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 .
Election/Restriction
Applicant's election without traverse of Invention group II, claims 1-10 drawn to a preparation method of an autophagosome for promoting healing of a diabetic wound, in the reply filed on 06/22/2026 is acknowledged.
Claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/22/2026.
Claim Status
Claims 1-15 are pending
Claims 11-15 are withdrawn
Claims 1-10 are under examination
Claim objections
Please revise claim 5 to recite ‘with a LC3-labeled’ instead of the phrase ‘with an LC3- labeled’.
Claim Rejections - 35 USC § 112 (a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for capturing autophagosome by incubating the precipitate produced by the method of claim 1 with LC3 antibody labelled magnetic beads, does not reasonably provide enablement for capturing the autophagosome by incubating the said precipitate in LC3 labelled magnetic beads. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make use the invention to capture an autophagosome by using the LC3-labeled magnetic beads, commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, the enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention:
The invention is drawn to a method of preparing an autophagosome in vascular endothelial cells.
(2) Breadth of the claim(s):
Claim 5 is drawn to a method of preparing an autophagosome and capturing the said autophagosome.
(3) The state of the prior art:
Xi Chen et al., 2014 identifies LC3 as a biomarker associated with mature autophagosomes. Magnetic beads or Dynabeads labeled with anti-bodies targeting the LC3 markers present on autophagosomes is a known method, that’s being used to immunoprecipitate/isolate autophagosome from other cellular components (Xi Chen et al., 2014, materials and methods, page 181 and Schwertz et al., 2021, co-immunoprecipitation studies, page 1547).
(4) The predictability or unpredictability of the art:
Prior art does not predict the capability of the LC3-labeled magnetic beads to capture autophagosome. Prior art only teaches the conjugation of magnetic beads with antibodies that target LC3 (ex: anti-GFP antibody to target GFP-LC3), to isolate autophagosomes (Xi Chen et al., 2014, materials and methods, page 181 and Schwertz et al., 2021, co-immunoprecipitation studies, page 1547).
(5) The relative skill of those in the art:
The relative skill of those in the art is high, requiring a graduate degree.
(6) The amount of guidance presented:
Claim 5 and specification when taken together do not provide sufficient guidance to capture autophagosome using LC3-labeled magnetic beads, because LC3 is a protein found on autophagosomes( Xi Chen et al., 2014). Claim 5 and specification (0026) recite that the precipitate obtained from claim 1 is incubated with a LC3 labeled magnetic bead to capture the autophagosome, and do not provide further clarification on how this is achieved. Therefore, it is not clear how a protein present on the surface of the autophagosome i.e. LC3 is used in conjunction with magnetic beads to capture the autophagosome.
(7) The presence of working examples:
Specification example 1 recites magnetic bead co-incubated with LC3 antibody being used to capture autophagosomes. Therefore it’s not clear how LC-3 labeled magnetic beads and no the LC3-antibody labeled magnetic beads are used to capture autophagosomes as recited in claim 5.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the claimed invention within the scope of capturing autophagosomes. For example, one of ordinary skill in the art would have to perform undue amount of experimentation to figure out how to capture the autophagosomes with LC3-labeld magnetic beads.
Therefore , claim 5 and all the dependent claims including claim 10 are rejected under 35 U.S.C 112, first paragraph, for scope of enablement.
Claim Rejections - 35 USC § 112 (b)
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.
Regarding claim2, the claim contains the trademark names Gibco high-glucose Dulbecco’s Modified Eagle Medium (DMEM). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe cell culture media and, accordingly, the identification/description is indefinite.
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 6-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more.
The claims 6-10 recite ‘an autophagosome’. According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories (i.e. process, machine, manufacture, or composition of matter). Claims 6-10 are drawn to a composition of matter comprising ‘an autophagosome’. Thus claim 6-10 meet the requirements for step 1 of the analysis.
Second, the claims are assessed to determine if they are directed to a judicial exception under step 2A. Under 2019PEG, “directed to” is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application”, requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application).
Regarding the first prong (1), claims 6-10 are directed to ‘an autophagosome’. Wollert et al., 2019 teaches that autophagosomes are formed by the cellular process ‘autophagy’ which is essential for cellular survival and maintenance of homeostasis (page R671). Thus, the first prong of the inquiry demonstrates that claims 6-10 recite a judicial exception, a product of nature.
Regarding the second prong (2), Claims 6-10 recite additional elements that the autophagosome recited in each claim is “prepared” by the preparation method according to claims 1-5 respectively. The term “prepared” further describes cultivating and centrifuging vascular endothelial cells in the respective claims (limitations after wherein clause of claim 5 is not given patentable weight, see USC 103 rejection). The recited methods solely describe the means by which the claimed autophagosomes are made. The intended use ‘for promoting healing of a diabetic wound’ recited in the independent claim is intentional and do not recite patentable limitations that may integrate the recited methods of preparation or the autophagosomes into a practical application. Thus, since the additional element solely describe a means by which the autophagosome is made, the claims 6-10 do not recite any additional elements or a combination thereof that integrate the judicial exception identified in prong 1 into a practical application. Further since the claims 6-10 are not meaningfully limited to any particular practical application, the generic nature of the claim appears to monopolize the claimed method. Thus, claims 6-10 meet the requirement of step 2A as being directed to a judicial exception.
Third, if a judicial exception is present in the claim, it is further assessed to determine if the claim recites any additional elements or steps that are sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. As discussed above, the claims recite the structural element of “prepared”. It is noted that “prepared” does impart a structural distinction to the claimed autophagosomes in claims 6-10 because in nature autophagosomes are not prepared but rather are found within cells. However, the claimed prepared autophagosomes are structurally indistinguishable from the autophagosomes found in cells in vivo, because they are naïve or unaltered having the same structural and functional features of autophagosomes occur in vivo.
Under the holding of Myriad, an isolated but otherwise unchanged nucleic acid was not patent eligible subject matter because it was not different enough from what exists in nature to avoid improperly tying up the future use and study of naturally occurring nucleic acid. The ‘prepared autophagosomes’ in claims 6-10 are analogous to the ‘isolated nucleic’ acid in Myriad. The claimed autophagosomes can be interpreted as being a captured autophagosomes that are otherwise unchanged. Thus, similar to the isolated nucleic acid, the prepared/captured autophagosome is not patent eligible subject matter because it is not different enough from the autophagosomes that exists in nature to avoid improperly tying up the future use and study of the naturally occurring autophagosomes.
Thus, as a whole, claims 6-10 do not impart any structural or functional distinctions to the claimed product ‘autophagosome’ that would distinguish it from a autophagosome found in nature. As such, claims 6-10 do not meet the requirements of step 2B of the 2019PEG because the prepared/captured autophagosomes and the method by which the claimed autophagosomes were prepared do not impart a significant distinction to the claimed autophagosomes to distinguish them from autophagosomes found in cells in vivo.
In conclusion, claims 6-10 meet all the requirements of the 2019PEG and therefore deemed patent ineligible.
Claim Rejections - 35 USC § 102
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 6-10 are rejected under 35 U.S.C. 102(1) as being anticipated by Bains et al., STAR protocols 2.3 (2021).
Regarding claims 6-10, these claims are drawn to the product ‘a prepared autophagosome’, and the process by which the product is made is does not further structurally or functionally limit the product. Therefore, the process by which the autophagosomes are made do not carry patentable weight in these claims.
Regarding claims 6-10, Bains teach a prepared autophagosome (abstract figure and page 1).
Therefore, the reference anticipate the claimed invention.
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 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 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 1 ,4, 5, 6, 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Bains et al., STAR protocols 2.3 (2021) and Chen et al., Cellular Physiology and Biochemistry 33.4 (2014): 1058-1074.
Regarding claim 1, Bains teaches a high -yielding (summary, page 1) preparation method of an autophagosome from liver cells and subjecting the cells prepared for isolation of autophagosome to a first centrifugation to obtain the first supernatant, and subjecting the first supernatant to a second centrifugation to obtain a precipitate comprising the autophagosome. Bains also teaches that the first centrifugation was done at 2000g for 10 minutes in two consecutive steps for 5 minutes each where the supernatant was collected and subjected to a second centrifugation which was conducted at 17000g for 12 minutes (sequential centrifugation, page 5).
Bains does not teach the exact centrifugal force and duration of time on the second centrifugation step and cultivating a vascular endothelial cells in a serum-free medium.
However one of ordinary skill in the art would have recognized that the centrifugal force and the duration of the second centrifugation step could be optimized to obtain the desired results. Please see MPEP 2144.05 II routine optimization.
.
Also, before the effective filling date of the claimed invention, cultivating a vascular endothelial cell in a serum-free medium was known in the art.
Chen teaches cultivating human umbilical vein endothelia cells (HUVECS) in serum-free media (cell culture, page 1060), in a study that teaches high-glucose induced autophagic response ,because these culture conditions induced autophagy and the formation of autophagosomes(discussion 1070)
Also, the intended use recited in the claim, for promoting healing of a diabetic wound is not given patentable weight, because it solely an intention and does not further limit the claimed method.
Therefore, before the effective filling date of the claimed invention, Bain teaches a preparation method of an autophagosome from liver cells and Chen teaches cultivating HUVECs in serum-free media. Accordingly, it would have been obvious to a person of ordinary skill in the art to replace the liver cells in Bain with HUVECs cultivated in serum-free media taught by Chen to prepare an autophagosome, because autophagosome formation in HUVECs can be induced under the culture conditions taught by Chen. There would be a reasonable expectation of success to combine the teachings of Bains and Chen, because Bain teaches a method to prepare autophagosomes in a high-yield and Chen teaches a method to culture vascular endothelial cells that induce autophagosome formation.
Regarding claim 4, Bain teaches conducting the first and the second centrifugations at 40C (sequential centrifugation, page 5).
Regarding claim 5, the combined teachings of Bain and Chen would have made the preparation method of an autophagosome obvious to a person of ordinary skill in the art, prior to the effective filling date of the invention.
The wherein clause in claim 5, does not constitute an active step in the requisite method to prepare an autophagosome, rather recites a step to capture the autophagosome. Therefore, the ‘wherein’ clause in the claim is interpreted as a positively recited intent to capture the autophagosome which does not change the end result of the method of preparing autophagosome. Therefore the limitations recited after the wherein clause is not given patentable weight.
Please see MPEP 2111.04 "Adapted to," "Adapted for," "Wherein," "Whereby," and Contingent Clauses [R-10.2019]
I. "ADAPTED TO," "ADAPTED FOR," "WHEREIN," AND "WHEREBY"
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. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
• (A) "adapted to" or "adapted for" clauses;
• (B) "wherein" clauses; and
• (C) "whereby" clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Hence, the claimed invention as a whole was prima facie obvious.
Claims 2, 3 ,7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Bains et al., STAR protocols 2.3 (2021) and Chen et al., as applied to claim 1, 4 and 5 above, and further in view of Thormodsson et al., Methods and protocols (2018).
Teachings of Bains and Chen are as relied on above.
Regarding claim 2, Chen also teaches culturing HUVECs high-glucose culture media (fig 1., page 1062) .
Chen does not teach cultivating vascular endothelial cells in a medium comprising 0.1% penicillin-streptomycin.
However, before the effective filling date of the claimed invention, cultivating a vascular endothelial cell in a medium comprising 0.1% penicillin-streptomycin was known in the art.
Thormodsson teaches culturing HUVECs in culture medium containing 400 µl of penicillin-streptomycin solution in a total of 40ml culture medium ( 2.2 Reagents, 11. Culture medium for HUVECS, page 357)which results in 0.1 % (vol/vol) penicillin-streptomycin in the culture medium, in their published protocol.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to combine the above mentioned teachings of Bains, Chen and Thormodsson to develop a method to prepare autophagosomes from cultivated vascular endothelial cells. One of ordinary skill in the art would have been motivated to combine the teachings of Bains and Chen to prepare autophagosomes from vascular endothelial cells cultured in serum-free, high-glucose culture media containing 0.1% penicillin-streptomycin. There would be a reasonable expectation of success to combine the teachings of Bains, Chen and Thormodsson, because Thormodsson teaches the use of 0.1% penicillin-streptomycin in culture media as routine HUVEC culture procedure.
Regarding claim 3, Chen teaches culturing HUVECS in serum-free media for 48 hrs. (fig 1., page 1062) .
Hence, the claimed invention as a whole was prima facie obvious.
Conclusion
No claim is allowed.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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