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/Restrictions
Applicant’s election without traverse of Group II, claims 10-15, in the reply filed 4/20/2026 is acknowledged.
Claims 1-9 and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/20/2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) filed on 8/25/2023 and 4/20/2026 are in compliance with 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to because the numbering in Fig. 1 is illegible or difficult to read. Ensure that the text is larger than 0.08 in (37 CFR 1.52). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 14 objected to because of the following informalities:
In claim 14, “bufferand” should read “buffer and”.
Appropriate correction is required.
Claim Interpretation
In claim 10, the cell lysis buffer separation apparatus according to claim 1 is interpreted to be the cell lysis buffer recited in withdrawn claim 1. The term “multiplex” is interpreted under the broadest reasonable interpretation (BRI) as meaning “multiple-part” or “multi-part”
Claim Interpretation - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“filtration device”: (claim 1)
Interpretation: a filter comprising a filter membrane, “the filtration device is a multiplex filtration device”, (pg. 2, para. 4); “the multiplex filtration device comprises a crude liquid filtration device”, (pg. 2, para. 5); “the filtration material of the multiplex filtration…is a filter membrane”, (pg. 3, para. 11-12)
“enrichment module”: (claim 10)
Interpretation: a module comprising a cell lysis buffer separation apparatus: “the enrichment module comprises a cell lysis buffer separation apparatus” (pg. 6, para. 1 in the specification),
“fermentation module”: (claim 11)
“culture device”: (claim 11)
“fermentation device”: (claim 11)
“lysis device”: (claim 11)
“purification module” : (claim 12)
“chromatography device set”: (claim 13)
“chromatography device”: (claim 13)
“protease liquid supply device”: (claim 13)
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 11-15 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 claims 11, 13, and 14, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 13 recites the limitation "the chromatography device is located in an isolator" in line 3. There is insufficient antecedent basis for “the chromatography device” in the claim. It is suggested to amend the claim language to read “the chromatography device set is located in an isolator” or “a chromatography device is located in an isolator”.
The term “low” in claim 14 is a relative term which renders the claim indefinite. The term “low” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Although the specification recites in page 7, “Further preferably, the low toxicity is relative to the high toxicity after the activation. In a specific embodiment, the activity of the toxin polypeptide after the activation is at least 5000 folds higher than that of the single-chain polypeptide, and still further, the activity of the toxin polypeptide after the activation is 6000, 7000, 8000, 9000, 10000, 12000, 15000 or more folds higher than that of the single-chain polypeptide”, this preferred embodiment is not limiting. The term is not defined in the specification as to provide an objective assessment of what is considered “low”, and thus the threshold of what is considered “low-toxic” would not be clear to a skilled artisan. For this reason, the limitation “low-toxic” in claim 14 is considered indefinite.
Claim 15 is similarly rejected as it depends upon rejected claim 14.
The following claim limitations invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
“fermentation module”: (claim 11)
“culture device”: (claim 11)
“fermentation device”: (claim 11)
“lysis device”: (claim 11)
“purification module” : (claim 12)
“chromatography device set”: (claim 13)
“chromatography device”: (claim 13)
“protease liquid supply device”: (claim 13)
However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. The specification is devoid of adequate structure to perform the claimed functions.
Regarding the limitation “fermentation module”, the specification merely recites structure also subject to 112(f) interpretation. E.g., in pg. 6, para. 3, “the fermentation module comprises a host cell culture device and a lysis device, and the lysis device”. The specification does not disclosure of any particular structure, either explicitly or inherently, to perform the fermenting.
Regarding the limitation “culture device”, the specification does not disclose any particular structure, either explicitly or inherently, to culture the host cell.
Regarding the limitation “fermentation device”, the specification does not disclose any particular structure, either explicitly or inherently, to perform the fermenting.
Regarding the limitation “lysis device”, the specification does not disclose any particular structure, either explicitly or inherently, to lyse the host cell.
Regarding the limitation “purification module”, the specification merely recites structure also subject to 112(f) interpretation. E.g., in pg. 6, para. 9, “the purification module comprises at least 1 chromatography device set”. The specification does not disclose any particular structure, either explicitly or inherently, to perform the purifying.
Regarding the limitation “chromatography device set”, the specification does not disclose any particular set of structures, either explicitly or inherently, to perform chromatography.
Regarding the limitation “chromatography device”, the specification merely recites structure also subject to 112(f) interpretation. E.g., in pg. 6, para. 11, “the chromatography devices are the same or different; more preferably, the chromatography device is an affinity chromatography device, gel filtration chromatography device, and/or ion chromatography device”. The specification does not disclose any particular structure, either explicitly or inherently, to perform affinity chromatography, gel filtration chromatography, and/or ion chromatography.
Regarding the limitation “protease liquid supply device”, the specification does not disclose any particular structure, either explicitly or inherently, to supply protease liquid.
As would be recognized by those of ordinary skill in the art, there are many different structures capable of performing each of the claimed functions. The specification does not provide sufficient details such that one of ordinary skill in the art would understand which structures perform the claimed functions. Therefore, claims 11-13 are indefinite and are rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
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 11-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. As described above, the disclosure does not provide adequate structure to perform the claimed functions of fermenting, culturing the host cell, fermenting the host cell, lysing the host cell, purifying, or affinity, gel filtration, and/or ion chromatography. The specification does not demonstrate that applicant has made an invention that achieves the claimed functions because the invention is not described with sufficient detail that one of ordinary skill in the art can reasonably conclude that the inventor had possession of the claimed invention.
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.
Claims 10-15 are rejected under 35 U.S.C. 103 as being unpatentable over Ton et al. (US 2011/0008843 A1) (see PTO-892; hereinafter Ton).
Regarding claim 10, Ton discloses a system for preparing a polypeptide (abstract, “processes and systems for obtaining…botulinum neurotoxin”), wherein the system comprises a filter assembly ([0167]; Fig. 1B – see annotated figure below), TFF unit assembly ([0169]; Fig. 1B, ultrafiltration/dilution step), and a chromatography column ([0018]-[0019], [0131], [0135]; Fig. 1B, capture chromatography step), i.e., an enrichment module ([0134]-[0137] teach that the upstream steps removes impurities), the enrichment module comprises a TFF unit assembly and a chromatography column, i.e., a cell lysis buffer separation apparatus ([0135], TFF and column receive filtrate from fermentation harvest; [0014]-[0015], and [0133] teach that bacteria lyse during fermentation), and the cell lysis buffer separation apparatus comprises a TFF unit assembly, which uses a filtration membrane ([0135]), i.e., a filtration device.
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Ton does not explicitly disclose the filtration device being a multiplex – note: the claim language is interpreted according to BRI - filtration device, but discloses that TFF systems can use multiple membranes ([0181]). Thus, the TFF unit assembly meets the limitation.
Ton does not explicitly disclose the cell lysis buffer separation apparatus comprising a waste discharge pipeline, but teaches that the chromatography setups include outlets and associated tubing (i.e., pipeline) ([0172]) and that the capture column removes impurities ([0153]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a tube to an outlet of the chromatography column of the cell lysis buffer separation apparatus in the device disclosed by Ton to provide flow for impurities.
The preamble limitation “for preparing a polypeptide” is merely a recitation of a purpose or intended use of the invention and has been given an appropriate patentable weight (MPEP § 2111.02 II). The prior art system would be fully capable of achieving every claimed intended use because Ton teaches the system is capable of obtaining high potency, high yield botulinum neurotoxin (abstract).
Regarding claim 11, Ton teaches the system according to claim 10.
Ton further discloses wherein the system further comprises a fermentation module upstream of the enrichment module (Fig. 1B shows fermentation is upstream of enrichment).
The limitation “preferably, the fermentation module comprises a culture, fermentation, and lysis device of the host cell” is interpreted as optional structure (MPEP § 2173.05(d)).
Regarding claim 12, Ton teaches the system according to claim 10.
Ton further discloses wherein the system further comprises a purification module downstream of the enrichment module ([0138]-[0139]; Fig. 1B – see annotated figure above).
Regarding claim 13, Ton teaches the system according to claim 12.
Ton further discloses wherein the purification module comprises at least 1 chromatography device set ([0139] discloses multiple chromatography columns).
The limitation “preferably, the purification module comprises 3 chromatography device sets; preferably, the chromatography device is located in an isolator; preferably, the purification module further comprises a protease liquid supply device” is interpreted to be optional structure (MPEP § 2173.05(d)).
Regarding claim 14-15, such claims are directed to the intended use of the apparatus. The limitations drawn to the claimed polypeptide are directed to the intended use of the system of claim 10. It has been held that the intended manner of operating the claimed apparatus does not differentiate the claimed apparatus from the prior art apparatus because all structural limitations are taught in the prior art apparatus (MPEP § 2114 II). The apparatus taught by Ton would be fully capable of achieving every claimed intended use absent clear evidence to the contrary and absent a showing of unexpected results.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Ruegg (US Patent 9,469,849) discloses methods and systems for purifying non-complexed botulinum neurotoxin
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADRIAN J CARREON whose telephone number is (571)272-6818. The examiner can normally be reached Monday - Friday 8:30 AM - 5 PM.
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/A.J.C./ Examiner, Art Unit 1799
/William H. Beisner/ Primary Examiner, Art Unit 1799
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