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 .
Status of the Application
Claims 1-11, 13-22 and 27-29 are pending, of which claims 13-21 and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-11, 22, 27 and 29 are under current examination.
Amendment necessitated new claim rejection as set forth below.
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 1-11, 22, 27 and 29 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 pre-AIA the applicant regards as the invention.
Claims 1-11, 22, 27 and 29 are indefinite as:
claim 1 recites “wherein the hydrogel dissolves ---- below 45C by at least one of –(i)----(iii) lowering the temperature from about 20-40C to about 2C-10C---(iv)---”. This is because the claim first provides a limitation of below 45C and by doing one of (i)-(iv) and then (iii) of those statements includes lowering of temperature. Thus, making it unclear if any of the statements (i)-(iv) needs to be satisfied. The claim is further indefinite as claim recites both broad and narrow limitation of temperature for dissolving the hydrogel. Thus, making scope of claim unclear. For compact prosecution the claim has been interpreted as “wherein the hydrogel dissolves at a temperature below 45C.
Claim 1 is further indefinite as the claim recites “manipulating---and wherein hydrogel dissolves” that the claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In this case, the phrase makes limitation optional.
Claim 4 is indefinite as the claim recites “further comprising (c) lysing the organelle or---acid”, as, it is unclear where this step is executed in the process. Is this step is done before manipulating nucleic acid or after manipulation. Because of indefiniteness brought by claim 4, claim 4 limitation of step (c) has not been searched for the prior art and is not examined.
Claim 10 is indefinite as the claim recites “manipulated nucleic acid is an isolated ---uHMW ---at least 1000kb”. This is because claim 1 recites “a hydrogel comprising a long manipulated nucleic acid”, thus long manipulated nucleic acid cannot be without hydrogel. One independent claim and Claims dependent on it can have one objective, which in this case is obtaining a hydrogel comprising a long manipulated nucleic acid and not an isolated nucleic acid as recited in claim 10. It is unclear what applicant regards as the invention. Thus, making objective of the claims unclear. The claims create confusion as to when direct infringement occurs. Katz, 639 F.3d at 1318, 97 USPQ2d at 1749 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited "an input means" and required a user to use the input means was found to be indefinite because it was unclear "whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means."); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph). In this case, the claims create confusion as to when direct infringement occurs "whether infringement … occurs when one invents a method that allows to obtain a hydrogel having a manipulated nucleic acid, or whether infringement occurs when one invents a method that allows to sequence a nucleic acid [by degrading a hydrogel]. Because of indefiniteness and ambiguity brought by this claim, this claim limitation has not been searched for the prior art and is not examined.
Claim 22 recites “further comprising (d) modifying the nucleic acid---library”. This is because step c of claim 1 recites manipulating nucleic acid and it is unclear if modifying is not part of manipulating and in what ways it is different from step c of claim 1. Further, manipulating encompass the word modifying.
Since the dependent claims doesn’t cure the above deficiencies, these claims are also indefinite.
Appropriate correction required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 10 is rejected under 35 U.S.C. 112(d), as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 10 is in an improper dependent form because claim 10 dependent on claim 1 recites “wherein the long manipulated nucleic acid is an isolated ---uHMW”. However, claim 1 is limited to obtain a hydrogel comprising a long manipulated nucleic acid and not an isolated nucleic acid.
Applicant may cancel or amend the claim.
Claim Rejections - 35 USC § 102
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 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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 8-11, 22, 27 and 29 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Khurana (WO2019028047 A1; as provided by the applicant on IDS dated 06/10/2022).
Khurana discloses a method of obtaining a hydrogel comprising long manipulated nucleic acid, with example of nucleic acid of sizes 100kb, 150kb, 500kb or length longer than 100kb, >300bps (reads on size and MW of the nucleic acid), wherein the nucleic acid is stabilized in a hydrogel microsphere, comprising the steps of combining a nucleic acid, provided in a carrier, such as cell, with an aqueous polymer solution, such as alginate; gelling the polymer solution to form a hydrogel comprising the nucleic acid and manipulating/ modifying the nucleic acid in the hydrogel, such as amplification, making sequencing library, loading on a sequencer flow cell, dissolving the hydrogel/ degrading the hydrogel using reducing agents such as strong base comprising sodium ion at room temp (i.e., 20-25C, which is lower than 40C) or in absence of any agent by elevating the temperature such as 50C etc., addition of a sequencing buffer, and sequencing the library (entire application, especially, abstract, Pages 17-19, 24, 25, 29, 30, 33, 39, 40, 44, 45, 47, 48, 50-63 examples, especially examples 1-11, and claims).
Further, with regards to limitation “wherein the hydrogel dissolves at a temperature below 45C”-the limitation is an optional limitation. Please see rejection under 112b and claim interpretation. Since the cited prior art teaches same hydrogel made by even same steps, the physical properties of the hydrogel, such as “wherein the hydrogel dissolves at a temperature below 45C or doing even any step such as i”, is expected to be present in the hydrogel of the cited prior art, whether or not recognized by the cited prior art. This is because a composition (in this case hydrogel) is inseparable from its physical and chemical properties.
With regard to the limitation of the instant claims, “nucleic acid is manipulated to obtain a sequencing library or a long-read sequencing library”, since the cited prior art teaches same method of manipulating nucleic acid, the manipulated nucleic acid so obtained from the cited prior art is also capable of being useful in obtaining a sequencing library or a long-read sequencing library. Further, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000).
Since the cited prior art reads on all the limitations of the instant claims 1-5, 8-11, 22, 27 and 29, these claims are anticipated.
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 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 of this title, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-11, 22, 27 and 29 and elected species are rejected under 35 U.S.C. 103 as being unpatentable over Khurana (WO2019028047 A1; as provided by the applicant on IDS dated 06/10/2022).
Determining the scope and contents of the prior art
Khurana discloses a method of obtaining a hydrogel comprising long manipulated nucleic acid, with example of nucleic acid of sizes 100kb, 150kb, 500kb or length longer than 100kb, >300bps (reads on size and MW of the nucleic acid), wherein the nucleic acid is stabilized in a hydrogel microsphere, comprising the steps of combining a nucleic acid, provided in a carrier, such as cell, with an aqueous polymer solution, such as alginate; gelling the polymer solution to form a hydrogel comprising the nucleic acid and manipulating/ modifying the nucleic acid in the hydrogel, such as amplification, making sequencing library, loading on a sequencer flow cell, dissolving the hydrogel/ degrading the hydrogel using reducing agents such as strong base comprising sodium ion at room temp (i.e., 20-25C, which is lower than 40C) or in absence of any agent by elevating the temperature such as 50C etc., addition of a sequencing buffer, and sequencing the library (entire application, especially, abstract, Pages 17-19, 24, 25, 29, 30, 33, 39, 40, 44, 45, 47, 48, 50-63 examples, especially examples 1-11, and claims).
Further, with regards to limitation “wherein the hydrogel dissolves at a temperature below 45C”-the limitation is an optional limitation. Please see rejection under 112b and claim interpretation. Since the cited prior art teaches same hydrogel made by even same steps, the physical properties of the hydrogel, such as “wherein the hydrogel dissolves at a temperature below 45C or doing even any step such as i”, is expected to be present in the hydrogel of the cited prior art, whether or not recognized by the cited prior art. This is because a composition (in this case hydrogel) is inseparable from its physical and chemical properties.
With regard to the limitation of the instant claims, “nucleic acid is manipulated to obtain a sequencing library or a long-read sequencing library”, since the cited prior art teaches same method of manipulating nucleic acid, the manipulated nucleic acid so obtained from the cited prior art is also capable of being useful in obtaining a sequencing library or a long-read sequencing library. Further, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000).
Ascertaining the differences between the prior art and the claims at issue
Khurana teaches applicants process and provides that polymer for making hydrogel may be alginate. However, cited prior art fails to teach a working example with alginate as polymer for making hydrogel.
Resolving the level of ordinary skill in the pertinent art
With regards to the above difference, Khurana discloses a method of obtaining a hydrogel comprising long manipulated nucleic acid, with example of nucleic acid of sizes 100kb, 150kb, 500kb or length longer than 100kb, >300bps (reads on size and MW of the nucleic acid), wherein the nucleic acid is stabilized in a hydrogel microsphere, comprising the steps of combining a nucleic acid, provided in a carrier, such as cell, with an aqueous polymer solution, such as alginate; gelling the polymer solution to form a hydrogel comprising the nucleic acid and manipulating/ modifying the nucleic acid in the hydrogel, such as amplification, making sequencing library. Thus, with the guidance provided by the cited prior art, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that alginate may be used as a polymer to make hydrogel as suggested by the cited prior art.
Based on the above established facts, it appears that the teachings of above cited prior art read applicants’ process.
Therefore, all the claimed elements were known in the prior art and one skilled person in the art could have modified the elements as claimed by known methods with no change in their respective functions, and the modification would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Considering objective evidence present in the application indicating obviousness or nonobviousness
To establish a prima facie case of obviousness, three basic criteria must be met: (1) the prior art reference must teach or suggest all the claim limitations; (2) there must be some suggestion or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings; and (3) there must be a reasonable expectation of success; and (MPEP § 2143).
In this case, Khurana discloses a method of obtaining a hydrogel comprising long manipulated nucleic acid, with example of nucleic acid of sizes 100kb, 150kb, 500kb or length longer than 100kb, >300bps (reads on size and MW of the nucleic acid), wherein the nucleic acid is stabilized in a hydrogel microsphere,, comprising the steps of combining a nucleic acid, provided in a carrier, such as cell, with an aqueous polymer solution, such as alginate; gelling the polymer solution to form a hydrogel comprising the nucleic acid and manipulating/ modifying the nucleic acid in the hydrogel, such as amplification, making sequencing library.
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” (Id. At 1395). See MPEP 2143 - Examples of Basic Requirements of a Prima Facie Case of Obviousness [R-9].
In this case at least prong (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success would apply.
The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at ___, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. Further, there is a reasonable expectation of success that alginate may be used for making hydrogel and can be made by teachings of the above cited prior art.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited references and to make the instantly claimed process with a reasonable expectation of success.
Response to Arguments
Applicant’s remarks and amendment, filed on 11/10/2025, have been fully considered but not found persuasive.
Applicant argue that Khurana mentions nucleic acid of size 3 Mbp, these nucleic acid molecules are genetic material that has not been manipulated. Applicant also argue that Khurana only teaches fragmenting or digesting nucleic acid
This is not found persuasive and the instant claims stand rejected. This is because Khurana’s mentioning of nucleic acid of size 3 Mbp, does not precludes the teaching of Khurana a method of obtaining a hydrogel comprising long manipulated nucleic acid, with example of nucleic acid of sizes 100kb, 150kb, 500kb or length longer than 100kb, >300bps (reads on size and MW of the nucleic acid), wherein the nucleic acid is stabilized in a hydrogel microsphere,, comprising the steps of combining a nucleic acid, provided in a carrier, such as cell, with an aqueous polymer solution, such as alginate; gelling the polymer solution to form a hydrogel comprising the nucleic acid and manipulating/ modifying the nucleic acid in the hydrogel, such as amplification, making sequencing library.
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With regard to Applicant argument that Khurana only teaches fragmenting or digesting nucleic acid is again not found persuasive. This is because (1) Khurana teaches manipulation of nucleic acid in hydrogel including fragmentation, digestion, amplification, making library etc.; (2) steps of fragmentation, digestion etc., are all manipulation steps.
Rest of applicant’s argument is moot in view of new rejection as set forth above.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Conclusion
No Claim is allowed.
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/PANCHAM BAKSHI/Primary Examiner, Art Unit 1623