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 .
Support for the amendments is within the instant application specification.
Applicant’s amendment to the claims filed on 5/12/2026 in response to the Non-Final Rejection mailed on 2/13/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-7, 9-16, 18 are pending
Claims 8, 17 are cancelled.
Applicant’s remarks filed on 5/12/2026 in response to the Non-Final Rejection mailed on 2/13/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Withdrawn Rejections
The rejection of claims 1-9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment of claim 1 to define the recitation ‘related substances’ and cancellation of claims 8, 17.
The rejection of claims 1-18 under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more modifications is withdrawn in view of Applicant’s amendment of claim 1 to delete the recitation ‘an analysis,’ and cancellation of claims 8, 17.
The rejection of claims 8, 17 under 35 U.S.C. 103 as being unpatentable over Mant et al (2007, Methods in Molecular Biology, cited on PTO-892 dated 2/13/2026) {herein Mant} as evidenced by Agilent wavelength (2025, Marshall Scientific, cited on PTO-892 dated 2/13/2026) {herein Agilent Wavelength is withdrawn in view of Applicant’s cancellation of claims 8,17.
Priority
Acknowledgement is made of this national stage entry of Continuation of PCT/CN2023/093879 of Non-provisional Application No. 18/591,010, filed on 5/12/2023, which claims foreign priority under 35 U.S.C. 119(a)-(d) to Chinese Patent Application No. CN202210921653.8, filing date 8/2/2022. The certified copy has been filed in the present application on 4/12/2021.
New Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/26/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Maintained 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.
The rejection of claims 10-16, 18 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 is maintained. The rejection has been modified in view of Applicant’s amendment of claim 10 to recite ‘to monitor an impurity content in the eye drop formulation containing germinal peptide.’
Regarding claim 10 (claims 11-16, 18 dependent thereof), the recitation of the amended phrase ‘to monitor an impurity content in the eye drop formulation containing germinal peptide’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally and functionally. It is unclear what the phrase ‘to monitor an impurity content in the eye drop formulation containing germinal peptide’ is intended to encompass as there are an indefinite number of ways one can ‘monitor’ an impurity content.. Without a specific quantitative definition as to what is encompassed in the term “monitoring” one of skilled cannot determine what encompasses the “monitoring” method within the instant application. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase.
Maintained 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The rejection of claims 1-7, 9 under 35 U.S.C. 103 as being unpatentable over Mant et al (2007, Methods in Molecular Biology, Examiner cited) {herein Mant} in view of EP3342398A1 (Date Published: 4/7/2018, cited on IDS dated 3/26/2026) {herein ‘398} as evidenced by Agilent wavelength (2025, Marshall Scientific, cited on PTO-892 dated 2/13/2026) {herein Agilent Wavelength}, Hannappel et al (Date of Publication: 2007, Institute of Biochemistry, Examiner cited) {herein Hannappel} are maintained. The rejection has been modified in view of Applicant’s amendment of claim 1 to recite ‘A method for separating germinal peptide from related substances in a germinal peptide preparation, comprising the following steps: (1) preparing a sample of the germinal peptide preparation; and (2) separating germinal peptide from related substances in the sample by high-performance liquid chromatography, wherein the related substances comprise one or more selected from Glu7- germinal peptide, D-Leu 1 -germinal peptide, and Di-Glu5-germinal peptide; a chromatographic column with octadecylsilane-bonded silica gel as a packing is adopted for the high-performance liquid chromatography; and mobile phases for the high-performance liquid chromatography comprise a mobile phase A and a mobile phase B, wherein the mobile phase A is a trifluoroacetic acid aqueous solution with a volume ratio of the trifluoroacetic acid to water being 0.05:100 to 0.15:100, and the mobile phase B is trifluoroacetic acid-acetonitrile; and wherein the high-performance liquid chromatography adopts a gradient elution as follows: 0 min: a volume ratio of the mobile phase A to the mobile phase B is 100:0; 8 min: the volume ratio of the mobile phase A to the mobile phase B is 83:17 to 87:13; 8 min to 13 min: the volume ratio of the mobile phase Ato the mobile phase B is 83:17 to 87:13; and 13 min to 20 min: the volume ratio of the mobile phase A to the mobile phase B is 100:0.’
Claims 1-7, 9 are drawn to a method for separating germinal peptide from related substances in a germinal peptide preparation, comprising the following steps: (1) preparing a sample of the germinal peptide preparation; and (2) separating germinal peptide from related substances in the sample by high-performance liquid chromatography, wherein the related substances comprise one or more selected from Glu7- germinal peptide, D-Leu 1 -germinal peptide, and Di-Glu5-germinal peptide; a chromatographic column with octadecylsilane-bonded silica gel as a packing is adopted for the high-performance liquid chromatography; and mobile phases for the high-performance liquid chromatography comprise a mobile phase A and a mobile phase B, wherein the mobile phase A is a trifluoroacetic acid aqueous solution with a volume ratio of the trifluoroacetic acid to water being 0.05:100 to 0.15:100, and the mobile phase B is trifluoroacetic acid-acetonitrile; and wherein the high-performance liquid chromatography adopts a gradient elution as follows: 0 min: a volume ratio of the mobile phase A to the mobile phase B is 100:0; 8 min: the volume ratio of the mobile phase A to the mobile phase B is 83:17 to 87:13; 8 min to 13 min: the volume ratio of the mobile phase Ato the mobile phase B is 83:17 to 87:13; and 13 min to 20 min: the volume ratio of the mobile phase A to the mobile phase B is 100:0.
With respect to claims 1-3, 6, 9, Mant teaches a method wherein short peptide samples (5aa to 20aa) are separated using an Agilent HPLC column (page 11, para 2, page 14, para 2). Mant further teaches the HPLC column is packed with silica-based supports containing octadecyl (page 11, para 2). Mant further teaches the mobile phases are carried out using aqueous trifluoroacetic acid and acetonitrile systems (page 11, para 2) which are the same as the recited mobile phase A and mobile phase B, respectively (instant application claim 1). Said column is run at a linear AB gradient (1% CH3CN/min for 30 min, followed by 0.1% CH3CN/min for 150 min, followed by 1% CH3CN/min for 30 min) at a flow rate of 2 mL/min and room temperature, where eluent A is 0.2% aqueous TFA, pH 2, and eluent B is 0.2% TFA in CH3CN (page 42, #4). Although the reference of Mant does not explicitly teach the limitations of claim 1 (wherein the high-performance liquid chromatography adopts a gradient elution as follows: 0 min: a volume ratio of the mobile phase A to the mobile phase B is 100:0; 8 min: the volume ratio of the mobile phase A to the mobile phase B is 83:17 to 87:13; 8 min to 13 min: the volume ratio of the mobile phase A to the mobile phase B is 83:17 to 87:13; and 13 min to 20 min: the volume ratio of the mobile phase A to the mobile phase B is 100:0), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the ratios of mobile phases A and B depending on the particular application. It would be routine for one to arrive at the volume ratio for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious. Additionally, although the reference of Mant does not explicitly teach the limitations of claim 2 (wherein a volume ratio of trifluoroacetic acid to acetonitrile in the mobile phase B is 0.05:100 to 0.15:100), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the volume ratio of trifluoroacetic acid to acetonitrile in the mobile phase B depending on the particular application. It would be routine for one to arrive at the volume ratio for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
Mant further teaches a method wherein the HPLC column is run at room temperature (page 40, #2). Although the reference of Mant does not explicitly teach the limitations of claim 3 (wherein a column temperature of the chromatographic column is 30°C to 40°C), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the temperature of the column depending on the particular application. It would be routine for one to arrive at the temperature for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
With respect to claim 4, Mant teaches a method wherein the synthetic crude peptide is applied (100 mg and 200 mg sample amounts) to an HPLC column (Column 9 on Instrument 3) (page 42, #4). Although the reference of Mant does not explicitly teach the limitations of claim 4 (wherein an injection volume for the high-performance liquid chromatography is 90 μL to 110 μL), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the injection volume for the high-performance liquid chromatography depending on the particular application. It would be routine for one to arrive at the injection volume for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
With respect to claim 5, Mant teaches a method wherein short peptide samples (5aa to 20aa) are separated using an Agilent HPLC column (page 11, para 2, page 14, para 2). Evidentiary reference of Agilent Wavelength is cited to demonstrate that the range at which the HPLC column can detect protein is 190nm – 950nm (page 2). As such, absent evidence otherwise, it is the Examiner’s position that a wavelength of 210 nm, as recited in claim 5 of the instant application would be detected. Said method is also able to remove contaminants from the sample (page 48, para 2), thereby improving the quality of the sample.
With respect to claim 7, Mant teaches a method wherein columns are no longer than 250mm and no larger diameters than 10mm ID, avoiding the prohibitively expense scale-up costs
in terms of equipment, larger columns and solvent consumption (page 40, para 2). Although the reference of Mant does not explicitly teach the limitations of claim 7 (wherein the chromatographic column has a specification of 4.6 × 150 mm, 3 μm), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the specification of the chromatographic column depending on the particular application. It would be routine for one to arrive at the specification of the column for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
With respect to claim 9, Mant teaches to design the gradient method, a “rule of thumb” has been developed (page 42, #4). The researcher determines the percentage acetonitrile required to elute the peptide of interest by running the crude peptide on an analytical column at 1% CH3CN per min (page 42, #4). In the present case, the peptide of interest is eluted at 42% CH3C(page 42, #4). To establish the percentage CH3CN at which the 0.1% CH3CN gradient begins, the rule of thumb is to start 12% below that required to elute the peptide in the 1% gradient run. Thus, the gradient for the preparative run is 0 to 30% acetonitrile at 1% acetonitrile/min (30% is 12% below 42%), then begin the gradient of 0.1% CH3CN per min for 150 min (increase of 15% CH3CN) followed by 1% CH3CN per min for 30 min to wash the remaining hydrophobic impurities off the column (page 42, #4). Although the reference of Mant does not explicitly teach the limitations of claim 9 (a gradient elution as follows: 0 min: a volume ratio of the mobile phase A to the mobile phase B is 100:0; 8 min: the volume ratio of the mobile phase A to the mobile phase B is 85:15; 8 min to 13 min: the volume ratio of the mobile phase A to the mobile phase B is 85:15; and 13 min to 20 min: the volume ratio of the mobile phase A to the mobile phase B is 100:0), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the gradient elution depending on the particular application. It would be routine for one to arrive at the gradient elution for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
However, Mant does not teach a method of separating germinal peptide from related substances in a germinal peptide preparation (claim 1).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to successfully separate any peptides that fall within the range of 5-10 amino acids from its related substances including that of germinal peptides from related substances comprising one or more peptides selected from Glu7- germinal peptide, D-Leu 1 -germinal peptide, and Di-Glu5-germinal peptide as Mant teaches a method wherein short peptide samples (5aa to 20aa) are purified using an Agilent HPLC column (page 11, para 2, page 14, para 2). It is well-known in the art that germinal peptides are comprised of 7 amino acids (LKKTETQ). As such, it would be obvious to one of ordinary skilled in the art that said peptide would be effectivity and efficiently separate using an HPLC column. Especially since Mant teaches an HPLC column that is able to separate peptides as small at 5 amino acids.
One of ordinary skill in the art would be motivated to utilize the method taught by Mant for the separation of germinal peptides from related substances comprising one or more selected from Glu7- germinal peptide, D-Leu 1 -germinal peptide, and Di-Glu5-germinal peptide as Mant teaches the separation of short peptides (4 aa – 20 aa) (figure 2) using HPLC provides excellent resolution (page 16, para 1). Supporting the Examiner’s position is the evidentiary reference of Hannappel which is cited to demonstrate that HPLC is routinely utilized for separation and quantitation of Thymosin Beta 4-like peptides, of which are germinal peptides since germinal peptides are derived from Thymosin Beta 4. Furthermore, said method reduces the number of contaminants in a sample (page 13, para 1) through selective separation, thereby resulting in a better quality sample that can be more readily utilized in therapeutic studies. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Beginning on p. 12 of Applicant’s remarks dated 5/12/2026, in summary, Applicant contends that currently amended, independent claim 1 recites an additional element that is not taught in the combined prior art references. Claim 1 now requires separating germinal peptide from related substances in a germinal peptide preparation. Applicant contends that the disclosure in Mant (or Agilent Wavelength) is silent on teaching these specific related substances, or to any disclosure of germinal peptide. Applicant contends that the Examiner relies on an assumption that Mant's disclosure of short peptides and peptide separations means Mant teaches "related substances in a germinal peptide preparation," stating that "related substances could be small peptides of 7 amino acids etc." Applicant respectfully submits that this statement is not a prior-art disclosure. Further, a general teaching that short peptides may be analyzed by HPLC does not disclose or suggest the specifically claimed germinal-peptide impurities or the claimed separation of germinal peptide from those impurities.
The arguments are not persuasive. Examiner contends that reason to show obviousness need not be the same as that of the Applicant’s reason. MPEP 2144.IV states “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991).” In addition, Mant teaches a method wherein short peptide samples (5aa to 20aa) are purified using HPLC (page 11, para 2, page 14, para 2). Since germinal peptides are comprised of 7 amino acids (LKKTETQ), Examiner contends that it would be obvious to one of ordinary skilled in the art to apply the known technique of the separation of any type of small peptides by HPLC including germinal peptides to yield the predictable result of the separation of germinal peptides from related substances. Especially since Mant teaches an HPLC column that is able to separate peptides as small at 5 amino acids, of which germinal peptides are comprised of 7 amnio acids. Additionally, it is well-known in the art that High-Performance Liquid Chromatography (HPLC) is the gold standard for reliably separating mixed with major compounds. Supporting the Examiner’s position is the evidentiary reference of ams which is cited to demonstrate that HPLC is the gold standard for impurity analysis and is capable of separating trace impurities (Evidentiary Reference: ams (Date of Publication: 9/22/2025, biopharma, Examiner cited) {herein ams). 2143.I.D. states “The rationale to support a conclusion that the claim would have been obvious is that a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art. One of ordinary skill in the art would have been capable of applying this known technique to a known device (method, or product) that was ready for improvement and the results would have been predictable to one of ordinary skill in the art.” As such, it is the Examiner’s position that applying the known technique of the separation of small peptides (5aa-20aa) to the separation of germinal peptide from related substances would have been obvious to one of ordinary skill in the art to yield predictable results.
Applicant submits that the claimed invention as a whole is not obvious based on the cited references because the limitations of separating germinal peptide from the related substances under the specifically recited HPLC conditions and gradient program is not taught in the combined prior art references.
The arguments are not persuasive. Examiner contends that Mant teaches a method wherein the column is ran at a linear AB gradient (1% CH3CN/min for 30 min, followed by 0.1% CH3CN/min for 150 min, followed by 1% CH3CN/min for 30 min) at a flow rate of 2 mL/min and room temperature, where eluent A is 0.2% aqueous TFA, pH 2, and eluent B is 0.2% TFA in CH3CN (page 42, #4). Examiner maintains that although the reference of Mant does not explicitly teach the limitations of claim 1 (formerly cancelled claim 8) (wherein the high-performance liquid chromatography adopts a gradient elution as follows: 0 min: a volume ratio of the mobile phase A to the mobile phase B is 100:0; 8 min: the volume ratio of the mobile phase A to the mobile phase B is 83:17 to 87:13; 8 min to 13 min: the volume ratio of the mobile phase A to the mobile phase B is 83:17 to 87:13; and 13 min to 20 min: the volume ratio of the mobile phase A to the mobile phase B is 100:0), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the ratios of mobile phases A and B depending on the particular application. It would be routine for one to arrive at the volume ratio for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
New Claim Rejections - 35 USC § 103
Claims 10-16, 18 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mant et al (2007, Methods in Molecular Biology, Examiner cited) {herein Mant} in view of EP3342398A1 (Date Published: 4/7/2018, cited on IDS dated 3/26/2026) {herein ‘398} as evidenced by Agilent wavelength (2025, Marshall Scientific, cited on PTO-892 dated 2/13/2026) {herein Agilent Wavelength}, Hannappel et al (Date of Publication: 2007, Institute of Biochemistry, Examiner cited) {herein Hannappel} and ams (Date of Publication: 9/22/2025, biopharma, Examiner cited) {herein ams}. The new rejection is necessitated by Applicant’s amendment of claim 10 to recite ‘a method for controlling quality of an eye drop formulation containing germinal peptide, comprising using the method according to claim 1 to monitor an impurity content in the eye drop formulation containing germinal peptide.’
Claims 10-16, 18 are drawn to a method for controlling quality of an eye drop formulation containing germinal peptide, comprising using the method according to claim 1 to monitor an impurity content in the eye drop formulation containing germinal peptide.
The teachings of Mant as applied to claims 1-7, 9 are set forth in the 103 rejection above.
With respect to claims 11, 16, Mant teaches a method wherein short peptide samples (5aa to 20aa) are separated using an Agilent HPLC column (page 11, para 2, page 14, para 2). The mobile phases are carried out using aqueous trifluoroacetic acid and acetonitrile systems (page 11, para 2) which are the same as the recited mobile phase A and mobile phase B, respectively (instant application claim 1). Although the reference of Mant does not explicitly teach the limitations of claim 11 (wherein a volume ratio of trifluoroacetic acid to acetonitrile in the mobile phase B is 0.05:100 to 0.15:100), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the volume ratio of trifluoroacetic acid to acetonitrile in the mobile phase B depending on the particular application. It would be routine for one to arrive at the volume ratio for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
With respect to claim 12, Mant teaches a method wherein the HPLC column is ran at room temperature (page 40, #2). Although the reference of Mant does not explicitly teach the limitations of claim 12 (wherein a column temperature of the chromatographic column is 30°C to 40°C), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the temperature of the column depending on the particular application. It would be routine for one to arrive at the temperature for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
With respect to claim 13, Mant teaches a method wherein the synthetic crude peptide is applied (100 mg and 200 mg sample amounts) to an HPLC column (Column 9 on Instrument 3) (page 42, #4). Although the reference of Mant does not explicitly teach the limitations of claim 13 (wherein an injection volume for the high-performance liquid chromatography is 90 μL to 110 μL), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the injection volume for the high-performance liquid chromatography depending on the particular application. It would be routine for one to arrive at the injection volume for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
With respect to claim 14, Mant teaches a method wherein short peptide samples (5aa to 20aa) are separated using an Agilent HPLC column (page 11, para 2, page 14, para 2). Evidentiary reference of Agilent Wavelength is cited to demonstrate that the range at which the HPLC column can detect protein is 190nm – 950nm (page 2). As such, absent evidence otherwise, it is the Examiner’s position that a wavelength of 210 nm, as recited in claim 14 of the instant application would be detected. Said method is also able to remove contaminants from the sample (page 48, para 2), thereby improving the quality of the sample.
With respect to claim 18, Mant teaches to design the gradient method, a “rule of thumb” has been developed (page 42, #4). The researcher determines the percentage acetonitrile required to elute the peptide of interest by running the crude peptide on an analytical column at 1% CH3CN per min (page 42, #4). In the present case, the peptide of interest is eluted at 42% CH3C(page 42, #4). To establish the percentage CH3CN at which the 0.1% CH3CN gradient begins, the rule of thumb is to start 12% below that required to elute the peptide in the 1% gradient run. Thus, the gradient for the preparative run is 0 to 30% acetonitrile at 1% acetonitrile/min (30% is 12% below 42%), then begin the gradient of 0.1% CH3CN per min for 150 min (increase of 15% CH3CN) followed by 1% CH3CN per min for 30 min to wash the remaining hydrophobic impurities off the column (page 42, #4). Although the reference of Mant does not explicitly teach the limitations of claim 18 (a gradient elution as follows: 0 min: a volume ratio of the mobile phase A to the mobile phase B is 100:0; 8 min: the volume ratio of the mobile phase A to the mobile phase B is 85:15; 8 min to 13 min: the volume ratio of the mobile phase A to the mobile phase B is 85:15; and 13 min to 20 min: the volume ratio of the mobile phase A to the mobile phase B is 100:0), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the gradient elution depending on the particular application. It would be routine for one to arrive at the gradient elution for the application they intend on using the germinal peptide preparation. Therefore, the above invention would have been prima facie obvious.
However, Mant does not teach the method of claim 10 for controlling quality of an eye drop formulation containing germinal peptide, comprising using the method according to claim 1 to monitor an impurity content in the eye drop formulation containing germinal peptide (claim 10).
With respect to claim 10, ‘398 teaches a method wherein HPLC is used to monitor purity changes in samples of ophthalmic preparations (para 0033).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply the teachings of Mant et al of a method wherein short peptide samples (5aa to 20aa) are separated using an Agilent HPLC column (page 11, para 2, page 14, para 2) or combine the teaching of ‘398 of a method wherein HPLC is used to monitor purity changes in samples of ophthalmic preparations (para 0033 and 0038).
One of ordinary skill in the art would be motivated to utilize the method taught by Mant of the separation of germinal peptides from related substances using HPLC in view ‘398 to monitor the purity of eye drop formulations containing germinal peptides as it is well-known in the art that High-Performance Liquid Chromatography (HPLC) is the gold standard for monitoring impurities because it reliably separates, identifies, and measures trace contaminants mixed with major compounds. Supporting the Examiner’s position is the evidentiary reference of ams which is cited to demonstrate that HPLC is the gold standard for impurity analysis and is capable of separating trace impurities (page 3, para 2). As such, it would be obvious to one of ordinary skill in the art that said method would allow for one to control the quality of an eye drop formulation containing germinal peptide by using the methods taught by Mant, in view of ‘398 as one would expect said methods to result in the detection of even trace amounts of impurities. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: This argument is found to be moot in view of the new rejection. Examiner contends that Mant in view of ‘938 teaches a method for controlling quality of an eye drop formulation containing germinal peptide, comprising using the method according to claim 1 to monitor an impurity content in the eye drop formulation containing germinal peptide.
Conclusion
Status of Claims
Claims 1-7, 9-16, 18 are pending
Claims 8, 17 are cancelled.
Claims 1-7, 9-16, 18 are rejected.
No claims are in condition for allowance.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERICA NICOLE JONES-FOSTER/ Examiner, Art Unit 1656
/MANJUNATH N RAO/ Supervisory Patent Examiner, Art Unit 1656
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