition, the substitute Specification filed 06 February 2024 is acknowledged and entered into the application file.
With that, the Specification filed 06 February 2024 is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pages 51, 53, and 55 within references 18, 46, 57, and 61. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 1-3, 5-7, 11-12, 14, 16, 19, and 22 are objected to because of the following informalities:
Regarding claim 1: The instant claim is objected to for reciting “[a] method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising…” instead of “[a] method ofthe ex vivo production of soluble Lox-1 (sLox-1), comprising…” or “[a] method of producing soluble Lox-1 (sLox-1) ex vivo, comprising…”, or the like.
The instant claim is further objected to for comprising language that does not amount to a 35 USC 112(b) rejection or an interpretation under 35 USC 112(f), but is not entirely clear. The Examiner provides an interpretation below.
Appropriate correction is required.
Regarding claims 2-3, 5-6, 12, 14, 19, and 22: The instant claims are each objected to for comprising language that does not amount to a 35 USC 112(b) rejection or an interpretation under 35 USC 112(f), but is not entirely clear. The Examiner provides an interpretation below.
Appropriate correction is required.
Regarding claim 7: The instant claim is objected to for failing to recite “wherein” prior to the recitation of “the device” in Line 1.
Appropriate correction is required.
Regarding claim 11: The instant claim is objected to for reciting “Myeloid-derived” instead of “myeloid-derived” within Line 2.
The instant claim is further objected to for comprising language that does not amount to a 35 USC 112(b) rejection or an interpretation under 35 USC 112(f), but is not entirely clear. The Examiner provides an interpretation below.
Appropriate correction is required.
Regarding claim 16: The instant claim is objected to for failing to recite “the” prior to the recitation of “one or more interleukins and/or cytokines” in Line 1.
Appropriate correction is required.
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 2 and 11-13 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.
Regarding claim 2: The instant claim recites the limitation, “wherein an additional enhancing material… configured to modulate sLox-1 is added to the cultured blood clot.” The scope of the instant claim is unclear, as the ordinary artisan cannot readily determine the metes and bounds of how the enhancing material “modulates” sLox-1. Therefore, the scope of the claim is rendered indefinite.
Appropriate correction is required.
Regarding claim 11: The instant claim recites the limitation, “wherein the neutrophils are configured to undergo … PMN-MDSC polarization”. The scope of the instant claim is unclear, as the ordinary artisan cannot readily determine if the PMN-MDSC polarization is an inherent action of the neutrophils, or is instead a required active step of the method. Therefore, the scope of the claim is rendered indefinite.
Appropriate correction is required.
Regarding claims 12-13: Instant claim 12 recites the limitation, “wherein a cultured clot serum…is configured to provide an endothelial barrier-enhancing effect…”. The scope of the instant claim is unclear, as the ordinary artisan cannot readily determine the metes and bounds of the “barrier-enhancing effect” of the cultured clot serum. Therefore, the scope of the claim is rendered indefinite.
Instant claim 13 is included in the rejection since it depends from rejected claim 12.
Appropriate correction is required.
Claim Interpretation
The claims appear to be English translations which have resulted in grammatical errors or inconsistencies, resulting in objections and/or 112b rejections. The Examiner has attempted to interpret the claims to be consistent with the content of the claims and/or the Specification. In order to advance prosecution, claims 1-3, 5-6, 11-12, 14, 19, and 22 are interpreted as reciting the following:
Regarding claim 1: A method of producing soluble Lox-1 (sLox-1) ex vivo, comprising:
introducing a blood sample into a device, wherein the blood sample comprises neutrophils;
adding a coagulation enhancing material to the blood sample to form a cultured blood clot;
incubating the cultured blood clot in the device at a temperature greater than 25°C and less than 45°C for at least 2 hours to allow the neutrophils comprised within the blood sample to produce Lox-1 and then to shed the sLox-1 outside the cultured blood clot; and
collecting the sLox-1 that has been shed in the device, wherein the amount of shed sLox-1 in the device is more than the amount of sLox-1 in a fresh blood sample.
Regarding claim 2: The method of claim 1, wherein an additional enhancing material is added to the cultured blood clot, wherein the additional enhancing material comprises a lipopolysaccharide (LPS) or phorbol myristate acetate.
Regarding claim 3: The method of claim 1, wherein the cultured blood clot produces one or more interleukins and/or cytokines.
Regarding claim 5: The method of claim 1, wherein 0.2 ng to 50 ng of sLox-1 per mL of the blood sample is shed.
Regarding claim 6: The method of claim 1, wherein the sLox-1 is autologous sLox-1.
Regarding claim 11: The method of claim 1, wherein the neutrophils comprised within the blood sample undergo polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) polarization.
Regarding claim 12: The method of claim 1, wherein a cultured clot serum of the cultured blood clot provides an increased endothelial barrier-enhancing effect when compared to a clot serum from a fresh blood sample.
Regarding claim 14: The method of claim 1, wherein the method further comprises detecting a drug response within the blood sample.
Regarding claim 19: The method of claim 1, wherein the method further comprises estimating an amount of active alpha- 1 antitrypsin in the blood sample to detect a disease in a subject.
Regarding claim 22: The method of claim 14, wherein the method further comprises monitoring the sLox-1 production before and after a patient treatment or a clinical trial, wherein the patient is treated with a therapy that influences neutrophil or platelet counts.
It is noted that Applicant is not required to amend the claims as interpreted above, and the interpretations represent only one way to accomplish what the Examiner believes Applicant was attempting to originally convey. Applicant is only required to amend the claims in order to render the claims to correct errors and/or inconsistencies sufficiently to overcome the objections and 35 USC 112(b) rejections above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-8, 10-11, 14-18, 20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Patzke (US 2023/0280359 A1) in view of Tolle et al (Int J Mol Sci, 2021) and Condamine et al (Sci Immunol, 2017).
Patzke is considered prior art under 35 USC 102(a)(2), with an effective filing date of 03 March 2022. Tolle et al and Condamine et al are each considered prior art under 35 USC 102(a)(1).
Regarding claims 1, 7-8, 10, and 20: Patzke discloses test methods for establishing an individual’s blood coagulation system status and providing information of the functionality of the blood coagulation cascade (Abstract; Paragraph [0009]).
As such, Patzke discloses a test method wherein a whole blood sample is introduced into a device, a coagulation activator is added to the sample such that a cultured blood clot is formed, the cultured blood clot is allowed to incubate at 37°C, and then the amount of a secreted protein is quantifiably measured and compared to a reference value of a blood sample that does not comprise an added coagulation activator (Paragraphs [0007], [0010]-[0017], [0021], [0030], [0035]-[0036], [0053]-[0056], [0083], [0102], [0164]-[0166]).
Patzke further discloses that the coagulation activator may be a substance that activates leukocytes, for example proinflammatory cytokines (TNF-α, IL-8), which induce cell death in neutrophils (“NETosis”) and lead to the formation of neutrophil extracellular traps, which have a strongly prothrombotic effect (Paragraph [0027]).
Patzke does not disclose that the incubation time is at least 2 hours to allow the production of Lox-1 from neutrophils and shedding of soluble Lox-1 (sLox-1) outside of the cultured blood clot, as required by instant claim 1.
Tolle et al, however, disclose that CD15+/HLA-DR/CD11b+/CD14−/CD33+/Lox-1+ neutrophils form neutrophil extracellular traps (NETs), which allow for the recruitment of components of the coagulation cascade through a scaffold formation triggering thrombus formation by induction of the fibrinogenesis (Pages 7-8; Table 1; Figure 2). Tolle et al further disclose that the NETs are intended to act as an antimicrobial mechanism that capture and destroy invading pathogens through the liberation of cytotoxic molecules, but also promotes the metastasis of tumors (Pages 1-2, 6-9).
With that, Condamine et al disclose that peripheral blood samples from cancer patients have an increased sLox-1 expression after being in culture for 12 hours, wherein the sLox-1 is released from CD15+/Lox-1+ neutrophils (Pages 7-8, 11-13; Figure 6).
Therefore, it would have been prima facie obvious to have modified the method of Patzke such that the cultured blood clot is allowed to be in culture for 12 hours, wherein the secreted protein quantifiably measured is sLox-1 from CD15+/Lox-1+ neutrophils comprised within the cultured blood clot, as detailed in Condamine et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize sLox-1 as the measured protein, as it is secreted into plasma from CD15+/Lox-1+ neutrophils undergoing NETosis, and is thus an indicator of the coagulation system status of a subject. Furthermore, the ordinary artisan would have had a reasonable expectation of success given the testing protocol outlined in Patzke combined with the sLox-1 quantifiable assays performed in Condamine et al. See MPEP § 2143(I)(G).
Consequently, Patzke as modified by Tolle et al and Condamine et al render obvious a method of testing the status of a subject’s coagulation system, wherein a whole blood sample is introduced into a device, a coagulation activator is added to the sample such that a cultured blood clot – or thrombus (claim 8) – is formed, the cultured blood clot is allowed to incubate at 37°C (claim 20) for 12 hours (claim 7) such that CD15+/Lox-1+ neutrophils (claim 10) comprised within the cultured blood clot undergo NETosis and secrete sLox-1 in plasma, and then the amount of a secreted sLox-1 is quantifiably measured and compared to a reference value of a blood sample that does not comprise an added coagulation activator. This therefore renders obvious the method of instant claim 1.
Regarding claims 2 and 15: Patzke further discloses that the coagulation activator may comprise negatively charged phospholipids (claim 15) or phorbol 12-myristate 13-acetate (claim 2) (Paragraphs [0023]-[0027]). This therefore reads on the methods of the instant claims.
Regarding claims 3 and 16: Following the discussion of claim 1, Patzke further discloses that the cultured blood clot produces IL-8 and TNF-α (claim 16) (Paragraph [0027]). This therefore reads on the method of instant claim 3.
Regarding claim 4: Following the discussion of claim 1, Condamine et al further disclose that CD15+/Lox-1+ neutrophils activated with phorbol 12-myristate 13-acetate (PMA) undergo NETosis after being in culture for 18 hours, as evidenced by the significant decrease in living PMA-activated CD15+/Lox-1+ neutrophils from the 1 hour mark to the 18 hour mark as compared to untreated cells (Pages 7, 13; Figure 5E). Therefore, the ordinary artisan would have recognized that the complete NETosis of a sample having an initial population of about 60% CD15+/Lox-1+ neutrophils will result in the secretion of about 60% more sLox-1 when compared to an untreated sample. This therefore renders obvious the method of the instant claim for the same reasons as described in the discussion of instant claim 1. See MPEP § 2144.05.
Regarding claim 5: Following the discussion of claim 1, Condamine et al further disclose that the amount of sLox-1 within the plasma of peripheral blood samples from patients with colon cancer is about 200 pg/mL, or about 0.2 ng/mL (Figure 6A). This therefore renders obvious the method of the instant claim for the same reasons as described in the discussion of instant claim 1. See MPEP § 2144.05.
Regarding claim 6: Following the discussion of claim 1, Patzke further disclose that the sample of whole blood is derived from a subject as a means to determine the coagulation system status of that subject (Paragraphs [0010]). Therefore, the sLox-1 produced is an autologous sLox-1, and thereby reads on the method of the instant claim.
Regarding claim 11: Following the discussion of claim 1, Condamine et al further disclose that the CD15+/Lox-1+ neutrophils undergo polymorphonuclear myeloid-derived suppressor cell polarization (Pages 2, 4-5; Figure 5). This therefore renders obvious the method of the instant claim for the same reasons as described in the discussion of instant claim 1.
Regarding claims 14 and 22: Following the discussion of claim 1, Patzke further discloses that the tests can be utilized for the monitoring of blood samples from patients who have been treated with platelet inhibitors (claim 22) (Paragraph [0166]). As the platelet inhibitor can be considered a drug, this therefore reads on the method of instant claim 14.
Regarding claim 17: Following the discussion of claim 1, Condamine et al further disclose that CD15+/Lox-1+ neutrophils express ORL1 (Pages 2, 4). Therefore, the cultured blood clot comprising the CD15+/Lox-1+ neutrophils will also express ORL1. This renders obvious the method of the instant claim for the same reasons as described in the discussion of instant claim 1.
Regarding claim 18: Following the discussion of claim 1, Condamine et al further disclose that the PMA-activated samples comprise about 50% to about 80% of CD15+/LOX-1+ cells, compared to about 5% to about 10% of an untreated sample (Figure 5E). This therefore equates to there being about 5 times more CD15+/LOX-1+ cells in the PMA-activated sample compared to an untreated, fresh sample. This renders obvious the method of the instant claim for the same reasons as described in the discussion of instant claim 1. See MPEP § 2144.05.
Claims 1-11, 14-18, 20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Patzke (US 2023/0280359 A1) in view of Tolle et al (Int J Mol Sci, 2021) and Condamine et al (Sci Immunol, 2017), and further in view of Hao et al (Am J Blood Res, 2013).
The discussion of Patzke as modified by Tolle et al and Condamine et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporate in its entirety. Patzke as modified by Tolle et al and Condamine et al render obvious claims 1-8, 10-11, 14-18, 20, and 22. Hao et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 9: As aforementioned in the discussion of claim 1 above, Patzke as modified by Tolle et al and Condamine et al render obvious a method of testing a cultured blood clot in order to determine the status of a subject’s coagulation system.
The combination of Patzke, Tolle et al, and Condamine et al fail to teach that the neutrophils form a synapse with lymphocytes of the blood, as required by instant claim 9.
Hao et al, however, disclose that whole peripheral blood samples from cancer patients comprise CD11c bright/CD62L dim/CD11b bright/CD16 bright neutrophils (Pages 242-243). Hao et al further disclose that this subset of neutrophils is capable of forming immunological synapses with T lymphocytes (Page 239).
Therefore, it would have been prima facie obvious to modify the method of Patzke, Tolle et al, and Condamine et al such that the whole blood sample comprises CD11c bright/CD62L dim/CD11b bright/CD16 bright neutrophils that are capable of forming immunological synapses with T lymphocytes, as detailed in Hao et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to have the CD11c bright/CD62L dim/CD11b bright/CD16 bright neutrophils within the whole blood sample, as it better recapitulates cancer patient blood clots in vitro and provides a more robust analysis of their coagulation system status, and would have had a reasonable expectation of success given that the method of Patzke allows for the analysis of a whole blood sample. See MPEP § 2143(I)(G).
Consequently, Patzke as modified by Tolle et al, Condamine et al, and Hao et al render obvious a method of testing the status of a subject’s coagulation system, wherein the whole blood sample comprises CD11c bright/CD62L dim/CD11b bright/CD16 bright neutrophils that are capable of forming immunological synapses with T lymphocytes. This therefore renders obvious the method of the instant claim.
Claims 1-8, 10-11, 14-18, 20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Patzke (US 2023/0280359 A1) in view of Tolle et al (Int J Mol Sci, 2021) and Condamine et al (Sci Immunol, 2017), and further in view of Zelvyte et al (Anticancer Res, 2004) and Talens (J Thromb Haemost, 2013).
The discussion of Patzke as modified by Tolle et al and Condamine et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporate in its entirety. Patzke as modified by Tolle et al and Condamine et al render obvious claims 1-8, 10-11, 14-18, 20, and 22. Talens et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 19: As aforementioned in the discussion of claim 1 above, Patzke as modified by Tolle et al and Condamine et al render obvious a method of testing the status of a cancer patient’s coagulation system, wherein a whole blood sample from the patient is introduced into a device, a coagulation activator is added to the sample such that a cultured blood clot is formed, the cultured blood clot is allowed to incubate at 37°C, and then the amount of a secreted protein is quantifiably measured and compared to a reference value of a blood sample that does not comprise an added coagulation activator.
The combination of Patzke, Tolle et al, and Condamine et al do not teach that the secreted protein to be quantifiably analyzed is alpha-1 antitrypsin, as required by instant claim 19.
Zelvyte et al, however, disclose that alpha-1 antitrypsin (AAT) expression within the plasma of peripheral blood samples from lung cancer patients is increased when compared to healthy controls (Pages 242-243; Table 1).
With that, Talens et al disclose that the amount of AAT within plasma is directly related to the amount of fibrin within a clot (Pages 1320-1322).
Therefore, it would have been prima facie obvious to have substituted the quantifiably analyzed protein of Patzke with the alpha-1 antitrypsin of Zelvyte et al, as doing so would have been a simple substitution of one elevated cancer plasma protein for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two plasma proteins are functionally comparable as a means for indicating the coagulation system status of cancer patients, since the amount of AAT within plasma is directly related to the amount of fibrin within a clot, and thereby would have been able to substitute the plasma proteins with predictable results.
Consequently, Patzke as modified by Tolle et al, Condamine et al, Zelvyte et al, and Talens et al render obvious a method of testing the status of a cancer patient’s coagulation system, wherein the plasma protein for analysis is alpha-1 antitrypsin. As the quantifiable analysis of active alpha-1 antitrypsin allows for the determination of a subject’s coagulation system status – and thus disease state – this therefore renders obvious the method of the instant claim.
Claims 1-8, 10-11, 14-18, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Patzke (US 2023/0280359 A1) in view of Tolle et al (Int J Mol Sci, 2021) and Condamine et al (Sci Immunol, 2017), and further in view of Hoemann et al (Int J Biol Macromol, 2017).
The discussion of Patzke as modified by Tolle et al and Condamine et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporate in its entirety. Patzke as modified by Tolle et al and Condamine et al render obvious claims 1-8, 10-11, 14-18, 20, and 22. Hoemann et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 21: As aforementioned in the discussion of claim 1 above, Patzke discloses that the coagulation activator may be a substance that activates leukocytes, for example proinflammatory cytokines (TNF-α, IL-8), which induce cell death in neutrophils (“NETosis”).
The combination of Patzke, Tolle et al, and Condamine et al do not teach that the coagulation activator is chitosan, as required by instant claim 21.
Hoemann et al, however, disclose the coagulation of a whole blood clot via the administration of chitosan, wherein the addition of chitosan allows for a more chemotactic response from neutrophils, and an enhanced release of IL-8 (Pages 1920, 1923; Figures 3-4; Table 1).
Therefore, it would have been prima facie obvious to have substituted the coagulation activator of Patzke with the chitosan coagulation activator of Hoemann et al, as doing so would have been a simple substitution of one coagulation activator for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two coagulation activators are functionally comparable, as they both result in the coagulation of a whole blood sample and allow the cultured blood clot to comprise IL-8, and thereby would have been able to substitute the coagulation factors with predictable results.
Consequently, Patzke as modified by Tolle et al, Condamine et al, and Hoemann et al render obvious a method of testing the status of a subject’s coagulation system, wherein the coagulation activator is chitosan. This therefore renders obvious the method of the instant claim.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-11 and 14-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 9, 11, and 24 of copending Application No. 18/321738 in view of Tolle et al (Int J Mol Sci, 2021), Condamine et al (Sci Immunol, 2017), Patzke (US 2023/0280359 A1), Hao et al (Am J Blood Res, 2013), Zelvyte et al (Anticancer Res, 2004), Talens (J Thromb Haemost, 2013), and Hoemann et al (Int J Biol Macromol, 2017). It is of note that the instant application is a CONTINUATION-IN-PART of the copending application.
Although the claims at issue are not identical, they are not patentably distinct from each other
because the copending claims either anticipate or render obvious the instant claims. More specifically, when applicable, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are rendered obvious by the accompanying prior art.
Copending claim 1 is directed to a method, comprising:
adding a coagulation enhancing material to a blood sample ex vivo to form a cultured blood clot;
incubating the cultured blood clot at a temperature greater than 25°C and less than 45°C for at least 2 hours; and
comparing a concentration of sLox-1 (soluble Lox-1) in a cultured clot serum to a concentration of sLox-1 in: fresh blood plasma; or fresh blood serum; and
wherein the method is configured to produce autologous sLox-1.
This therefore anticipates the limitations of instant claims 1 and 6.
In addition, copending claims 2, 4-7, 9, 11 are each substantially identical to and thus anticipate instant claim 2-5, 7-8, and 16, respectively.
Copending claim 24 renders obvious the limitation of instant claim 11.
With that, although the copending application does not disclose the limitations from instant claims 9-10, 12-15, and 17-22, the subject matter is known from the prior art and can be further incorporated into the method anticipated by copending claim 1:
Tolle et al and Condamine et al teach the limitations in instant claims 10, 17-18.
Patzke teaches the limitations in instant claims 14-15, 20, and 22.
Hao et al teach the limitation in instant claim 9.
Zelvyte et al and Talens et al teach the limitation in instant claim 19.
Hoemann et al teach the limitation in instant claim 21.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633