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 .
RESPONSE TO APPLICANT’S AMENDMENT
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/07/25 has been hereby entered.
2. Claims 1, 3-7, 12, 13, 14,16-18, 20-46,48, 49-53 are pending.
Claims 48, 49 stand withdrawn from further consideration by the Examiner, 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions.
Claims 1, 3-7, 12, 13, 14,16-18, 20-46 and 50-53 read on a method for decreasing trisulfide bonds levels in a polypeptide, comprising culturing a host cell encoding the polypeptide with the basal medium as recited in claim 1 are under consideration in the instant application.
3. 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.
4. Claims 1, 3-7, 12, 13, 14,16-18, 20-46 and 50-53 stand rejected under 35 U.S.C. 103 as obvious over US Patent Application 20150267237, US Patent Application 20180346881 ,US Patent Application 20190194602 , US Patent Application 20180312811 and US Patent Application 20180251805, US Patent Application 20150274808, US Patent Application 20190144817 and US Patent Application 20170327786 in view of US Patent Application 20210017553 for the same reasons set forth in the previous Office Action, mailed on 11/07/24
Applicant’s arguments filed on 11/07/25 have been fully considered but have not been found convincing.
Applicant asserts that: as amended the claims now recited that a basal medium contains both methionine and cysteine at recited concentrations. US Patent Application 20180251805 and US Patent Application 20150274808 do not articulate said features. (ii) US Patent Application ‘553 teaches away from the claimed methionine ranges.
As initial matter it is noted that the Examiner disagrees with Applicant’s interpretation of the teaching of US Patent Application’ 808 and US Patent Application’805. In particular, US Patent Application’ 808 and US Patent Applicant each explicitly teach that the basal medium might contain either cysteine alone or methionine alone or combination of met+Cys ( see paragraphs 0156 and 0135 accordingly ).
As has been stated in the previous Office Action, it is the Examiner’s position that both US Patent Appication’805 and 808 explicitly stated that the present invention pertains to method of preventing and elimination trisulfide bonds in protein during culturing cells in the disclosed cell culture medium comprising methionine. Even if said references dose not explicitly disclosed the specific concentration of methionine as instantly claimed, said references were used to show that it was know to one skilled in the art that manipulating with the concentration of methionine in the culture medium results in removing or decreasing trisulfide bond levels in a polypeptide.
The Examiner reiterated his position that it would be conventional and within the skill of the art to determine an optimal concentration of methionine in the culture medium , for example between 1.0-2mM as taught by US Patent Application’553 to decrease trisulfide bond level in a polypeptide.
Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
As has been stated previously, US Patent Application’ 805 teaches a method of reducing the level of trisulfide bond in the polypeptide comprising culturing cells in cell in the basal culture medium comprising 150 M methionine and/or cystein. US Patent Application’ 805 teaches the use of mass spectrometry to measure the level of trisulfide bond ( see entire document, paragraphs 0058, 0091 0108 0149 in particular). In particular US Patent Application’ 805 teaches that in some embodiments, protein trisulfide bond formation is prevented, inhibited or curtailed via monitoring and/or manipulating the concentration of cysteine and/or cystine present in a cell culture media at or below a threshold level. For example, in order to decrease or maintain low cysteine and/or cystine levels, methionine can replace cysteine and/or cystine in a nutrient feed. It is the Examiner’s position that it would be immediately obvious to one skill in the art that US Patent Application’ 805 teaches the use of methionine for reducing trisulfide bond in the polypeptide.
US Patent Application’ 808 teaches a method of reducing the level of trisulfide bond in the polypeptide comprising culturing cells in cell in the basal culture medium comprising 150 M of methionine and/or cysteine. US Patent Application’ 808 teaches the use of mass spectrometry to measure the level of trisulfide bond . US Patent Application’ 805 explicitly teaches that the presence of methionine can reduce or remove trisulfide bonds ( see entire document, paragraphs 0073, 0114, 0136 in particular). US Patent Application’ 808 teaches that in some embodiments, protein trisulfide bond formation is prevented, inhibited or curtailed via monitoring and/or manipulating the concentration of cysteine and/or cystine present in a cell culture media at or below a threshold level. For example, in order to decrease or maintain low cysteine and/or cystine levels, methionine can replace cysteine and/or cystine in a nutrient feed. It is the Examiner’s position that it would be immediately obvious to one skill in the art that US Patent Application’ 808 teaches the use of methionine for reducing trisulfide bond in the polypeptide.
With regards to Applicant’s statement that “US Patent Application ‘553 teaches away from the claimed methionine ranges.”
A prior art reference may be considered to teach away when "a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant." In re Gurley , 27 F.3d 551, 553, 31 USPQ2d 1130, 1131 (Fed. Cir. 1994). General skepticism of those in the art -- not amounting to teaching away -- is also "relevant and persuasive evidence" of nonobviousness. Gillette Co. v. S.C. Johnson & Son, Inc. , 919 F.2d 720, 726, 16 USPQ2d 1923, 1929 (Fed. Cir. 1990). In effect, "teaching away" is a more pointed and probative form of skepticism expressed in the prior art. In any case, the presence of either of these indicia gives insight into the question of obviousness.
The instantly claimed range concentration of methionine is between 1.58 and about 2.25mM
Methionine.
US Patent Application 20210017553 teaches a method of culturing cell producing polypeptide, such as CHO in the basal culture medium comprising methionine at concentration between 05-2 mM of methionine ( see entire document, paragraphs 0033, 0040,0134,0146.) US Patent Application 20210017553 explicitly teaches that in the preferred embodiment the concentration of methionine is maintained between 0.1 to 2mM in cell culture medium ( emphases added, see paragraph 0146 in particular).
It is the Examiner’s position that it would be immediately obvious to one skill in the art that US Patent Application ‘553 does not teaches away from the claimed range between 1.58 and about 2.25mM.
It is noted that US Patent Application’553 does not explicitly teaches decreasing trisulfide bond levels in the polypeptide. However, said functional limitation would be an inherent properties of the referenced basal medium comprising between 1 and 2 mM methionine, because the reference concentration of methionine in basal medium is the same as instantly claimed. If the prior art structure is capable of performing the intended use, then it meets the claim. For example in Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999); the following was noted. “Artisans of ordinary skill may not recognize the inherent characteristics or functioning of the prior art. However, the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. “ The Court further held that “this same reasoning holds true when it is not a property but an ingredient which is inherently contained in the prior art”. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
It is the Examiner position that it would be conventional and within the skill of the art to use the determine an optimal concentration of methionine in the culture medium , for example between 1-2mM as taught by US Patent Application’553.
Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
US Patent Application’ 817 teaches a method for producing polypeptide comprising culturing cell in the basal culture medium comprising about 10 mM of hypotaurine and/ or methionine( see entire document, paragraphs 0005, 0007, 0008, 0153 and Table 4 in particular)
US Patent Application’ 786 teaches a method for producing polypeptide comprising culturing cell in the basal culture medium comprising about 10 mM of hypotaurine and/ or methionine( see entire document, paragraphs 0001, 0010, in particular).
Application’ 237 teaches a method for producing polypeptide comprising culturing CHO cell in the basal culture medium comprising iron and or vitamin B12 or vitamin B2 . US Patent Application’ 237 teaches that the iron concentration is between 2 uM to about 80 uM, vitamin B12 concentration is between 0.05 mg/L to about 2.r mg/L. US Patent Application’ 237 teaches that said basal culture medium comprising cysteine. US Patent Application’ 237 teaches that said basal culture medium comprising chelating agent such as EDTA ( see entire document, paragraphs 0010, 0014, 0015, 0132, 0168 in particular).
US Patent Application’ 881 teaches a method for producing polypeptide comprising culturing CHO cell in the basal culture medium comprising iron and/ or vitamin B12, methionine. ( see entire document, paragraphs 0019, 0020, 0023 in particular).
US Patent Application’ 602 teaches a method for producing polypeptide comprising culturing CHO cell in the basal culture medium comprising iron, and or vitamin of group B, for example vitamin B12 ( see entire document, paragraphs 0005, 0128, 0134, in particular).
US Patent Application’ 811 teaches a method for producing polypeptide comprising culturing CHO cell in the basal culture medium comprising iron, and or vitamin of group B, for example vitamin B12, methionine , cysteine and chelating agent such as EDTA ( see entire document, paragraphs 0005, 0008, 0049, 0065, 0107 and claims in particular).
From the combined teaching of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
5. All claims are either identical to or patentably indistinct from claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114.
Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no, however, event will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
6. No claims is allowed.
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michail Belyavskyi whose telephone number is 571/272-0840. The examiner can normally be reached Monday through Friday from 9:00 AM to 5:30 PM. A message may be left on the examiner's voice mail service. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch can be reached on 571/ 272-8149
The fax number for the organization where this application or proceeding is assigned is 571/273-8300
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/MICHAIL A BELYAVSKYI/Primary Examiner, Art Unit 1644