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 ACTION
1. Applicant’s election without traverse of Group I (claims 22-37 and 40) in the reply filed on June 12, 2026 is acknowledged.
Status of the Application
2. Claims 22-37 and 40 are considered for examination. Claims 38-39 and 41-46 were withdrawn from further consideration as being drawn to nonelected group.
Priority
3. This application filed on February 06, 2024 is a 371 of PCT/IN2022/050380 filed on April 21, 2022 which claims priority benefit of IN2021018478 filed on April 21, 2021.
Informalities
4. The following informalities are noted:
(i) claims 22, 30, 37, 40 recite cancer related markers (such as Oct4A, ABL1, EVI1). Expanding reach term, at least for the first time that it appears in the claims is suggested.
Objection to the specification
5. The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (para 0095). 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. Appropriate correction is required.
Claim Rejections - 35 USC § 101
6. 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 22-37 and 40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims 22-37, 40 recite a method for detecting a medical condition in a subject and predicting the onset of a cancer, a process, statutory category. Claims 22-37 and 40 recite a judicial exception (law of nature, natural phenomenon) because claims recite a correlation of the expression of Oct4A with a medical condition or cancer, which is a law of nature or natural phenomenon that exits in nature. The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps (isolating biological sample and measuring expression level) which do not add significantly more to the claimed method. The additional steps are not themselves natural laws, but neither are they sufficient to transform the nature of the claims because they consist of well-understood, routine, conventional activity already engaged in by the scientific community. The additional steps consist of well-understood, routine, conventional activity already engaged in by the scientific community ((Tripathi et al. (WO 2019/239431); Bhartiya et al., Stem cell research & Therapy, Vol.6:96, (2015); Ratajczak et al. Stem cell Rev.Rep., Vol. 6(2), p. 307-316, (2010); Chantel et al., Molecular Cancer, Vol. 14:152, (2015); Zhao et al., Medicine, Vol. 99(42), e22804, (2020))). The additional steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. The Court has made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words "apply it." Essentially, appending conventional steps specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible. This judicial exception is not integrated into a practical application because the judicial exception is not markedly different from the natural phenomenon because the claims recite the abstract idea of determining by a computer processing. It is noted that a judicial exception itself, such as an abstract idea, cannot be considered to meet the criteria of "significantly more" than a judicial exception. The Courts decision rested upon an examination of the particular claims in light of the Court's precedents, specifically Bilski, Flook and Diehr. The Court repeated the long standing exceptions (laws of nature, natural phenomena, and abstract ideas) to categories of patent eligibility defined in 35 U.S.C. § 101. In conducting the analysis, the Court addressed the "machine-or-transformation" test explained in Bilski with a reminder that the test is an "important and useful clue" to patentability but that it does not trump the "law of nature" exclusion. A claim that recites a law of nature or natural correlation, with additional steps that involve well-understood, routine, conventional activity previously engaged in by researchers in the field is not patent-eligible, regardless of whether the steps result in a transformation. On the other hand, reaching back to Neilson, the Court pointed to an eligible process that included not only a law of nature (hot air promotes ignition) but also several unconventional steps involving a blast furnace) that confined the claims to a particular, useful application of the principle. For all the above, the claims are rejected under 35 USC 101.
Double Patenting
7. 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.
A. Claims 22-36 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US patent 11,926,875 (here after the ‘875). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims 22-36, 40 are entirely within the scope of the claims 1-18 of the patent ‘875. Specifically, the method steps comprising obtaining a blood sample from a subject, adding salt solution, layering the sample over a neutral buffer, subjecting the sample to a density gradient, lysing the RBCs, centrifuging lysed solution, subjecting cell pellet to cell lysis ad extracting RNA molecules, assaying the RNA molecules to determine an expression level of Oct 4A, comparing with a reference expression level of Oct4A and predicting the onset of a medical condition or cancer in the subject are within the scope of the claims 1-18 of the patent ‘875 and are coextensive in scope.
B. Claims 22-36 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US patent 12,618,114 (here after the ‘114). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims 22-36, 40 are entirely within the scope of the claims 1-16 of the patent ‘114. Specifically, the method steps comprising obtaining a blood sample from a subject, adding salt solution, layering the sample over a neutral buffer, subjecting the sample to a density gradient, lysing the RBCs, centrifuging lysed solution, subjecting cell pellet to cell lysis ad extracting RNA molecules, assaying the RNA molecules to determine an expression level of Oct 4A, comparing with a reference expression level of Oct4A and predicting the onset of a medical condition or cancer in the subject are within the scope of the claims 1-16 of the patent ‘114 and are coextensive in scope.
C. Claims 22-36 and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-6, 14-19, 23, 31, 37, 54-59 of copending Application No. 17/998,252. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims 22-36, 40 are entirely within the scope of the claims 3-6, 14-19, 23, 31, 37, 54-59 in the co-pending application Specifically, the method steps comprising obtaining a blood sample from a subject, adding salt solution, layering the sample over a neutral buffer, subjecting the sample to a density gradient, lysing the RBCs, centrifuging lysed solution, subjecting cell pellet to cell lysis ad extracting RNA molecules, assaying the RNA molecules to determine an expression level of Oct 4A, comparing with a reference expression level of Oct4A and predicting the onset of a medical condition or cancer in the subject are within the scope of the claims in the co-pending application and are coextensive in scope.
Claim Rejections - 35 USC § 102
8. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 22-28, 30-34, 36-37 and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tripathi et al. (WO 2019/239431).
Tripathi et al. teach n in-vitro method of claim 22, for detecting a medical condition in a subject, and an in-vitro method for predicting onset of cancer or detecting a presence of tumor or cancer in a subject of claim 30, comprising: (a) obtaining a blood sample from the subject (page 66, para 00206, 0089, 00118-00120); (b) adding a salt solution to the blood sample (para 00206, 0089, 00118-00120); (c) layering the blood sample over a neutral buffer (para 000206, 0089, 00118-00120); (d) subjecting the blood sample to a density gradient centrifugation at a speed of between 200 g and 900 g to obtain a first pellet comprising red blood cells (RBCs) (para 00206-00212, 0089, 00118-00120); (e) lysing the RBCs to obtain an RBC-lysed solution (para 00206-00212, 0089, 00120); (f) centrifuging the RBC-lysed solution at a speed of between 400 g and 4000 g to obtain a second pellet (para 00206-00212, 0089, 00108, 00118-00120); (g) subjecting the second pellet to cell lysis and extracting ribonucleic acid (RNA) molecules from the second pellet (para 00206, 00118-00120); (h) assaying the RNA molecules to determine an expression level of Oct 4A (para 00206-00212, 00118-00120); and (i) comparing the expression level of Oct 4A with a reference expression level of Oct 4A, wherein an increase of 1.1 to 3 folds in the expression level of Oct 4A as compared to the reference expression level of Oct 4A indicates a presence of the medical condition in the subject (para 00206-00208, 00106-00107, 00113-00124).
With reference to claim 23, 31, Tripathi et al. teach that the blood sample is a peripheral blood sample (para 00206, 00118-00120).
With reference to claim 24, 32, Tripathi et al. teach that extracting the RNA molecules comprises a technique selected from the group consisting of: guanidinium thiocyanate-phenol- chloroform nucleic acid extraction, cesium chloride gradient centrifugation, cetyltrimethylammonium bromide nucleic acid extraction, alkaline extraction, resin-based extraction, and solid phase nucleic acid extraction (para 0085, 00108, 00118-00120).
With reference to claim 25, 33, Tripathi et al. teach that assaying the RNA molecules comprises a technique selected from the group consisting of: quantitative polymerase chain reaction (PCR), flow cytometry, and next-generation sequencing (NGS) (para 0086).
With reference to claim 26-27 Tripathi et al. teach that wherein the medical condition is selected from the group consisting of multiple sclerosis, kidney disorders, skin disease, liver disease, lung disease, cardiovascular diseases, osteoarthritis, viral disease, cancer, and diabetes, wherein the condition is cancer (para 00106-00107).
With reference to claim 28, 34, Tripathi et al. teach that the neutral buffer comprises Ficoll Hypaque solution (para 0212, 00108, 00121).
With reference to claim 36-37, Tripathi et al. teach performing a sequence- based assay on the RNA molecules to detect a mutation in at least one cancer-related marker which includes ABL1, wherein a detected presence of the mutation in the at least one cancer-related marker indicates presence of a specific type of cancer (para 0013-0014, 0075, 00113-00124, 0179).
With reference to claim 40, Tripathi et al. teach that an increase of 5 to 10 folds in the expression level of Oct 4A as compared to the reference expression level of Oct 4A indicates stage-I of cancer, wherein an increase of 10 to 15 folds in the expression level of Oct 4A as compared to the reference expression level of Oct 4A indicates stage-II of cancer, wherein an increase of 15 to 20 folds in the expression level of Oct 4A as compared to the reference expression level of Oct 4A indicates stage-III of cancer, and wherein an increase of at least 20 folds in the expression level of Oct 4A as compared to the reference expression level of Oct 4A indicates stage-IV of cancer (para 0081-0093, 00113-00124). For all the above, the claims are anticipated.
Claim Rejections - 35 USC § 103
9. 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.
Claims 22-37 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Tripathi et al. (WO 2019/239431) in view of Guia et al. (WO 2018/191534).
Tripathi et al. teach a method for detecting and predicting onset of cancer as discussed above in section 8. However, Tripathi et al. specifically did not teach lysing the RBCs comprises treating the first pellet with ammonium chloride.
Guia et al. teach a method for separating and enriching cells from a blood sample, the method comprises lysing whole blood sample with ammonium chloride to lyse the red blood cells or erythrocytes and separating leukocytes from the blood sample (para 00156, 00573, 00487, 00635).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the invention to combine the method of Tripathi et al. with RBC lysis with ammonium chloride as taught by Guia et al. to develop an improved method for isolating leukocytes from the blood sample. The ordinary person skilled in the art would have motivated to combine the method as taught by Tripathi et al. with ammonium chloride as taught by Guia et al. and have a reasonable expectation of success that the combination would result in improved method for processing a blood sample because Guia et al. explicitly taught use of ammonium chloride to lyse RBC which cause lysis of RBC by osmotic pressure without inhibiting viability of leukocytes (para 00156, 00487) and such a modification of the method is considered obvious over the prior art.
Conclusion
No claims are allowable.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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