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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
Claims 1-11,16, 17,19, 20, 22-23, 25, 27-30, 33-34, and 37-42 are pending in the instant application.
Priority
This application is a CON of abandoned Application 17/401093, filed on 8/12/2021 which claims priority to the provisional application 63/072673 filed on 8/31/2020 and 63/066077 filed on 8/14/2020.
Information Disclosure Statement
The information disclosure statements (IDS) dated 10/4/2023 and 11/19/2025 comply with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Objections to the Abstract
The abstract is objected to for lacking any mention of what the method comprises. Examiner recommends adding “using an anti-CD20 antibody” after the word “patient.”
Correction is required. See MPEP § 608.01(b).
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 24, para 0101; pg 44, para 0151; pg 58, para 0192; and pg 78, para 0247. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Objections to the Claims
Claim 1 is grammatically awkward, examiner recommends replacing “until from about 24 weeks from the initial dose” to “until at least 24 weeks after the initial dose”. Similarly, claims 2 and 6-7 also include the phrase “until from about [time] from the initial dose”. Please replace this phrase with the corresponding “until at least [time] after the initial dose”.
Claim 40 lacks a period at the end of the claim.
Correction is required. See MPEP § 608.01(m).
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.
Claims 1-11,16, 17,19, 20, 22-23, 25, 27-30, 33-34, and 37-41 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.
All except 42
The term “about” in claims 1-11, 17, 20, 23, and 25 is a relative term which renders the claim indefinite. The term “about” 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. The instant specification does not give any quantitative measure of determining about (instant specification pg 15, paragraph 0069). For example “about 1.2 grams” could include a breadth of 1-2 grams for one artisan, while another would assume that only variations of the hundredths place would be acceptable, such as 1.20-1.29 grams. Regarding claims 1-10, it is unclear what the metes and bounds of “about” 0.6, 1.2, or 1.8 grams are. Regarding claims 1, 2, 6, and 7, it is unclear what the metes and bounds of “about” 75 kg are. Regarding claims 1, 6, 17, 20, 23, and 25, it is unclear what the metes and bounds of “about” 24 weeks are. Regarding claims 2, 7, 17, 20, 23, 25, it is unclear what the metes and bounds of “about” 6 months are. Regarding claim 11, it is unclear what the metes and bounds of “about” x days are, where x is a specified range of values. As mentioned previously, the specifications fail to describe any quantitative guidelines for determining what “about” means. Dependent claims 16, 19, 22, 27-30, 33-34, and 37-41 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 3, 8, 11
Regarding claims 3, 8, and 11, it is unclear what the metes and bounds of a single “dose” comprises. Claims 3 and 8 describe two infusions comprising one dose, but does not give an interval of time between those infusions, thus it is impossible to determine if two infusions given on separate days constitutes one dose or two doses. Similarly, in claim 11, it is impossible to tell whether the “second infusion” constitutes part 2 of dose one or is the start of dose two.
Claim 38
Claim 38 contains the trademark/trade name Campath. 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 alemtuzumab and, accordingly, the identification/description is indefinite.
Claim 38
Claim 38 includes the limitation “and another B-cell surface marker antibody” at the end of a list which includes many medicaments (e.g. NSAIDs) which are not B-cell surface marker antibodies. It is unclear what “another” means in this context.
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.
Claim 38 is 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.
Claim 38
Claim 38 is drawn to “another B-cell surface marker antibody” wherein applicant lists over 20 different antigens (instant specification pg 10, paragraph 0047), but describes no antibody structure that would result in the binding of the described antigens. Applicant can meet the written description requirement by providing either (i) an exemplary number of species or (ii) the core structure responsible for the function of being a B-cell surface marker antibody. The specification as filed fails to provide an adequate written description of the genus “B-cell surface marker antibodies” because it fails to provide (i) or (ii). Even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity. Furthermore, note in the decision in Amgen v. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen.” Because applicant cannot describe said antibodies using an exemplary number of species, applicant must then disclose the core structure of these antibodies that is responsible for that function. Applicant has failed to described the binding region or even target of these antibodies, thus Applicant has failed to meet the written description requirement of “B-cell surface marker antibody”.
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.
Claim 42(1-11,16, 17,19, 20, 22-23, 25, 27-30, 33-34, and 37-41) is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Leppert (WO2017062682).
Claim 42
Regarding claim 42(1-11,16, 17,19, 20, 22-23, 25, 27-30, 33-34, and 37-41), Leppert teaches an article of manufacture comprising: (a) a container comprising an anti-CD20 antibody (e.g., ocrelizumab), a humanized antibody containing the VH and VL domains of instant SEQ ID NO: 8 and 7, respectively, with a human IgG1 chain constant region (pg 44, paragraph 0206); and (b) a package insert with written instructions for treating multiple sclerosis in a patient (pg 30, paragraph 0102). The sequence alignment for the VH of instant SEQ ID NO: 8 (Leppert SEQ ID NO: 8) is shown below.
instant_8 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY 60
Leppert_8 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY 60
************************************************************
instant_8 NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV 120
Leppert_8 NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV 120
************************************************************
instant_8 SS 122
Leppert_8 SS 122
**
The sequence alignment for the VL of instant SEQ ID NO: 7 (Leppert SEQ ID NO: 2) is shown below.
instant_7 DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR 60
Leppert_2 DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR 60
************************************************************
instant_7 FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKR 107
Leppert_2 FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKR 107
***********************************************
While the part (b) of claim 42 require specific instructions reciting methods of the previous claims, it should be noted that no functional relationship exists between these written instructions and the insert they are written on and therefore the printed matter is “owed no patentable weight.” See MPEP § 2111.05.
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 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 1-11, 16-17, 19-20, 22-23, 25, 27-30, 33-34, and 37-42 are rejected under 35 U.S.C. 103 as being unpatentable over Leppert as applied to claim 42 above, and further in view of Houtchens (doi: 10.1016/j.yfrne.2018.07.001). The previously mentioned teachings of Leppert in the 102 rejection above apply here as well.
Claim 1-2, 6-7
Regarding claims 1- 2 and 6-7, Leppert teaches a method of treating multiple sclerosis in a patient comprising administering about 0.3-4 grams of anti-CD20 antibody for the first dose, followed by another dose of about 0.3-4 grams of anti-CD20 antibody, wherein the period of time between the first and second dose is 16-60 weeks (pg 67, paragraph 0282). Furthermore, Leppert teaches the anti-CD20 antibody is Ocrelizumab, a humanized antibody containing the VH and VL domains of instant SEQ ID NO: 8 and 7, respectively (pg 28-29, paragraph 0097) including a human IgG1 constant region (human IgG1 chain constant region (pg 44, paragraph 0206).
Leppert is silent on the weight of the patient being more or less than 75 kg.
Houtchens teaches that adult females are about 68 kg and adult males are about 78 kg (pg 125, Table 1). Furthermore, Houtchens teaches that the majority of MS patients treated in clinical trials with Ocrelizumab are female (pg 128, Table 2). Thus the majority of patients treated for MS weigh less than 75 kg at the time of treatment.
Prior to the effective filing date of the claimed invention, one of ordinary skill in the art, seeking to design a dosage and treatment schedule for patients with MS that weigh less than 75 kg would have found it obvious to select an appropriate ocrelizumab dosage and dosage schedule from Leppert and apply the knowledge from Houtchens that the majority of patients weigh less than 75 kg, thus performing the routine optimization to arrive at the claimed dosage and dosage schedule for this population. Houtchens also teaches that patients that weigh 75 kg and over are also in need of treatment (pg 132, col 1, paragraph 4), thus it would have been obvious to use the methods in Leppert because Leppert teaches that this particular dosage and dosage schedule of ocrelizumab is effective in treating MS. In the instant case, the ocrelizumab dosage amounts and dosage schedules are anticipated by Leppert. Where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP § 2144.05 (I). In the instant case, Leppert’s dosage of about 0.3-4 grams of ocrelizumab overlaps with the instantly claimed dosages of about 0.6, 0.9, 1.2, and 1.8 grams. Therefore, the range in Leppert renders obvious the claimed range. Similarly, Leppert’s intervals between doses being between 1-20 days between infusions, 20-24 weeks between the 1st and 2nd dose, 22-40 weeks between the 2nd and 3rd dose, 10-29 weeks between the 3rd and 4th dose, and 20-30 weeks between subsequent doses given after the 4th overlaps with the instantly claimed intervals of about 3-17 days between infusions, about 24 weeks between the 1st and 2nd dose, about 24 weeks between the 2nd and 3rd dose, about 24 weeks between the 3rd and 4th dose, about 24 weeks between the 4th and 5th dose, and about 20-30 weeks between subsequent doses given after the 5th. Therefore, the range in Leppert also renders obvious the claimed range. One of ordinary skill in the art would have recognized that the particular dosage and dosage schedule that was most effective for a particular patient depends on a number of parameters unique to the patient, such as body weight. Thus, it was a matter of routine optimization to arrive at the instantly claimed dosages and dosage schedule of ocrelizumab for these patients. See MPEP § 2144.05 (II)(A).
Claim 3-5, 8-10
Regarding claims 3-5, and 8-10, Leppert teaches the anti-CD20 antibody can be administered intravenously (pg 70, paragraph 0295), in a dosage of 0.3-4 grams (pg 67, paragraph 0282), and in one example, Leppert teaches administering 0.6 g of ocrelizumab every 24 weeks (pg 104, paragraph 417).
Claim 11
Regarding claim 11, Leppert teaches that the period of time between anti-CD20 dose is between 1-20 days (pg 48, paragraph 0221).
Claim 16
Regarding claim 16, Leppert teaches an optional third dose of anti-CD20 antibody (pg 68, paragraph 0285).
Claim 17
Regarding claim 17, Leppert teaches that the third antibody dose is given 46-60 weeks after the first, wherein the interval between the first and second dosage is 20-24 weeks, thus gives an interval of 22-40 weeks between the second and third dosage (pg 68, paragraph 0285).
Claim 19
Regarding claim 19, Leppert teaches a fourth antibody dose (pg 68, paragraph 0287).
Claim 20
Regarding claim 20, Leppert teaches that the fourth antibody dose is given 70-75 weeks after the first, wherein the interval between the first and third dosage is 46-60 weeks, thus gives an interval of 10-29 weeks between the third and fourth dosage (pg 68, paragraph 0287).
Claim 22-23, 25
Regarding claim 22-23 and 25, Leppert teaches that additional antibody dosages beyond the fourth exposure may be administered, in which case the interval between the most recent antibody dosages is 20-30 weeks (pg 68, paragraph 0288).
Claim 27
Regarding claim 27, Leppert teaches the LC and HC of instant SEQ ID NO: 9 and 11, respectively, as these sequences are included in ocrelizumab (SEQ ID NO: 13 and 14). The light chain alignment is shown below.
instant_9 DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR 60
Leppert_13 DIQMTQSPSSLSASVGDRVTITCRASSSVSYMHWYQQKPGKAPKPLIYAPSNLASGVPSR 60
************************************************************
instant_9 FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKRTVAAPSVFIFPPS 120
Leppert_13 FSGSGSGTDFTLTISSLQPEDFATYYCQQWSFNPPTFGQGTKVEIKRTVAAPSVFIFPPS 120
************************************************************
instant_9 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL 180
Leppert_13 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL 180
************************************************************
instant_9 SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 213
Leppert_13 SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 213
*********************************
The heavy chain alignment is shown below.
instant_11 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY 60
Leppert_27 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSYNMHWVRQAPGKGLEWVGAIYPGNGDTSY 60
************************************************************
instant_11 NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV 120
Leppert_27 NQKFKGRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARVVYYSNSYWYFDVWGQGTLVTV 120
************************************************************
instant_11 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
Leppert_27 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
************************************************************
instant_11 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL 240
Leppert_27 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL 240
************************************************************
instant_11 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
Leppert_27 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
************************************************************
instant_11 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
Leppert_27 YNATYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIAATISKAKGQPREPQVYTLPPSR 360
**:********************************** *********************
instant_11 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
Leppert_27 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
************************************************************
instant_11 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 451
Leppert_27 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 451
*******************************
Claim 28
Regarding claim 28, Leppert teaches that the antibody is ocrelizumab (pg 100, paragraph 0405).
Claim 29
Regarding claim 29, Leppert teaches that the multiple sclerosis (MS) is relapsing multiple sclerosis (RMS) (pg 100, paragraph 0404).
Claim 30
Regarding claim 30, Leppert teaches wherein the treatment of the patients with RMS results in a delayed onset or reduced risk of 24-week confirmed disability improvement (claim 53).
Claim 33
Regarding claim 33, Leppert teaches that the MS is primary progressive multiple sclerosis (PPMS) (claim 133).
Claim 34
Regarding claim 34, Leppert teaches that ocrelizumab significantly reduced clinical disability progression sustained for 12 weeks and a reduction in T2 lesion volume in patients with PPMS (pg 152, paragraph 0536).
Claim 37
Regarding claim 37, Leppert teaches that another medicament may be administered after administering the first dose of anti-CD20 antibody (pg 71, paragraph 0297).
Claim 38
Regarding claim 38, Leppert teaches that the second medicament can be a chemotherapeutic agent, an immunosuppressive agent, a cytokine, an antibody, or a hormone (pg 71, paragraph 0297).
Claim 39-40
Regarding claims 39-40, Leppert teaches that in one embodiment, patients have not had prior treatment with any B-cell targeted therapy, such as ocrelizumab, and in another embodiment, patients did have prior treatment with a B-cell targeted therapy, such as ocrelizumab (pg 66, paragraph 0274).
Claim 41
Regarding claim 41, Leppert teaches that the anti-CD20 antibody may be the only drug administered to the patient (pg 71, paragraph 0297).
Relevant Prior Art
McCool (doi: 10.1016/j.msard.2018.12.040) teaches that 75% of MS patients in randomized controlled trials have relapsing MS, and that these individuals exhibit a superior response to ocrelizumab over Interferon-based therapies (abstract).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/
Supervisory Patent Examiner, Art Unit 1675
Prosecution Insights